Genetic Heterogeneity in Colorectal Cancer Associations in Americans of African vs. European Descent

Sonia S. Kupfer
- Department of Medicine, Section of Gastroenterology University of Chicago Medical Center, Chicago, IL
Jeffrey R. Anderson
- Department of Medicine, Section of Gastroenterology University of Chicago Medical Center, Chicago, IL
Stanley Hooker
- Department of Medicine, Section of Genetic Medicine University of Chicago Medical Center, Chicago, IL
Andrew Skol
- Department of Medicine, Section of Genetic Medicine University of Chicago Medical Center, Chicago, IL
Rick A. Kittles
- Department of Medicine, Section of Genetic Medicine University of Chicago Medical Center, Chicago, IL
Temitope O. Keku
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC
Robert S. Sandler
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC
Nathan A. Ellis
- Department of Medicine, Section of Gastroenterology University of Chicago Medical Center, Chicago, IL
- Correspondence to: Nathan A. Ellis, Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, 900 East 57^th Street, 9^th floor, Chicago, IL 60637, (773) 834-2271 office. (773) 702-2281.

Received 1 April 2010; received in revised form 14 June 2010; accepted 16 July 2010. published online 26 July 2010.
Accepted Manuscript

Abstract

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 US. 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:

Sizes and directions of association for all SNPs tested in European Americans were consistent with previously published studies, but for 9 of 22 SNPs tested in African Americans, they were of an opposite direction. Among African Americans, the SNP rs6983267 at 8q24.21 was not associated with CRC (odds ratio [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. At 15q13.3, rs10318 was associated with CRC in both populations. At 10p14, the opposite allele of rs10795668 was associated with CRC in African Americans (OR=1.35; P=0.04). At 11q23.1, rs3802842 was significantly associated with rectal cancer risk only among African Americans (OR 1.34; P=0.01); this observation was made in previous studies. Among European Americans, SNPs at 8q24.21, 11q23.1, and 16q22.1 were associated with CRC, in agreement with previous reports.