Grant Details
Grant Number: |
2U01CA176726-11 Interpret this number |
Primary Investigator: |
Willett, Walter |
Organization: |
Harvard School Of Public Health |
Project Title: |
Life Course Cancer Epidemiology Cohort in Women |
Fiscal Year: |
2023 |
Abstract
Project Summary 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 over 30 years of
repeated measures of exposures. We have information on smoking, weight, medication use, diet, physical
activity, environmental GIS-based exposures, 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 active follow-up of the NHSII cohort remains high, with 88%
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 recently collected fecal and oral samples from nearly 20,000 participants for microbiome
analysis. We have collected archival tissue blocks for incident breast, ovarian, colorectal, endometrial cancers,
and lymphomas and melanoma, as well as benign breast and colon lesions (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. Pre-
diagnostic mammograms have been collected for breast cancer cases and controls. Substantial proportions of
the cohort have GWAS and metabolomic data from nested case-control analyses. This cohort has been highly
productive; over 400 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 32 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 many individual external investigators. These external collaborations and consortia have
resulted in more than 75 cancer 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 pre-diagnostic samples, tumor tissue for incident
cancers, and pre-diagnostic pre- and postmenopausal mammograms. We propose to conduct a long-term (2-3
year) reproducibility analysis for genetic sequencing of gut microbiome samples. Finally, we will enhance our
data management and analytic tools to maximize efficiency and data sharing.
Publications