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221 Patel, S. R., et al. (2004). “Two epidemics: are we getting fatter as we sleep less?” Sleep 27:602–603.

222 Patel, S. R., et al (2006). “Association between reduced sleep and weight gain in women.” Am J Epidemiol 164:947–954.

223 Hasler, G., et al. (2004). “The association between short sleep duration and obesity in young adults: a 13-year prospective study.” Sleep 27:661–666.

224 Sekine, M., et al. (2002). “A dose–response relationship between short sleeping hours and childhood obesity: results of the Toyama Birth Cohort Study.” Child Care Health Dev 28:163–170.

225 Taheri, S., et al. (2004). “Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index.” PLoS Med 1:e62.

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228 Spiegel, K., et al. (2004). “Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin.” J Clin Endocrinol Metab 89:5762–5771.

229 Goyenechea, E., et al. (2006). "Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and peroxisome-proliferator-activated-receptor-2 gene polymorphisms." British Journal of Nutrition 96(05):965-972.

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271 Kadi, F., et al. (2008). "The Effects of Regular Strength Training on Telomere Length in Human Skeletal Muscle." Med Sci Sports Exerc 40(1): 82-87.

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275 Irie, M., et al. (2001). “Relationships between perceived workload, stress and oxidative DNA damage.” Int Arch Occup Environ Health 74(2):153-157.

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292 Deschauer, M., et al. (2006). "Novel Mitochondrial Transfer RNAPhe Gene Mutation Associated With Late-Onset Neuromuscular Disease." Arch Neurol 63(6):902-905.

293 Pistilli, E. E., et al. (2008). "Interleukin-15 and interleukin-15R[alpha] SNPs and associations with muscle, bone, and predictors of the metabolic syndrome." Cytokine 43(1):45-53.

294 Riechman, S. E., et al. (2004). "Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses." J Appl Physiol 97(6): 2214-2219.

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298 Schulze, J. J., et al. (2008). "Doping Test Results Dependent on Genotype of Uridine Diphospho-Glucuronosyl Transferase 2B17, the Major Enzyme for Testosterone Glucuronidation." J Clin Endocrinol Metab 93(7):2500-2506.

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301 W. P. T., et al. (2000). “Effect of sibutramine on weight maintenance after weight loss: a randomised trial.” Lancet 356:2119–2125.

302 Finer, N., et al. (2000). “Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study.” Diabetes Obes Metab 2:105–112.

303 Wadden, T. A., et al. (2001). “Benefits of lifestyle modification in the pharmacological treatment of obesity: a randomized trial.” Arch Intern Med 161:218–227.

304 Grudell, A. B., et al. (2008). “A controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese or overweight adults.” Gastroenterology 135(4):1142–1154.

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306 Potoczna, N., et al. (2004). "Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity." Journal of Gastrointestinal Surgery 8(8):971-982.

307 Christine, P., et al. (2005). "Relationship between Single Nucleotide Polymorphisms in Leptin, IL6 and Adiponectin Genes and their Circulating Product in Morbidly Obese Subjects before and after Gastric Banding Surgery." Obesity Surgery 15:11-23.

308 Chen, H. H., et al. (2007). "Ala55Val Polymorphism on UCP2 Gene Predicts Greater Weight Loss in Morbidly Obese Patients Undergoing Gastric Banding." Obesity Surgery 17(7):926-933.

Chapter Six
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310 Nonacs, P. (2007). "Social heterosis and the maintenance of genetic diversity." Journal of Evolutionary Biology 20(6):2253-2265.

311 Vellend, M. (2006). “The consequences of genetic diversity in competitive communities.” Ecology 87:304–311.

312 Rhodes, G., et al. (2005). "Attractiveness of own-race, other-race, and mixed-race faces." Perception 34(3):319-340.

313 Kalick, S. M., et al. (1998) “Does human facial attractiveness honestly advertise heath? Longitudinal data on an evolutionary question” Psychological Science 9:8-13.

314 Appel, J. (2009). “Mandatory Genetic Testing isn't Eugenics, it's Smart Science.” www.opposingviews.com.

315 Sagi, M., et al. (2009). "Preimplantation genetic diagnosis for BRCA1/2 - a novel clinical experience." Prenatal Diagnosis 29(5):508-513.

316 Hathaway, F., et al. (2009). "Consumers’ Desire towards Current and Prospective Reproductive Genetic Testing." Journal of Genetic Counseling 18(2):137-146.

317 Geifman-Holtzman, O. et al. (2008). "Prenatal diagnosis: update on invasive versus noninvasive fetal diagnostic testing from maternal blood." Expert Review of Molecular Diagnostics 8(6):727-751.

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319 Vennemann, M. M., et al. (2009). "Does Breastfeeding Reduce the Risk of Sudden Infant Death Syndrome?" Pediatrics 123(3):e406-410.

320 Mortensen, E. L., et al. (2002). "The Association Between Duration of Breastfeeding and Adult Intelligence." JAMA 287(18):2365-2371.

321 Caspi, A., et al. (2007). "Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism." Proceedings of the National Academy of Sciences 104(47):18860-18865.

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323 (2009). “Sperm bank sued under product liability law.” New Scientist. 2703:4.

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325 Jones, J. (2008). “Adoption experiences of women and men and demand for children to adopt by women ages 18-44 in the United States, 2002.” National Center for Health Statistics. Vital Health Stat 23(27).

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328 Coumans, A. B., et al. (1999). “Haemostatic and metabolic abnormalities in women with unexplained recurrent abortion.” Hum Reprod 14:211–214.

329 Brenner, B., et al. (1999). “Thrombophilic polymorphisms are common in women with fetal loss without apparent cause.” Thromb Haemost 82:6–9.

330 Coulam, C. B., et al. (2009). "Thrombophilic gene polymorphisms are risk factors for unexplained infertility." Fertility and Sterility 91(4, Supplement 1):1516-1517.

331 Ozcan, T., et al. (2001). “Genetic thrombophilia and thromboembolic complications.” Am J Obstet Gynecol 184:S189.

332 Nelen, W., et al. (1998). "Methylenetetrahydrofolate Reductase Polymorphism Affects the Change in Homocysteine and Folate Concentrations Resulting from Low Dose Folic Acid Supplementation in Women with Unexplained Recurrent Miscarriages." J Nutr 128(8):1336-1341.

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334 Nelen, W. L., et al. (1997). “Genetic risk factor for unexplained recurrent early pregnancy loss.” Lancet 350:861.

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337 Poongothai, J., (2009). “Genetics of human male infertility.” Singapore Med J 50(4): 336-47.

338 Aston, K. I., et al. (2009). "Genome-wide Study of Single Nucleotide Polymorphisms Associated with Azoospermia and Severe Oligozoospermia." J Androl 30(6):711-25.

339 Sun, C., et al. (1999). "An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y." Nat Genet 23(4):429-432.

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341 Miyagawa, Y., et al. (2005). "Single-Nucleotide Polymorphisms and Mutation Analyses of the TNP1 and TNP2 Genes of Fertile and Infertile Human Male Populations." J Androl 26(6):779-786.

342 Shady, A. A., Colby, B. R., et al. (2002). “Congenital erythropoietic porphyria: identification and expression of eight novel mutations in the uroporphyrinogen III synthase gene.” Br J Haematol 117(4):980-987.

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344 Sotos, J. G. (2008). “The Physical Lincoln Complete.” CreateSpace.

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Chapter Seven
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348 Butz, A. M., et al. (1993). "Newborn identification. Compliance with AAP guidelines for perinatal care." Clin Pediatr (Phila). 32(2):111-3.

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421 Olson, R. K. (2002). "Dyslexia: nature and nurture." Dyslexia 8:143–59.

422 Meng, H., et al. (2005). "DCDC2 is associated with reading disability and modulates neuronal development in the brain." Proc Natl Acad Sci U S A 102:17053–8.

