Genetic Heterogeneity in Colorectal Cancer Associations Between African and European Americans
Background & Aims
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 United States. For the 10 genomic regions, we performed an association study of Americans of African and European descent.
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 6 SNPs from 1000 African American cases and 1393 controls. Association testing was done using multivariate logistic regression controlling for ancestry, age, and sex.
Results
Among African Americans, the SNP rs6983267 at 8q24.21 was not associated with CRC (odds ratio, 1.18; P = .12); instead, the 8q24.21 SNP rs7014346 (odds ratio, 1.15; P = .03) was associated with CRC in this population. At 15q13.3, rs10318 was associated with CRC in both populations. At 11q23.1, rs3802842 was significantly associated with rectal cancer risk only among African Americans (odds ratio, 1.34; P = .01); this observation was made in previous studies. Among European Americans, SNPs at 8q24.21, 11q23.1, and 16q22.1 were significantly associated with CRC, and the odds ratios were of the same magnitude and direction for all SNPs tested, consistent with previously published studies. In contrast, in African Americans, the opposite allele of rs10795668 at 10p14 was associated with colorectal cancer (odds ratio, 1.35; P = .04), and altogether the odds ratios were in the opposite direction for 9 of the 22 SNPs tested.
Conclusions
There is genetic heterogeneity in CRC associations in Americans of African versus European descent.
Keywords: Colon Cancer, Rectal Cancer, Ethnicity, Genetic Polymorphism
Abbreviations used in this paper: AIM, ancestry informative markers, CRC, colorectal cancer, GWAS, genome–wide association studies, HWE, Hardy–Weinberg equilibrium, LD, linkage disequilibrium, SNP, single nucleotide polymorphism, UC, University of Chicago, UNC, University of North Carolina
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by The Cancer Research Foundation, the Department of Medicine at the University of Chicago, the Digestive Disease Research Core Center (P30 DK42086), an American Cancer Society Institutional research grant, the University of Chicago Comprehensive Cancer Research Center and Clinical Translational Science Award, the University of North Carolina Digestive Disease Research Core Center (P30 DK34987), and grants from the National Cancer Institute (R01 CA66635) to R.S.S., U01 CA153060 to N.A.E., and K08 CA142892 to S.S.K. This report is solely the opinion of the authors and does not represent the official views of the National Cancer Institute or the National Institutes of Health.
PII: S0016-5085(10)01101-7
doi:10.1053/j.gastro.2010.07.038
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
