A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study.
BACKGROUND
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.


METHODS
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 > or =80%, minor allele frequency > or =10%, Hardy-Weinberg test p > or = 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT).


RESULTS
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 x 10(-8) in COL1A1; and prostate cancer, rs9311171, p = 1.75 x 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.


CONCLUSIONS
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.
Murabito
Joanne M
JM
The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA. murabito@bu.edu
Rosenberg
Carol L
CL
Finger
Daniel
D
Kreger
Bernard E
BE
Levy
Daniel
D
Splansky
Greta Lee
GL
Antman
Karen
K
Hwang
Shih-Jen
SJ
D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics*; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000150:complications / Q000235:genetics*