A common genetic risk factor for colorectal and prostate cancer

Abstract

Variants on chromosome 8q24 contribute risk for prostate cancer; here, we tested whether they also modulate risk for colorectal cancer. We studied 1,807 affected individuals and 5,511 controls and found that one variant, rs6983267, is also significantly associated with colorectal cancer (odds ratio = 1.22; P = 4.4 x 10(-6)) and that the apportionment of risk among the variants differs significantly between the two cancers. Comprehensive testing in the region uncovered variants capturing significant additional risk. Our results show that variants at 8q24 have different effects on cancer development that depend on the tissue type.

Figure 1

Fine mapping in the region 128.47–128.54 Mb of 8q24. We present data for 82 SNPs that we genotyped in 1,088 individuals with CRC and 1,823 controls. These SNPs capture ≥92% of SNPs of >5% minor allele frequency at r² > 0.8 in HapMap populations (Supplementary Fig. 2). (a) The most strongly associated SNP is rs10808556 (red), P = 2.2 × 10⁻⁶, which is substantially more associated than rs6983267 (green), the SNP that initially led us to the region (P = 2.4 × 10⁻⁴). (b) Controlling for rs10808556 in a logistic regression analysis, no SNP is significant at P < 0.05 after correcting for 82 hypotheses tested (threshold shown by a light gray line).