Original BPC3 Research Plan

Breast and Prostate Cancer and Hormone-Related Gene Variant Study

The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism. The study combines the resources of six large prospective cohorts from the American Cancer Society (Cancer Prevention Study-II (CPS)), Harvard University (Harvard Cohort Studies), the International Agency for Research on Cancer (European Prospective Investigation into Cancer and Nutrition (EPIC) Study), and the Universities of Hawaii and Southern California (Multiethnic Cohort Study). In addition, two NCI intramural cohorts (Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study are participating.

The study is unique in having prospective plasma samples, genetic material, anthropometric measurements, and extensive questionnaire data on diet, physical activity, exogenous hormone use, smoking, and other lifestyle factors from over 740,000 men and women. Data are drawn from 8,850 patients with prostate cancer and 6,160 patients with breast cancer. Because of the scope and collaborative nature of this consortium, simultaneous investigation of genetic predisposition and lifestyle factors is possible to clarify the inter-relationships between, and the relative importance of, genetic and hormonal risk factors.

Specifically, this study is defining SNPs and haplotypes in steroid hormone metabolizing genes, genes in the insulin-like growh factor (IGF) pathway, and related receptor proteins. These candidate genes are being resequenced in 96 cases of advanced breast cancer, and 96 cases of advanced prostate cancer chosen from the European, African, Latino, Japanese, and Hawaiian-origin ethnic groups. Haplotype tag SNPs are being selected after genotyping of a larger number of SNPs from a collection of 768 samples from the multigenerational CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees and human diversity collection, by the Whitehead Institute for Genome Research and CEPH, and are rapidly being made publicly available.

The interaction of genetic variants with hormonal, lifestyle, and anthropometric factors known to be associated with breast and prostate cancer are being examined. In a subset of studies, the association of these variants with markers of breast and prostate cancer risk (i.e., plasma steroid hormone levels and IGF-1 levels) are being investigated.

Projects developed within the study are fostering continuing interactions between the genomic and epidemiologic research communities, and are integrating the rapid advances in genomic research into large-scale epidemiologic studies. The ultimate goal is to provide the foundation for reducing the public health burden of these cancers.

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