Research Abstract I - 2003
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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