423 Schumacher, J., et al. (2006). “Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.” Am J Hum Genet 78:52–62.

424 Deffenbacher, K. E., et al. (2004). “Refinement of the 6p21. 3 quantitative trait locus influencing dyslexia: linkage and association analyses.” Hum Genet 115:128–38.

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427 Cope, N., et al. (2005). “Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia.” Am J Hum Genet 76:581–91.

428 Francks, C., et al. (2004). “A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States.” Am J Hum Genet 75:1046–58.

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434 Nathoo, N., et al. (2003). "Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E." Mol Pathol 56(3):132-136.

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444 Schwarz, A. “Silence on Concussions Raises Risks of Injury.” The New York Times. 9/15/2007.

445 ANZgene, et al. (2009). "Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20." Nat Genet 41(7):824-8.

446 Pugliatti, M., et al. (2002). “The worldwide prevalence of multiple sclerosis.” Clin Neurol Neurosurg 104:182–191.

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449 Ramagopalan, S. V., et al. (2009). "Expression of the Multiple Sclerosis-Associated MHC Class II
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451 Ramagopalan, S. V., et al. (2008). “Genes for multiple sclerosis.” Lancet 371:283–285.

452 Schmidt, H., et al. (2007). “HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review.” Am J Epidemiol 165(10):1097-1109.

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475 Cardis, E., et al. (2007). "Identification of women with an increased risk of developing radiation-induced breast cancer." Breast Cancer Research 9(3):106.

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480 El Ghissassi, F., et al. (2009). “A review of human carcinogens—Part D: radiation.” Lancet Oncology 10(8):751-2.

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483 Lessov-Schlaggar, C. N., et al. (2008). "Genetics of nicotine dependence and pharmacotherapy." Biochemical Pharmacology 75(1):178-195.

484 Foshee, V., et al. (1992). "Parental and peer characteristics as modifiers of the bond–behavior relationship: An elaboration of control theory." J Health Soc Behav 33(1):66-76.

485 Kardia, S. L. R., et al. (2003). "Association of parental smoking history with nicotine dependence, smoking rate, and psychological cofactors in adult smokers." Addictive Behaviors 28(8):1447-1452.

486 Centers for Disease Control and Prevention. (2006). "Use of Cigarettes and Other Tobacco Products Among Students Aged 13--15 Years --- Worldwide, 1999—2005." MMWR 55(20):553-556.

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495 Tunstall-Pedoe, H., et al. (1999). “Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations: monitoring trends and determinants in cardiovascular disease.” Lancet 353:1547–57.

496 Cabot, R. C. (1904). "The Relation To Alcohol To Arteriosclerosis." J Am Med Assoc XLIII(12):774-775.

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500 Goldberg, D. M., et al. (1995). “Beyond alcohol: Beverage consumption and cardiovascular mortality.” Clin Chim Acta. 237:155–87.

501 da Luz, P. L., et al. (2004). “Wine, alcohol and atherosclerosis: Clinical evidences and mechanisms.” Braz J Med Biol Res. 37: 1275–95.

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508 Frohlich, J. J. (1996). “Effects of alcohol on plasma lipoprotein metabolism.” Clin Chim Acta 246:39–49.

509 da Luz, P. L., et al. (2004). “Wine, alcohol and atherosclerosis: Clinical evidences and mechanisms.” Braz J Med Biol Res 37:1275–95.

510 Bertelli, A., et al. (2002). “Effect of some white wine phenols in preventing inflammatory cytokine release.” Drugs Exp Clin Res 28:11–15.

511 Estruch, R., et al. (2004). “Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: A prospective randomized crossover trial. Effects of wine on inflammatory markers.” Atherosclerosis 175:117–23.

512 Otani, H. (2004). “Reactive oxygen species as mediators of signal transduction in ischemic preconditioning.” Antioxid Redox Signal 6:449–469.

513 Zhuang, H., et al. (2003). “Potential mechanism by which resveratrol, a red wine constituent, protects neurons.” Ann NY Acad Sci 993:276–286.

514 Valdez, L. B., et al. (2004). “Polyphenols and red wine as antioxidants against peroxynitrite and other oxidants.” Biol Res 37:279–86.

515 Arts, I. C. W., et al. (2001). “Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: The Zutphen Elderly Study.” Am J Clin Nutr 74:227–32.

516 Huxley, R. R., et al. (2003). “The relation between dietary flavonol intake and coronary heart disease mortality: A meta-analysis of prospective cohort studies.” Eur J Clin Nutr 57:904–908.

517 El Attar, T. M., et al. (1999). “Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation.” Anticancer Drugs 10:187–193.

518 Caltagirone, S., et al. (2000). “Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.” Int J Cancer 87:595–600.

519 Jang, M., et al. (1997). “Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.” Science 275:218–20.

520 Gronbaek, M., et al. (2000). “Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer.” Ann Intern Med 133:411–419.

521 Klatsky A. L., et al. (1997). “Red wine, white wine, liquor, beer, and the risk for coronary artery disease hospitalization.” Am J Cardiol 80:416–420.

522 Di Castelnuovo, A., et al. (2002). “Meta-analysis of wine and beer consumption in relation to vascular risk.” Circulation 105:2836–2844.

523 Sparwel, J., et al. (2009). "Differential effects of red and white wines on inhibition of the platelet-derived growth factor receptor: impact of the mash fermentation." Cardiovasc Res 81(4): 758-770.

524 Landrault, N., et al. (2003). “Effect of polyphenols-enriched chardonnay white wine in diabetic rats.” J Agric Food Chem 51: 311–318.

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687 Bovet, P., et al. (2006). “Prevalence of cardiovascular risk factors in a middle-income country and estimated cost of a treatment strategy.” BMC Public Health 6: 9.

688 Brown, M. J., et al. (2006). “Hypertension and ethnic group.” BMJ 332: 833–836.

689 Writing Group, M., et al. (2009). "Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee." Circulation 119(3): e21-181.

690 Wolf-Maier K, et al. (2003). “Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States.” JAMA 289:2363–2369.

691 Lifton, R. P., et al. (2001). “Molecular mechanisms of human hypertension.” Cell 104:545–556.

692 Hamilton, M., et al. (1954). “The aetiology of essential hypertension, I: the arterial pressure in the general population.” Clin Sci (Lond). 13: 11–35.

693 Ward, R., et al. (19950. “Familial aggregation and genetic epidemiology of blood pressure. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis, and Management. 2nd ed. New York, NY: Raven Press; pp: 67–88.

694 Shimkets, R. A., et al. (1994). “Liddle’s syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.” Cell 79:407–414.

695 Wilson, F. H., et al. (2001). “Human hypertension caused by mutations in WNK kinases.” Science 293:1107–1112.

696 Sethi, A. A., et al. (2003). "Angiotensinogen Gene Polymorphism, Plasma Angiotensinogen, and Risk of Hypertension and Ischemic Heart Disease: A Meta-Analysis." Arterioscler Thromb Vasc Biol 23(7): 1269-1275.

697 Kato, N., et al. (1999). "Angiotensinogen gene and essential hypertension in the Japanese: extensive association study and meta-analysis on six reported studies." Journal of Hypertension 17(6): 757-763.

698 Gu, C. C., et al. (2005). "Haplotype Association Analysis of AGT Variants with Hypertension-Related Traits: The HyperGEN Study." Human Heredity 60(3): 164-176.

699 Jeunemaitre, X., et al. (1992). “Molecular basis of human hypertension: role of angiotensinogen.” Cell 71: 169–180.

700 Lifton, R. P. (1996). “Molecular genetics of human blood pressure variation.” Science 272: 676–680.

701 Caulfield, M., et al. (1994). “Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med. 330:1629–1633.

702 Jeunemaitre, X., et al. (1997). “Haplotypes of angiotensinogen in essential hypertension.” Am J Hum Genet. 60: 1448–1460.

