We propose to continue and extend the analysis of blood samples that were collected at baseline as part of the ongoing Physicians' Health Study (PHS), a randomized trial of aspirin and beta-carotene among 22,071 U.S. male physicians aged 40-84 years. The aspirin component of the trial was terminated in 1988 when a 44% reduction in myocardial infarction was observed in the aspirin group, but the beta-carotene component was recently extended for an additional five years. Blood samples were collected prior to randomization from 14,916 participants free from prior NH, stroke, or cancer (excluding nonmelanoma skin cancer), and were stored at -82 degrees C. Using a nested case-control design, we plan to continue to analyze the specimens for retinol, beta-carotene, other carotenoids, vitamin E, seleniura, lipids, and fatty acids. It is likely that any chemopreventive effect of beta-carotene will be modified by baseline blood levels, reflecting intake from dietary sources. If the anti-cancer activity of beta-carotene operates chiefly or solely among those with initially low blood levels, the trial may not have sufficient power to detect this effect, because that target group would not be identifiable. However, the proposed analyses will provide the opportunity to observe that effect. The primary aim of this project is therefore to enhance the power and interpretability of the PHS findings. For maximum utilization of the samples, we will also test a number of hypotheses relating blood levels of various nutrients listed above to risk of subsequent cancer, myocardial infarction, and stroke. We will analyze specimens for cases and controls individually matched for age and smoking. Several of these nutrients may have important interactions with beta-carotene as well as among themselves. We also plan to extend the analyses relating lipid fractions to myocardial infarction and stroke, and test several new hypotheses: homocysteine (and related nutrients, vitamin B12 and folate), and plasminogen activator inhibitor in relation to MI risk, and iron stores and risk of cancer. Several important and intriguing results have already emerged from the study. The nested case-control approach and the multiple analyses provide an efficient means to increase the scientific value of the PHS and test a number of hypotheses of potential public health importance, using blood samples that were collected at considerable expense.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
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
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
Yang, Meng; Sesso, Howard D; Colditz, Graham A et al. (2016) Effect Modification by Time Since Blood Draw on the Association Between Circulating Fatty Acids and Prostate Cancer Risk. J Natl Cancer Inst 108:
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

Showing the most recent 10 out of 150 publications