Diet is a risk factor for many cancers. However, the appropriate latent period for dietary risk factors is unknown. A strength of the NHS database is the availability of repeat dietary information over 30+ years. One goal of this application (aim 1) is to obtain optimal methods of weighting repeated measures of diet over a 30 year period using an exponential smoothing weighting function. This approach will also be applied to non-dietary exposures such as cigarette smoking and hormone use over a long period of time. Another innovation in cancer epidemiology is the availability of multiple tumor markers which can refine the epidemiology of specific cancers according to tumor type, and help confirm the causality of an association. However, as the number of tumor markers gets large, the number of subsets of tumors also gets large.
In aim 2, we propose survival analysis methods to estimate the 2-way interaction between risk factors and tumor types as well as 3-way interactions between risk factors and combinations of tumor types. Improvements in cancer risk prediction are increasingly occurring with novel risk factors measured in case-control datasets.
Aim 3 of this application combines information on novel risk factors in case/control datasets with standard risk factors in prospective datasets to improve risk prediction. For breast cancer, an Important predictor is age at menopause. However, this is only known for women with natural menopause and bilateral oophorectomy.
In aim 4, we seek to estimate age at natural menopause among other surgical menopause women to reduce bias and enhance precision of breast cancer risk prediction.
In aim 5, we will extend the colon cancer risk prediction model developed in the previous cycle of this grant, by developing separate models for proximal cancer, distal cancer and rectal cancer. We also consider novel methods of analysis of recurrent colorectal adenoma outcome data using interval censored survival methods. This Project will interact closely with Projects 1-3 to improve our understanding of the etiology of breast, colorectal and ovarian cancers in women. It also shares with the other Projects a strong administrative and scientific infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis).

Public Health Relevance

This project is aimed at developing methods for refining cancer risk prediction in different ways: efficient use of time dependent covariates, estimation of risk profiles defined by tumor markers and combining risk factor information from case/control and prospective datasets.The overall goal of this project is to refine data analysis technique used in cancer epidemiology which will aid in etiology as well as in identifying women who truly are at high risk for breast, colorectal and ovarian cancer.

National Institute of Health (NIH)
Research Program Projects (P01)
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Brigham and Women's Hospital
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Sparks, Jeffrey A; Chen, Chia-Yen; Jiang, Xia et al. (2015) Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann Rheum Dis 74:1522-9
Ananthakrishnan, Ashwin N; Du, Mengmeng; Berndt, Sonja I et al. (2015) Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies. Cancer Epidemiol Biomarkers Prev 24:198-205
Tworoger, Shelley S; Rice, Megan S; Rosner, Bernard A et al. (2015) Bioactive prolactin levels and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 24:73-80
Song, Mingyang; Gong, Jian; Giovannucci, Edward L et al. (2015) Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer 137:154-64
Merola, Joseph F; Wu, Shaowei; Han, Jiali et al. (2015) Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis 74:1495-500
Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko et al. (2015) Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol 22:1226-35
Bertrand, Kimberly A; Rosner, Bernard; Eliassen, A Heather et al. (2015) Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149:479-87
Zhou, Jiachen; Kelsey, Karl T; Giovannucci, Edward et al. (2014) Fluid intake and risk of bladder cancer in the Nurses' Health Studies. Int J Cancer 135:1229-37
Li, Shanshan; Flint, Alan; Pai, Jennifer K et al. (2014) Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study. BMJ 348:g2659
Sun, Qi; Jiménez, Monik C; Townsend, Mary K et al. (2014) Plasma levels of fetuin-A and risk of coronary heart disease in US women: the Nurses' Health Study. J Am Heart Assoc 3:e000939

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