703 Inoue, I., et al. (1997). “A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.” J Clin Invest. 99: 1786–1797.

704 Yuan, J., et al. (2009). "Angiotensinogen T174M and M235T Variants and Hypertension in the Hani and Yi Minority Groups of China." Biochemical Genetics 47(5): 344-350.

705 Schunkert, H., et al. (1997). “The angiotensinogen T235 variant and the use of antihypertensive drugs in a population-based cohort.” Hypertension. 29: 628–633.

706 Ward, K., et al. (1993). “A molecular variant of angiotensinogen associated with preeclampsia.” Nat Genet 4: 59–61.

707 Gleibermann, L. (1973). “Blood pressure and dietary salt in human populations.” Ecol Food Nutr. 2: 143–156.

708 Nakajima, T., et al. (2004). "Natural Selection and Population History in the Human Angiotensinogen Gene (AGT): 736 Complete AGT Sequences in Chromosomes from Around the World." Am J Hum Genet. 74(5): 898-916.

709 Thompson, E. E., et al. (2004). "CYP3A Variation and the Evolution of Salt-Sensitivity Variants." Am J Hum Genet. 75(6): 1059-1069.

710 Ayala, C., et al. (2009). “Application of Lower Sodium Intake Recommendations to Adults --- United States, 1999—2006.” CDC MMWR 58(11): 281-283.

711 Hunt, S. C., et al. (1998). “Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension: trials of hypertension prevention, phase II.” Hypertension. 32: 393–401.

712 Hunt, S. C., et al. (1999). "Enhanced blood pressure response to mild sodium reduction in subjects with the 235T variant of the angiotensinogen gene." Am J Hypertens 12(5): 460-466.

713 Cook, N. R., et al. (1995). “Implications of small reductions in diastolic blood pressure for primary prevention.” Arch Intern Med. 155:701–709.

714 Svetkey, L. P., et al. (2001). “Angiotensinogen genotype and blood pressure response in the Dietary Approaches to Stop Hypertension (DASH) study.” J Hypertens. 19: 1949–1956.

715 Svetkey, L. P., et al. (1999). “Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial.” Arch Intern Med 159 (3): 285–293.

716 Rutledge, D. R., et al. (1994). "Analysis of two variants of the angiotensinogen gene in essential hypertensive African-Americans." Am J Hypertens 7:651–654.

717 Brunner, E. J., et al. (2007). “Dietary advice for reducing cardiovascular risk.” Cochrane Database Syst Rev. 17(4): CD002128.

718 Cole, J., et al. (2008). "Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population: the stroke prevention in young women study." Thrombosis Journal 6(1):11.

719 Jerrard-Dunne, P., et al. (2004). "Inflammatory Gene Load Is Associated With Enhanced Inflammation and Early Carotid Atherosclerosis in Smokers." Stroke 35(11):2438-2444.

720 Hassan, M., et al. (2008). "Association of beta1-Adrenergic Receptor Genetic Polymorphism With Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Artery Disease." Arch Intern Med 168(7):763-770.

721 Warner, J. H., (1986). “The Therapeutic Perspective: Medical Practice, Knowledge and Identity in America, 1828-1885.” Cambridge: Harvard Univ. Press. pp. 28, 33.

722 Peakman, T., et al. (2001). “Putting the code to work: the promise of pharmacogenetics and pharmacogenomics.” Drug Discov World. 2: 35-40.

723 Ingelman-Sundberg, M. (2001). "Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy." J Intern Med 250(3):186-200.

724 Nishizato, Y., et al. (2003). “Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics.” Clin Pharmacol Ther 73:554-565.

725 König, J., et al. (2006). “Pharmacogenomics of human OATP transporters.” Naunyn Schmiedebergs Arch Pharmacol 372:432-443.

726 Mwinyi, J., et al. (2004). “Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics.” Clin Pharmacol Ther 75:415-421.

727 Georgirene, D. V., et al. (2006). "Genetic risk factors associated with lipid-lowering drug-induced myopathies." Muscle & Nerve 34(2):153-162.

728 Fiegenbaum, M., et al. (2005). “The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment.” Clin Pharmacol Ther 78:551-558.

729 Pasanen, M. K., et al. (2006). “SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid.” Pharmacogenet Genomics 16:873-879.

730 Chasman, D. I., et al. (2004). “Pharmacogenetic study of statin therapy and cholesterol reduction.” JAMA 291:2821–2827.

731 Niemi, M., et al. (2006). “SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin.” Clin Pharmacol Ther 80:356-366.

732 Pasanen, M. K., et al. (2006). "SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid." Pharmacogenetics and Genomics 16(12):873-879.

733 Morimoto, K., et al. (2004). “A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy.” Drug Metab Pharmacokinet 19:453-455.

734 Link, E., et al. (2008). “SLCO1B1 variants and statin-induced myopathy–a genomewide study.” N Engl J Med 359:789–799.

735 Nakamura, Y. (2008). "Pharmacogenomics and Drug Toxicity." N Engl J Med 359(8): 856-858.

736 Simon, T., et al. (2009). "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events." N Engl J Med 360(4):363-375.

737 Giusti, B., et al. (2007). “Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual anti-platelet treatment in high-risk vascular patients.” Pharmacogenet Genomics 17:1057-1064.

738 Mega, J. L., et al. (2009). “Cytochrome P-450 polymorphisms and response to clopidogrel.” N Engl J Med 360:354-362.

739 Wiviott, S. D., et al. (2007). “Prasugrel versus clopidogrel in patients with acute coronary syndromes.” N Engl J Med 357:2001-2015.

740 Frere, C., et al. (2008). “Effect of cytochrome P450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndromes.” Am J Cardiol 101:1088-1093.

741 Yoon, Y. R., et al. (2000). “Relationship of paroxetine disposition to metoprolol metabolic ratio and CYP2D6*10 genotype of Korean subjects.” Clin Pharmacol Ther 67:567–576.

742 Lai, M. L., et al. (1995). “Propranolol disposition in Chinese subjects of different CYP2D6 genotypes.” Clin Pharmacol Ther 58:264–268.

743 DeGeorge, B. R., et al. (2007). “Beta blocker specificity: a building block toward personalized medicine.” J Clin Invest 117(1):86-89.

744 Aithal, G.P., et al. (1999). “Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.” Lancet 353:717–719.

745 Schwarz, U. I., et al. (2008). “Genetic determinants of response to warfarin during initial anticoagulation.” N Engl J Med 358:999–1008.

746 Mega, J. L., et al. (2009). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel." N Engl J Med 360(4):354-362.

747 Shuldiner, A. R., et al. (2009). "Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy." JAMA 302(8):849-857.

748 Simon, T., et al. (2009). "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events." N Engl J Med 360(4):363-375.

749 Collet, J.-P., et al. (2009) "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study." Lancet 373(9660):309-317.

750 Faraday, N., et al. (2007). "Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1." Circulation 115(19): 2490-2496.

751 Cooke, G. E., et al. (1998). "PlA2 polymorphism and efficacy of aspirin." Lancet 351(9111):1253-1253.

752 Undas, A., et al. (2001). "PlA2 Polymorphism of ß3 Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury." Circulation 104(22):2666-2672.

753 Undas, A., et al. (1999). “Platelet glycoprotein IIIa polymorphism, aspirin, and thrombin generation.” Lancet 353:982–983

754 Szczeklik, A., et al. (2000). “Relationship between bleeding time, aspirin, and the PlA1/A2 polymorphism of platelet glycoprotein IIIa.” Br J Haematol 110:965–967.

755 Anderson, J. L., et al. (2007). “Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation.” Circulation 116:2563-2570.

756 Caraco, Y., et al. (2008). “CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study.” Clin Pharmacol Ther 83:460-470.

