The application proposed to continue and extend the analysis of blood samples that were collected at baseline as part of the Physicians' Health Study (PHS), a randomized trial of aspirin and beta-carotene among 22,071 U.S. male physicians, aged 40-84 years. Blood samples were collected prior to randomization, mostly in 1982, from 14,916 participants, free from prior myocardial infarction (MI), stroke, or cancer (excluding non- melanoma skin cancer), and were stored at -82C. Using a nested case- control design, the plan is to continue to analyze the specimens for nutritional and biochemical/genetic markers of risk, with a specific focus on prostate and colorectal cancers. The studies are directed toward exploring the hypothesis that dietary and genetic factors, which increase intracellular folate, reduce risk of colon cancer. Measurements of biochemical markers (plasma, folate, vitamins B6 and B12), genetic polymorphisms for key enzymes, and dietary variables will be carried out. For both prostate and colorectal cancer, vitamin D levels and metabolism (including polymorphisms of the vitamin D receptor) will be assessed. Additional experiments will test the hypotheses that high levels of insulin-like growth factor (IGF) and low levels of selenium are associated with risk of colorectal and prostate cancer. These analyses are based in the PHS, for which follow-up of disease endpoints is already supported. Furthermore, there was a long period of beta-carotene supplementation for half the cohort, providing the opportunity to assess several interactions. The accrual of cases over a long duration since the blood was drawn will permit an assessment of latency. The completeness of follow-up and the many assays already performed can be used to complement any further studies. Several important and intriguing results have already emerged from the study. The nested case-control approach and the multiple analyses have provided an efficient means to increase the scientific value of PHS and test a number of hypotheses of potential public health importance, using blood samples that were collected at considerable expense and stored with great care.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Perloff, Marjorie
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Brigham and Women's Hospital
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FitzGerald, L M; Zhao, S; Leonardson, A et al. (2018) Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases. Prostate Cancer Prostatic Dis 21:228-237
Wang, Xiaoliang; Chan, Andrew T; Slattery, Martha L et al. (2018) Influence of Smoking, Body Mass Index, and Other Factors on the Preventive Effect of Nonsteroidal Anti-Inflammatory Drugs on Colorectal Cancer Risk. Cancer Res 78:4790-4799
Gu, Fangyi; Zhang, Han; Hyland, Paula L et al. (2017) Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia. Int J Cancer 141:1794-1802
Lindström, Sara; Finucane, Hilary; Bulik-Sullivan, Brendan et al. (2017) Quantifying the Genetic Correlation between Multiple Cancer Types. Cancer Epidemiol Biomarkers Prev 26:1427-1435
Yang, Meng; Ayuningtyas, Azalea; Kenfield, Stacey A et al. (2016) Blood fatty acid patterns are associated with prostate cancer risk in a prospective nested case-control study. Cancer Causes Control 27:1153-61
Karami, Sara; Han, Younghun; Pande, Mala et al. (2016) Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer 139:2655-2670
Phipps, Amanda I; Passarelli, Michael N; Chan, Andrew T et al. (2016) Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis. Carcinogenesis 37:87-95
Kocarnik, Jonathan M; Chan, Andrew T; Slattery, Martha L et al. (2016) Relationship of prediagnostic body mass index with survival after colorectal cancer: Stage-specific associations. Int J Cancer 139:1065-72
Zeng, Chenjie; Matsuda, Koichi; Jia, Wei-Hua et al. (2016) Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk. Gastroenterology 150:1633-1645
Kim, Chul; Zhang, Xuehong; Chan, Andrew T et al. (2016) Inflammatory biomarkers, aspirin, and risk of colorectal cancer: Findings from the physicians' health study. Cancer Epidemiol 44:65-70

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