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A common 8q24 variant in prostate and breast cancer from a large nested case-control study
Fredrick R Schumacher1, Heather Spencer Feigelson, David G Cox
1Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Cancer Research
|April 6, 2007
Summary
A common genetic marker, rs1447295, in the 8q24 region significantly increases prostate cancer risk in Caucasians. The association was also significant in African Americans with early-onset prostate cancer, but not breast cancer.
Area of Science:
- Genetics
- Oncology
- Epidemiology
Background:
- Recent studies identified 8q24 region polymorphisms, including single nucleotide polymorphism (SNP) rs1447295, associated with prostate cancer risk.
- The 8q24 region is a known susceptibility locus for prostate cancer.
Purpose of the Study:
- To replicate the association of the rs1447295 polymorphism with prostate cancer risk in a large nested case-control study.
- To investigate the association between rs1447295 and breast cancer risk.
- To examine potential differences in prostate cancer risk association by age at diagnosis and tumor characteristics.
Main Methods:
- A large nested case-control study utilizing data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
- Genotyping of the rs1447295 polymorphism in 6,637 prostate cancer cases and 7,361 controls, and 2,604 breast cancer cases and 3,118 controls.
- Statistical analysis to assess the association with prostate and breast cancer risk, and subgroup analyses by age at diagnosis, race, Gleason score, stage, and mortality.
Main Results:
- The rs1447295 marker showed a strong association with prostate cancer risk in Caucasians (P = 1.23 x 10(-13)).
- This association remained highly significant even after excluding specific cohort samples (P = 8.64 x 10(-13)).
- Carriers of one or two copies of the minor allele had significantly increased odds ratios for prostate cancer.
- The genotype association was significant in African Americans with early-onset prostate cancer (P = 0.011) but not later-onset.
- No significant association was found between rs1447295 and breast cancer risk (P = 0.590) or risk stratified by tumor characteristics.
Conclusions:
- The rs1447295 polymorphism is a robust genetic marker for prostate cancer risk, particularly in Caucasians.
- The association in African Americans may be influenced by age at diagnosis.
- The identified marker's strong validation supports its role in prostate cancer susceptibility, despite the responsible gene remaining unknown.
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