757 The International Warfarin Pharmacogenetics, C. (2009). "Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data." N Engl J Med 360(8):753-764.

758 U.S. Food and Drug Administration “Critical Path Initiative Warfarin Dosing” www.fda.gov/oc/initiatives/criticalpath/warfarin.html.

Chapter Nine
759 Alzheimer’s Association (2009). “2009 Alzheimer’s Disease Facts and Figures.” Alzheimer’s & Dementia 5(3).

760 Avramopoulos, D. (2009). “Genetics of Alzheimer's disease: recent advances.” Genome Med 1(3):34.

761 Alzheimer, A. (1907). “Ueber eine eigenartige Erkrankung der Himrinde.” Allg Z Psychiat Med 64:146-148.

762 Evans, D. A., et al. (1989). “Prevalence of Alzheimer's disease in a community population of older persons: Higher than previously reported.” JAMA 262(18):2551-2556.

763 Ferri, C. P., et al. (2005). “Global prevalence of dementia: a Delphi consensus study.” Lancet 366(9503):2112–2117.

764 (2009). “World Alzheimer Report 2009.” Alzheimer’s Disease International

765 Schulz, R., et al. (2003). “End-of-life care and the effects of bereavement on family caregivers of persons with dementia.” New England Journal of Medicine 349(20):1936–1942.

766 Evridiki, P., et al. (2007). "Caring for a relative with dementia: family caregiver burden." Journal of Advanced Nursing 58(5):446-457.

767 Gatz, M., et al. (2006). "Role of Genes and Environments for Explaining Alzheimer Disease." Arch Gen Psychiatry 63(2):168-174.

768 Zhang, S. H., et al. (1992). “Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.” Science 258:468–471.

769 Jiang, Q., et al. (2008). "ApoE Promotes the Proteolytic Degradation of A[beta]." Neuron 58(5): 681-693.

770 Namba, Y., et al. (1991). “Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease.” Brain Res 541:163–166.

771 Arendt, T., et al. (1997). “Plastic neuronal remodeling is impaired in patients with Alzheimer's disease carrying apolipoprotein epsilon 4 allele.” J Neurosci 17:516–529.

772 Beffert, U., et al. (1998). “The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer's disease.” Br Res Rev 27:119–142.

773 Wang, C., et al. (2005). "Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology." Neurobiology of Disease 18(2):390-398.

774 Utermann, G., et al. (1980). “Genetics of the apolipoprotein E system in man.” Am J Hum Genet 32:339-347.

775 Poirier, J. (2005). “Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer's disease.” Neurobiology of Aging 26(3):355-361.

776 Bertrand, P., et al. (1995). "Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease." Molecular Brain Research 33(1):174-178.

777 Beffert, U., et al. (1999). "Apolipoprotein E and beta-amyloid levels in the hippocampus and frontal cortex of Alzheimer's disease subjects are disease-related and apolipoprotein E genotype dependent." Brain Research 843(1-2):87-94.

778 Corder, E. H., et al. (1993). “Gene dose of apolipoprotein E type 4 allele and the risk of AD in late onset families.” Science 261:921-923.

779 Rubinsztein, D. C., et al. (1999). "Apolipoprotein E Genetic Variation and Alzheimer's Disease." Dement Geriatr Cogn Disord 10(3):199-209.

780 Myers, R. H., et al. (1996). “Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study.” Neurology 46(3):673-677.

781 Nalbantoglu, J., et al. (1994). “Predictive value of apolipoprotein E genotyping in Alzheimer's disease.” Ann Neurol 36:889-895.

782 Roses, A. D., et al. (1995). “Measuring the genetic contribution of APOE in late onset Alzheimer disease.” Am J Hum Genet 57:A202.

783 Farrer, L. A., et al. (1997). "Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis." JAMA 278(16):1349-1356.

784 Tang, M.-X., et al. (1998). "The APOE-{epsilon}4 Allele and the Risk of Alzheimer Disease Among African Americans, Whites, and Hispanics." JAMA 279(10):751-755.

785 Jacob, R., et al. (2004). "ApoE genotype accounts for the vast majority of AD risk and AD pathology." Neurobiol Aging 25(5):641-650.

786 Takei, N., et al. (2009). "Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese." Genomics 93(5):441-448.

787 Jacob, R., et al. (2004). "ApoE genotype accounts for the vast majority of AD risk and AD pathology." Neurobiology of aging 25(5):641-650.

788 Ashford, J. W., et al. (2002). "Non-familial Alzheimer's disease is mainly due to genetic factors." J Alzheimers Dis 4(3):169-77.

789 Gatz, M., et al. (2006). “Role of genes and environments for explaining Alzheimer disease.” Arch Gen Psychiatry 63:168–174.

790 Caselli, R. J., et al. (2009). "Longitudinal Modeling of Age-Related Memory Decline and the APOE epsilon4 Effect." N Engl J Med 361(3):255-263.

791 Caselli, R. J., et al. (2007). “Cognitive domain decline in healthy apolipoprotein E 4 homozygotes before the diagnosis of mild cognitive impairment.” Arch Neurol 64:1306-1311.

792 Caselli, R. J., et al. (2004). “Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.” Neurology 62:1990-1995.

793 Baxter, L. C., et al. (2003). “Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease.” Neurobiol Aging 24:947-952.

794 Martins, C. A. R., et al. (2005). "APOE alleles predict the rate of cognitive decline in Alzheimer disease: A nonlinear model." Neurology 65(12): 1888-1893.

795 Saunders, A. M., et al. (1993). "Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease." Neurology 43(8): 1467-72.

796 Lambert, J.-C., et al. (2009). "Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease." Nat Genet doi:10.1038/ng.439.

797 Harold, D., et al. (2009). "Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease." Nat Genet doi:10.1038/ng.440.

798 Rogaeva, E., et al. (2007). “The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.” Nat Genet 2:168–177.

799 Li, Y., et al. (2008). “SORL1 variants and risk of late-onset Alzheimer's disease.” Neurobiol Dis 29:293–296.

800 Meng, Y., et al. (2007). "Association between SORL1 and Alzheimer's disease in a genome-wide study." NeuroReport 18(17):1761-1764.

801 Lee, J. H., et al. (2007). “The association between genetic variants in SORL1 and Alzheimer disease in an urban, multiethnic, community-based cohort.” Arch Neurol 64:501-506.

802 Bettens, K., et al. (2008). “SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population.” Hum Mutat 29:769-770.

803 Beecham, G. W., et al. (2009). “Genome-wide Association Study Implicates a Chromosome 12 Risk Locus for Late-Onset Alzheimer Disease.” Am J Hum Genet 84(1):35-43.

804 Cuenco, T., et al. (2008). "Association of Distinct Variants in SORL1 With Cerebrovascular and Neurodegenerative Changes Related to Alzheimer Disease." Arch Neurol 65(12):1640-1648.

805 Kimura, R., et al. (2009). "SORL1 is genetically associated with Alzheimer disease in a Japanese population." Neuroscience Letters 461(2):177-180.

806 Tan, E. K., et al. (2009). "SORL1 haplotypes modulate risk of Alzheimer's disease in Chinese." Neurobiology of Aging 30(7):1048-1051.

807 Reiman, E. M., et al. (2007). “GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.” Neuron 54:713-720.

808 Sleegers, K., et al. (2009). “Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementia.” Hum Mutat 30:E338-344.

809 Ikram, M. A.,et al. (2009). "The GAB2 Gene and the Risk of Alzheimer's Disease: Replication and Meta-Analysis." Biological Psychiatry 65(11): 995-999.

810 Bertram, L., et al. (2008). “Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.” Am J Hum Genet 83:623-632

811 Roses, A. D., et al. (2009). “Apoe-3 And Tomm-40 Haplotypes Determine Inheritance Of Alzheimer's Disease Independently Of Apoe-4 Risk.” Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease. Vienna Austria. Presentation O1-06-01 on Jul 12, 2009 from 3-5PM.

