This article is part of the supplement: The Framingham Heart Study 100,000 single nucleotide polymorphisms resource
A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study
1 The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA
2 Section of General Internal Medicine and the Sections of Hematology/Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
3 National Heart, Lung, and Blood Institute, Bethesda, MD, USA
BMC Medical Genetics 2007, 8(Suppl 1):S6 doi:10.1186/1471-2350-8-S1-S6Published: 19 September 2007
Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified.
We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits – prostate cancer and breast cancer – in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT).
There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 × 10-8 in COL1A1; and prostate cancer, rs9311171, p = 1.75 × 10-6 in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.
Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility.