||5U01CA176726-07 Interpret this number
||Harvard School Of Public Health
||Life Course Cancer Epidemiology Cohort in Women
We propose to continue the follow-up of the Nurses' Health Study II (NHSII), a Cancer Epidemiology Cohort of
116,430 women enrolled at ages 25 to 42 years in 1989. The NHSII is a unique cohort in many ways, as the
only large cohort of women enrolled before menopause and with nearly 30 years of repeated measures of
exposures. We have information on smoking, weight, medication use, diet, physical activity and medical
diagnoses updated every two to four years. Further, we have collected detailed data on in utero and infant
exposures (from participants' mothers), diet during high school, and other unique exposure information. We
have nearly complete ascertainment of deaths using the National Death Index and other methods. The follow-
up of the NHSII cohort remains high, with 94% cumulative follow-up. The NHSII biorepository includes plasma,
red blood cells, white blood cells, and first morning urine samples from 29,611 women; two thirds of these
women contributed timed follicular and luteal premenopausal samples. In 2008 to 2011, 16,510 women
provided second blood and urine samples when the majority were postmenopausal. We also have cheek cell
DNA from an additional 29,859 women. Adding to these resources, we were recently funded to collect fecal
samples from 25,000 participants for microbiome analysis. We have collected archival tissue blocks for
incident breast and ovarian cancers and melanoma (approximately 70% of requests have been obtained), and
collections for other cancers are ongoing. Breast and ovarian cancer tissues have been utilized for gene
expression, and tissue microarrays are used extensively for immunohistochemistry. Prediagnostic
mammograms have been collected for breast cancer cases and controls, as well as pathology material from
previous biopsies of benign lesions. Substantial proportions of the cohort have GWAS and metabolomic data
from nested case-control analyses. This cohort has been highly productive; over 330 papers have been
published during the last five years, and the rate of publication is increasingly rapidly. With our active resource
sharing component, we have participated in 19 consortia as a member of the NCI Cohort Consortium, one of
the few cohorts contributing substantial data on premenopausal women and the largest contributor of
premenopausal breast cancers. We also have active data sharing collaborations with individual external
investigators. These external collaborations and consortia have resulted in more than 63 publications during
the current funding period. In the current proposal, we aim to continue cohort follow-up and maintain these
unique resources. We will continue collecting blood and urine samples from women with breast cancer who
also provided prediagnostic samples, tumor tissue for incident cancers, and pre-diagnostic pre- and
postmenopausal mammograms. We propose to conduct a long-term (2-3 year) reproducibility study for gut
microbiome. Finally, we will enhance our data management and analytic tools to maximize efficiency and use
of our complex resources to identify modifiable determinants of cancer incidence and survival.
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