812 Potkin, S. G., et al. (2009). "Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease." PLoS ONE 4(8):e6501.

813 Devi, L., et al. (2006). "Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer's Disease Brain Is Associated with Mitochondrial Dysfunction." J. Neurosci. 26(35): 9057-9068.

814 Bertram, L., et al. (2007). “Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.” Nat Genet 39:17-23.

815 Wellington, C. L. (2004). "Cholesterol at the crossroads: Alzheimer's disease and lipid metabolism." Clinical Genetics 66(1): 1-16.

816 Waring, S. C., et al. (2008). "Genome-Wide Association Studies in Alzheimer Disease." Arch Neurol 65(3): 329-334.

817 Caselli, R. J., et al. (2008). “Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment.” Arch Neurol 65:1231-1236.

818 Bennett, D. A., et al. (2005). "Education modifies the association of amyloid but not tangles with cognitive function." Neurology 65(6): 953-955.

819 Sigrid Botne, S., et al. (2008). "Risk-reducing effect of education in Alzheimer's disease." Int J Geriatr Psychiatry. 23(11): 1156-1162.

820 Stern, Y., et al. (1999). "Rate of memory decline in AD is related to education and occupation: Cognitive reserve?" Neurology 53(9): 1942-.

821 Roe, C. M., et al. (2007). "Education and Alzheimer disease without dementia: Support for the cognitive reserve hypothesis." Neurology 68(3): 223-228.

822 Ngandu, T., et al. (2007). "Education and dementia: What lies behind the association?" Neurology 69(14): 1442-1450.

823 Elias, M. F., et al. (1997). “Role of age, education, and gender on cognitive performance in the Framingham Heart Study: community-based norms.” Exp Aging Res 23:201-235.

824 Launer, L. J., et al. (1999). “Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses.” Neurology 52:78-84.

825 Ott, A., et al. (1999). “Education and the incidence of dementia in a large population-based study: the Rotterdam Study.” Neurology 52:663-666.

826 Ganguli, M., et al. (2000). “Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project.” Neurology 54:1109-1116

827 Kukull, W. A., et al. (2002). "Dementia and Alzheimer Disease Incidence: A Prospective Cohort Study." Arch Neurol 59(11): 1737-1746.

828 Perneczky, R., et al. (2009). "Education Attenuates the Effect of Medial Temporal Lobe Atrophy on Cognitive Function in Alzheimer's Disease: The MIRAGE Study." J Alzheimers Dis. DOI: 10.3233/JAD-2009-1117.

829 Snowdon, D. A., et al. (1996). “Linguistic ability in early life and cognitive function and Alzheimer's disease in late life: findings from the Nun Study.” JAMA 275: 528–532.

830 Snowdon, D. A., et al. (2000). "Linguistic Ability in Early Life and the Neuropathology of Alzheimer's Disease and Cerebrovascular Disease: Findings from the Nun Study." Ann N Y Acad Sci 903:34-8.

831 Iacono, D.,et al. (2009). "The Nun Study. Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life." Neurology: WNL.0b013e3181b01077.

832 Ball, K., et al. (2002). “Effect of cognitive training interventions with older adults: a randomised control trial.” JAMA 288:2271–2281.

833 Willis, S. L.,et al. (2006). "Long-term Effects of Cognitive Training on Everyday Functional Outcomes in Older Adults." JAMA 296(23): 2805-2814.

834 Valenzuela, M. J., et al. (2008). “Brain reserve and the prevention of dementia.” Curr Opin Psychiatry 21: 296–302.

835 Valenzuela, M. J. (2008). “Brain reserve and the prevention of dementia.” Curr Opin Psychiatry 21(3):296-302.

836 May, A., et al. (2007). “Structural brain alterations following 5 days of intervention: dynamic aspects of neuroplasticity.” Cerebral Cortex 17:205–210.

837 Olesen, P., et al. (2005). “Increased prefrontal and parietal activity after training of working memory.” Nat Neurosci 7:75–79.

838 Fratiglioni, L., et al. (2004). “An active and socially integrated lifestyle in late life might protect against dementia.” Lancet Neurol 3: 343–53.

839 Mahncke, H., et al. (2006). “Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomised, controlled study.” Proc Natl Acad Sci U S A 103:12523–12528.

840 Basak, C., et al. (2008). "Can training in a real-time strategy video game attenuate cognitive decline in older adults?" Psychology and Aging 23(4): 765-777.

841 Hamilton, A. “Can Gaming Slow Mental Decline in the Elderly?” Time 7/11/2009.

842 Friedman, G., et al. (1999). “Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury.” Neurology 52: 244–248.

843 Lichtman, S. W., et al. (2000). “Apolipoprotein E and functional recovery from brain injury following post-acute rehabilitation.” Neurology 55: 1536–1539.

844 Laskowitz, D. T., et al. (2007). "COG1410, a Novel Apolipoprotein E-based Peptide, Improves Functional Recovery in a Murine Model of Traumatic Brain Injury." Journal of Neurotrauma 24(7): 1093.

845 Wang, H., et al. (2007). "An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: Evidence of pharmacogenomic interaction." Neuroscience 144(4): 1324-1333.

846 Grodstein, F. (2007). “Cardiovascular risk factors and cognitive function.” Alzheimer Dement 3:S16–S22.

847 Beydoun, M. A., et al. (2008). “Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis.” Obes Rev 9:204–218.

848 Gorospe, E. C., et al. (2007). “The risk of dementia with increased body mass index.” Age Ageing 36:23–29.

849 Hassing, L. B.,et al. (2009). "Overweight in midlife and risk of dementia: a 40-year follow-up study." Int J Obes DOI: 10.1038/ijo.2009.104.

850 Miia, K., et al. (2008). "Apolipoprotein E-4 magnifies lifestyle risks for dementia: a population-based study." Journal of Cellular and Molecular Medicine 12(6b): 2762-2771.

851 Tyas, S. L., et al. (2003). "Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study." Neurobiology of Aging 24(4): 589-596.

852 Juan, D., et al. (2004). “A 2-year follow-up study of cigarette smoking and risk of dementia.” Eur J Neurol 11:277–282.

853 Kivipelto, M., et al. (2001). “Midlife vascular risk factors and Alzheimer’s disease in later life.” BMJ 322:1447-1451.

854 Notkola, I-L., et al. (1998). “Serum total cholesterol, apolipoprotein E epsilon4 allele, and Alzheimer's disease.” Neuroepidemiology 17:14-20.

855 Erickson, K. I., et al. (2009). “Aerobic exercise effects on cognitive and neural plasticity in older adults.” Br J Sports Med 43(1):22-4.

856 Yu, F., et al. (2006). “Improving cognition and function through exercise intervention in Alzheimer's disease.” J Nurs Scholarsh 38(4):358-65.

857 Dishman, R. K., et al. (2006). “Neurobiology of exercise.” Obesity (Silver Spring) 14(3):345-56.

858 Kramer, A. F., et al. (2007). “Capitalizing on cortical plasticity: influence of physical activity on cognition and brain function.” Trends Cogn Sci 11: 342–48.

859 Nichol, K. E., et al. (2008). “Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid.” J Neuroinflammation 5:13.

860 Adlard, P. A., et al. (2005). “Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease.” J Neurosci 25(17):4217-21.

861 Friedland, R. P., et al. (2001). “Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members.” Proc Natl Acad Sci U S A 98(6):3440-5.

862 Deeny, S. P., et al. (2008). “Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers.” Biol Psychol 78: 179–87.

863 Schuit, A. J., et al. (2001). “Physical activity and cognitive decline, the role of the apolipoprotein e4 allele.” Med Sci Sports Exerc 33(5):772-7.

