Abstract
Background: Genome-wide association studies of colorectal cancer (CRC) have identified risk variants in 10 genomic regions. None of these studies included African Americans, who have the highest incidence and mortality from CRC in the U.S. For the 10 genomic regions, we performed an association study in African and European Americans. Methods: We genotyped 22 single nucleotide polymorphisms (SNPs) in DNA samples from 1194 patients with CRC (795 African Americans and 399 European Americans) and 1352 controls (985 African Americans and 367 European Americans). At chromosome 8q24.21 region 3, we analyzed five additional SNPs from 1000 African American cases and 1393 controls. Association testing was done using multivariate logistic regression controlling for ancestry, age, and sex.
Results: Whereas effects sizes and directions of association for all SNPs tested in European Americans were consistent with previously published studies, the associations ran in the opposite direction for 9 of 22 SNPs tested in African Americans. Among African Americans, the SNP rs6983267 at 8q24.21 was not associated with CRC (OR=1.18; P=0.12); instead, the 8q24.21 SNP rs7014346 (OR=1.15; p=0.03) was associated with CRC in this population. On chromosome 15q13.3, rs10318 was associated with CRC in both populations. On chromosome 10p14, the opposite allele of rs10795668 was associated with CRC in African Americans (OR=1.35; P=0.04). On chromosome 11 q23.1, rs3802842 was significantly associated with rectal cancer risk only among African Americans (OR 1.34; P=0.01); a similar observation was made in previous studies of Europeans. Among European Americans, SNPs on chromosomes 8q24.21,11 q23.1, and 16q22.1 were associated with CRC, in agreement with previous reports.
Conclusion: There is genetic heterogeneity in CRC associations in Americans of African vs. European descent.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-4.
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