864 Cotman, C. W., et al. (2002). “Exercise: a behavioral intervention to enhance brain health and plasticity.” Trends Neurosci 25(6):295-301.

865 Lautenschlager, N. T., et al. (2008). “Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.” Jama 300(9):1027-37.

866 Lucia, A., et al. (2009). "Exercise is beneficial for patients with Alzheimer's disease: A call to action." Br J Sports Med: bjsm.2009.061200.

867 van Uffelen, J. G., et al. (2008). “Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial.” Br J Sports Med 42(5):344-51.

868 Suvi, R., et al. (2007). "Work-related physical activity and the risk of dementia and Alzheimer's disease." Int J Geriatr Psychiatry 22(9): 874-882.

869 Rovio, S., et al. (2005). “Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease.” Lancet Neurol 4:705-711.

870 Lindsay, J., et al. (2002). "Risk Factors for Alzheimer's Disease: A Prospective Analysis from the Canadian Study of Health and Aging." Am. J. Epidemiol. 156(5): 445-453.

871 Scarmeas, N., et al. (2009). "Mediterranean Diet and Mild Cognitive Impairment." Arch Neurol 66(2): 216-225.

872 Solfrizzi, V., et al. (2006). "Dietary intake of unsaturated fatty acids and age-related cognitive decline: A 8.5-year follow-up of the Italian Longitudinal Study on Aging." Neurobiology of Aging 27(11): 1694-1704.

873 Panza, F., et al. (2004). "Mediterranean diet and cognitive decline." Public Health Nutrition 7(07): 959-963.

874 Sofi, F., et al. (2008). "Adherence to Mediterranean diet and health status: meta-analysis." BMJ 337(sep11_2): a1344-.

875 Serra-Majem, L., et al. (2006). "Scientific Evidence of Interventions Using the Mediterranean Diet: A Systematic Review." Nutrition Reviews 64:27-47.

876 Scarmeas, N., et al. (2006). “Mediterranean diet and risk for Alzheimer's disease.” Ann Neurol 59(6):912-921.

877 Scarmeas, N., et al. (2006). “Mediterranean diet, Alzheimer disease, and vascular mediation.” Arch Neurol 63(12):1709-1717.

878 Willett, W. C., et al. (1995). "Mediterranean diet pyramid: a cultural model for healthy eating." Am J Clin Nutr 61(6): 1402S-1406.

879 Panza, F., et al. (2006). “Lipid metabolism in cognitive decline and dementia.” Brain Res Rev 51:275–292.

880 Ribeiro, J. A., et al. (2002). "Adenosine receptors in the nervous system: pathophysiological implications." Progress in Neurobiology 68(6): 377-392.

881 Oscar, P. D. l., et al. (2003). "Neuroprotection by caffeine and adenosine A2a receptor blockade of β2-amyloid neurotoxicity." British Journal of Pharmacology 138(7): 1207-1209.

882 Dall'Igna, O. P., et al. (2007). "Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25-35)-induced cognitive deficits in mice." Experimental Neurology 203(1): 241-245.

883 Svilaas, A., et al. (2004). "Intakes of Antioxidants in Coffee, Wine, and Vegetables Are Correlated with Plasma Carotenoids in Humans." J. Nutr. 134(3): 562-567.

884 Vingtdeux, V., et al. (2008). "Therapeutic potential of resveratrol in Alzheimer's disease." BMC Neuroscience 9(Suppl 2): S6.

885 Karuppagounder, S. S., et al. (2009). "Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease." Neurochemistry International 54(2): 111-118.

886 Marambaud, P., et al. (2005). "Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid- β Peptides." J. Biol. Chem. 280(45): 37377-37382.

887 Kim, D., et al. (2007). “SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.” EMBO J. 26(13): 3169–3179.

888 Rosso, A., et al. (2008). "Caffeine: Neuroprotective Functions in Cognition and Alzheimer’s Disease." American journal of Alzheimer's disease and other dementias. Am J Alzheimers Dis Other Demen 23(5):417-22

889 Rees, K.,et al. (1999). "The influences of age and caffeine on psychomotor and cognitive function." Psychopharmacology 145(2): 181-188.

890 Johnson-Kozlow, M., et al. (2002). "Coffee Consumption and Cognitive Function among Older Adults." Am. J. Epidemiol. 156(9): 842-850.

891 Eskelinen, M. H., et al. (2009). "Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE Study." Journal of Alzheimer's Disease 16(1): 85-91.

892 Lindsay, J., et al. (2002). "Risk Factors for Alzheimer's Disease: A Prospective Analysis from the Canadian Study of Health and Aging." Am. J. Epidemiol. 156(5): 445-453.

893 Maia, L., et al. (2002). "Does caffeine intake protect from Alzheimer's disease?" European Journal of Neurology 9(4): 377-382.

894 Luchsinger, J. A., et al. (2004). “Alcohol intake and risk of dementia.” J Am Geriatr Soc 52:540–546.

895 Orgogozo, J. M., et al. (1997). "Consommation de vin et démence chez les sujets âgés : étude épidémiologique prospective de terrain dans la région de Bordeaux." Rev Neurol 153(3):185-92.

896 Ruitenberg, A., et al. (2002). "Alcohol consumption and risk of dementia: the Rotterdam Study." Lancet 359(9303): 281-286.

897 Dufouil, C., et al. (2000). “Influence of apolipoprotein E genotype on the risk of cognitive deterioration in moderate drinkers and smokers.” Epidemiology 11: 280–284.

898 Linday, J., et al. (2002). “Risk Factors for Alzheimer's disease. A prospective analysis from the Canadian Study of Health and Aging.” Am J Epidemiol 156: 445–453.

899 Weggen, S., et al. (2001). “A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity.” Nature 414:212–216.

900 Lim, G. P., et al. (2000). “Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease.” J Neurosci 20(15):5709–5714.

901 Yan, Q., et al. (2003). “Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease.” J Neurosci 23:7504–7509.

902 Breteler, M. M., et al. (1991). "Medical history and the risk of Alzheimer's disease: a collaborative re- analysis of case-control studies. EURODEM Risk Factors Research Group." Int. J. Epidemiol. 20(suppl_2): S36-42.

903 Li, G., et al. (1992). “A case-control study of Alzheimer's disease in China.” Neurology. 42(8):1481-8.

904 McGeer, P. L., et al. (1990). “Anti-inflammatory drugs and Alzheimer disease.” Lancet 335:1037.

905 McGeer, P. L., et al. (1996). “Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies.” Neurology 47:425–432.

906 in’t Veld, B. A., et al. (2001). “Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.” New Engl J Med 345: 1515–1521.

907 Stewart, W. F., et al. (1997). “Risk of Alzheimer's disease and duration of NSAID use.” Neurology 48(3): 626–632.

908 Zandi, P. P., et al. (2002). “Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County study.” Neurology 59(6):880–886.

909 McGeer, P. L., et al. (2007). "NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies." Neurobiology of Aging 28(5): 639-647.

910 Rogers, J., et al. (1993). “Clinical trial of indomethacin in Alzheimer's disease.” Neurology 43:1609–11.

911 (1994). “The Canadian Study of Health and Aging: risk factors for Alzheimer's disease in Canada.” Neurology 44(11):2073–2080.

912 Landi, F., et al. (2003). “Non-steroidal anti-inflammatory drug (NSAID) use and Alzheimer disease in community-dwelling elderly patients.” Am J Geriatr Psychiat 11:179–185.

913 Yip, A. G., et al. (2005). “Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE study.” BMC Geriatr 5:2.

914 Szekely, C. A., et al. (2008). "NSAID use and dementia risk in the Cardiovascular Health Study*: Role of APOE and NSAID type." Neurology 70(1): 17-24.

915 Pasqualetti, P., et al. (2009). “A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease.” Aging Clin Exp Res 21(2):102-10.

916 Ophir, G., et al. (2005). “Apolipoprotein E4 enhances brain inflammation by modulation of the NF-kappaB signaling cascade.” Neurobiol Dis 20:709–718.

917 Ophir, G., et al. (2003). “Human apoE3 but not apoE4 rescues impaired astrocyte activation in apoE null mice.” Neurobiol Dis 12:56–64.

918 Casolini, P., et al. (2002). “Inhibition of COX-2 reduces the age-dependent increase of hippocampal inflammatory markers, corticosterone secretion, and behavioral impairments in the rat.” J Neurosci Res 68: 337–43.

919 Thomas, T., et al. (2001). “Aspirin and nonsteroidal anti-inflammatory drugs inhibit amyloid-beta aggregation.” Neuroreport 12: 3263–67.

920 Hayden, K. M., et al. (2007). “Does NSAID use modify cognitive trajectories in the elderly? The Cache County study.” Neurology 69: 275–82.

921 Fowkes, G. “No evidence for the routine use of aspirin in people with asymptomatic vascular events: results from the AAA study.” European Society of Cardiology Congress 2009, Barcelona, Spain, 8/30/09.

922 Jick, H., et al. (2000). “Statins and the risk of dementia.” Lancet 356: 1627–1631.

923 Wolozin, B., (2000). “Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors.” Arch Neurol 57: 1439–1443.

924 Rockwood, K., et al. (2002). “Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people.” Arch Neurol 59: 223–227.

925 Hajjar, I., et al. (2002). "The Impact of the Use of Statins on the Prevalence of Dementia and the Progression of Cognitive Impairment." J Gerontol A Biol Sci Med Sci 57(7): M414-418.

926 Fassbender, K., et al. (2001). “Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo.” Proc Natl Acad Sci USA 98:5856–5861.

927 Simons, M., et al. (1998). “Cholesterol depletion inhibits the generation of -amyloid in hippocampal neurons.” Proc Natl Acad Sci U S A 95:6460-6464.

928 Parvathy, S., et al. (2004). "Atorvastatin-induced activation of Alzheimer's alpha secretase is resistant to standard inhibitors of protein phosphorylation-regulated ectodomain shedding." J Neurochem 90(4): 1005-1010.

929 Li, G., et al. (2007). "Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease." Neurology 69(9): 878-885.

930 Noble, W., et al. (2003). “Cdk5 is a key factor in tau aggregation and tangle formation in vivo.” Neuron 38:555–565.

931 Lee, M. S., et al. (2000). “Neurotoxicity induces cleavage of p35 to p25 by calpain.” Nature 405:360–364.

932 Li, Y., et al. (2003). “Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway.” J Neurosci 23:1605–1611.

933 Serajuddin, A. T., et al. (1991). “Relative lipophilicities, solubilities, and structure-pharmacological considerations of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors pravastatin, lovastatin, mevastatin, and simvastatin.” J Pharm Sci 80(9):830-4.

934 Vuletic, S., et al. (2006). "Statins of Different Brain Penetrability Differentially Affect CSF PLTP Activity." Dement Geriatr Cogn Disord 22(5-6): 392-398.

935 Botti, R. E., et al. (1991). “Concentrations of pravastatin and lovastatin in cerebrospinal fluid in healthy subjects.” Clin Neuropharmacol 14: 256-261.

936 Saheki, A., et al. (1994). “In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors.” Pharm Res 11: 305-311.

937 Riekse, R. G., et al. (2006). “Effect of statins on Alzheimer’s disease biomarkers in cerebrospinal fluid.” J Alzheimer Dis 10:399–406.

938 Arvanitakis, Z., et al. (2008). "Statins, incident Alzheimer disease, change in cognitive function, and neuropathology." Neurology 70(19_Part_2): 1795-1802 and article correspondences.

939 Rea, T. D., et al. (2005). "Statin Use and the Risk of Incident Dementia: The Cardiovascular Health Study." Arch Neurol 62(7): 1047-1051.

940 Li, G., et al. (2006). “Differential effect of statins on risk of AD by age, sex and APOE genotype: findings from a community-based prospective cohort study.” Alzheimer Dis 20:S103–S104.

941 Dufouil, C., et al. (2005). "APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: The Three-City Study." Neurology 64(9): 1531-1538.

942 Balluz, L. S., et al. (2000). “Vitamin and mineral supplement use in the United States. Results from the third National Health and Nutrition Examination Survey.” Arch Fam Med 9:258-62.

943 Eidelman, R. S., et al. (2004). “Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease.” Arch Intern Med 164:1552-6.

944 Shekelle, P. G., et al. (2004). “Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease.” J Gen Intern Med 19:380-9.

945 Vivekananthan, D. P., et al. (2003). “Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials.” Lancet 361:2017-23.

946 Miller, E. R., et al. (2005). “Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.” Ann Int Med 142:37–46.

947 Institute of Medicine. (2000). “Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids.” A report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food Nutrition Board. Washington, DC: National Academies Pr.

948 Issac, M. G., et al. (2008). “Vitamin E for Alzheimer's disease and mild cognitive impairment.” Cochrane Database Syst Rev. (3):CD002854.

949 The HOPE and HOPE-TOO Trial Investigators. (2005). "Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled Trial." JAMA 293(11): 1338-1347.

950 Huang, H. Y., et al. (2003). “Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans.” J Nutr 133:3137-40.

951 van Haaften, R. I., et al. (2003). “Inhibition of various glutathione S-transferase isoenzymes by RRR-alpha-tocopherol.” Toxicol In Vitro 17:245-51.

952 Mozaffarian, D., et al. (2006). "Fish intake, contaminants, and human health: evaluating the risks and the benefits." JAMA 296(15):1885–1899.

953 Wang, C., et al. (2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition 84(1):5–17.

954 Mozaffarian, D., et al. (2005). “Fish consumption and stroke risk in elderly individuals: the cardiovascular health study.” Arch Intern Med 165:200–206.

955 Mozaffarian D., et al. (2006). “Fish intake, contaminants, and human health: evaluating the risks and the benefits.” JAMA 296:1885–1899.

956 Mozaffarian, D., et al. (2003). “Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study.” Circulation 107:1372–1377.

957 Lee, J. H., et al. (2008). "Omega-3 Fatty Acids for Cardioprotection." Mayo Clinic Proceedings 83(3): 324-332.

958 Harris, W. S., et al. (2004). “Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives.” Atherosclerosis 197:12–24.

959 “FDA Announces Qualified Health Claims for Omega-3 Fatty Acids.” FDA News Release. 9/8/2004.

960 Youdim, K. A., et al. (2000). “Essential fatty acids and the brain: possible health implications.” Int J Dev Neurosci 18:383–99.

961 Freemantle, E., et al. (2006). “Omega-3 fatty acids, energy substrates, and brain function during aging.” Prostaglandins Leukot Essent Fatty Acids 75:213–20.

962 Schaefer, E. J., et al. (2006). “Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study.” Arch Neurol 63:1545–50.

963 Samieri, C., et al. (2008). “Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk.” Am J Clin Nutr 88:714–21.

964 Heude, B., et al. (2003). “Cognitive decline and fatty acid composition of erythrocyte membranes—the EVA Study.” Am J Clin Nutr 77:803–8.

965 Ma, Q. L., et al. (2007). “Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.” J Neurosci 27:14299–14307.

966 Bazan, N. G. (2005). “Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress.” Brain Pathol 15:159–166.

967 Tassoni, D., et al. (2008). “The role of eicosanoids in the brain.” Asia Pac J Clin Nutr 17:(Suppl. 1) 220–228.

968 Wu, A. (2004). “Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.” J Neurotrauma 21:1457–1467.

969 Innis, S. M., et al. (2007). “Dietary (n-3) fatty acids and brain development.” J Nutr 137:855–859.

970 Green, K. N., et al. (2007). “Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels.” J Neurosci 27:4385–4395.

971 Lukiw, W. J., et al. (2005). “A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease.” J Clin Invest 115:2774–2783.

972 Morris, M. C., et al. (2003). “Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.” Arch Neurol 60:940–946.

973 Huang, T. L.,et al. (2005). "Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4." Neurology 65(9): 1409-1414.

974 Minihane, A. M., et al. (2000). "ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype." Arterioscler Thromb Vasc Biol 20(8): 1990-1997.

975 Whalley, L. J., et al. (2008). “n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood.” Am J Clin Nutr 87:449–454.

976 Jofre-Monseny, L., et al. (2008). “Impact of apoE genotype on oxidative stress, inflammation and disease risk.” Mol Nutr Food Res 52:131–145.

977 Quinn, J. F., et al. (2009). "A clinical trial of docosahexanoic acid (DHA) for the treatment of Alzheimer's disease." Alzheimer’s & Dementia 5(4): P84.

978 Bonnie, J. H. (2007). "New Studies Support the Therapeutic Value of Meditation." Explore (New York, N.Y.) 3(5): 449-452.

979 Srinivasan, N., et al. (2007). “Concentrative meditation enhances preattentive processing: a mismatch negativity study.” Neuroreport 18(16):1709-12

980 Streeter, C. C., et al. (2007). "Yoga Asana Sessions Increase Brain GABA Levels: A Pilot Study." J Altern Complement Med 13(4): 419.

981 Luders, E., et al. (2009). "The underlying anatomical correlates of long-term meditation: Larger hippocampal and frontal volumes of gray matter." NeuroImage 45(3): 672-678.

982 Giuseppe, P., et al. (2007). "Age effects on gray matter volume and attentional performance in Zen meditation." Neurobiology of Aging 28(10): 1623-1627.

983 Lee, B. K., et al. (2008). “Apolipoprotein E genotype, cortisol, and cognitive function in community-dwelling older adults.” Am J Psychiatry 165:1456–1464.

984 Peavy, G. M., et al. (2007). “The effects of prolonged stress and APOE genotype on memory and cortisol in older adults.” Biol Psychiatry 62:472–478.

985 Drzezga, A., et al. (2005). “Cerebral glucose metabolism in patients with AD and different APOE genotypes.” Neurology 64: 102–7.

986 Mosconi, L., et al. (2004). “Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease.” J Neurol Neurosurg Psychiatry 75: 370–76.

987 Small, G. W., et al. (2006). “PET of brain amyloid and tau in mild cognitive impairment.” N Engl J Med 355: 2652–63.

988 Pike, K. E., et al. (2007). “ß -amyloid imaging and memory in nondemented individuals: evidence for preclinical Alzheimer's disease.” Brain 130(11): 2837–44.

989 Kemppainen, N. M., et al. (2007). “PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment.” Neurology 68: 1603–6.

990 Giacobini, E. (2006). “Cholinesterases in human brain: the effect of cholinesterase inhibitors on Alzheimer’s disease and related disorders.” In: The Brain Cholinergic System in Health and Disease Oxon: Informa Healthcare, pg. 235–264.

991 Cacabelos, R. (2007). “Molecular pathology and pharmacogenomics in Alzheimer’s disease: polygenic-related effects of multifactorial treatments on cognition, anxiety and depression.” Methods Find Exp Clin Pharmacol 29(Suppl A):1–91.

992 Cacabelos, R. (2007). “Donepezil in Alzheimer’s disease: From conventional trials to Pharmacogenetics.” Neuropsychiatr Dis Treat 3(3):303-33.

Chapter TEN
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994 Boyle, P., et al. (2008), “World Cancer Report 2008.” IARC. Lyon: International Agency for Research on Cancer. p 9.

995 (2008). “The Global Burden of Disease, 2004 Update.” World Health Organization.

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998 Cho, M. K., et al. (1999). “Commercialization of BRCA1/2 Testing: Practitioner Awareness and Use of a New Genetic Test.” Am J Med Genet 83(3):157–163.

999 Domchek, S. M., et al. (2006). "Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study." Lancet Oncol 7(3): 223-229.

1000 Rebbeck, T. R., et al. (2002). "Prophylactic Oophorectomy in Carriers of BRCA1 or BRCA2 Mutations." N Engl J Med 346(21): 1616-1622.

1001 Hartmann, L. C., et al. (2001). "Efficacy of Bilateral Prophylactic Mastectomy in BRCA1 and BRCA2 Gene Mutation Carriers." J. Natl. Cancer Inst. 93(21): 1633-1637.

1002 “Skin Cancer Facts.” American Cancer Society. Last Revised: 7-6-2009.

1003 Thompson, J. F.,et al. (2005). “Cutaneous melanoma.” Lancet 365:687-701.

1004 “Skin Cancer Facts.” American Cancer Society. Last Revised: 7-6-2009.

1005 Gruber, S. B., et al. (1993). “Sensitivity and specificity of self-examination for cutaneous malignant melanoma risk factors.” Am J Prev Med 9(1):50-54.

1006 Aspinwall, L. G., et al. (2008). "CDKN2A/p16 Genetic Test Reporting Improves Early Detection Intentions and Practices in High-Risk Melanoma Families." Cancer Epidemiol Biomarkers Prev 17(6):1510-1519.

1007 Lisa, G. A., et al. (2009). "Patterns of photoprotection following CDKN2A/p16 genetic test reporting and counseling." Journal of the American Academy of Dermatology 60(5):745-757.

1008 Heffernan, T. P., et al. (2009). "ATR-Chk1 Pathway Inhibition Promotes Apoptosis after UV Treatment in Primary Human Keratinocytes: Potential Basis for the UV Protective Effects of Caffeine." J Invest Dermatol 129(7): 1805-1815.

1009 Hakim, I. A., et al. (2000). “Tea intake and squamous cell carcinoma of the skin: influence of type of tea beverages.” Cancer Epidemiol Biomarkers Prev 9:727–731.

1010 Wang, Z. Y., et al. (1992). “Inhibitory effect of green tea in drinking water in tumorigenesis by ultraviolet light and 12-O-tetradecanoylphorbol-13-acetate in the skin of SKH-1 mice.” Cancer Res 52:1162- 71.

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1014 Abel, E., et al. (2007). “Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women.” Eur J Cancer Prev 16:446–452.

1015 Kerzendorfer, C., et al. (2009). "UVB and Caffeine: Inhibiting the DNA Damage Response to Protect Against the Adverse Effects of UVB." J Invest Dermatol 129(7): 1611-1613.

1016 Raimondi, S., et al. (2008). “MC1R variants, melanoma and red hair color phenotype: a meta-analysis.” Int J Cancer 122(12):2753–2760.

1017 Rouzaud, F.,et al. (2005). “MC1R and the response of melanocytes to ultraviolet radiation.” Mutat Res 571:133-52.

1018 Kollias, N., et al. (1991). “Photoprotection by melanin.” J Photochem Photobiol B 9:135-160.

1019 Ranadive, N. S.,et al. (1986). “Role of reactive oxygen species and free radicals from melanins in photoinduced cutaneous inflammations.” Pathol Immunopathol Res 5:118-39.

1020 Gerstenblith, M. R., et al. (2007). “Comprehensive evaluation of allele frequency differences of MC1R variants across populations.” Hum Mutat 28:495-505.

1021 Kennedy, C.,et al. (2001). “Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.” J Invest Dermatol 117:294-300.

1022 Landi, M. T., et al. (2005). “MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population.” J Natl Cancer Inst 97:998-1007.

1023 Liem, E. B., et al. (2004). “Anesthetic requirement is increased in redheads.” Anesthesiology 101(2):279–283.

1024 Liem, E. B., et al. (2005). “Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads.” Anesthesiology 102(3):509–514.

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