Background: Genome-wide association studies have identified several colorectal cancer (CRC) genetic risk factors. However, these studies have been performed primarily in individuals of European descent and none include African Americans (AAs). Determining CRC genetic risk factors in AAs is important because CRC incidence and mortality rates are highest of all US populations.

Aim: To validate genome-wide CRC genetic risk factors, we tested single nucleotide polymorphism (SNP) associations in ten chromosome (chr) regions in AAs and European-Americans (EAs).

Methods: We genotyped 22 SNPs in 1725 AA and 883 EA CRC cases and controls using Sequenom iPLEX. Ancestry estimates were obtained using STRUCTURE 2.1. We tested for allelic association and calculated odds ratios and confidence intervals using logistic regression adjusting for ancestry, age and gender.

Results: Association results are shown in the Table. In AAs, rs10795668 (chr 10) and rs10318 (chr 15) were significantly associated with CRC. rs7014346 (chr 8) and rs355527 (chr 20) trended toward significant associations. In EAs, three SNPs on chr 8 were significantly associated with CRC. In addition, two chr 11 SNPs (rs3802842 & rs1074997) and rs1862748 (chr 16) were significantly associated with disease in EAs. SNPs on chr 15 and chr 16 are located in or near genes GREM1 and CDH1 respectively. SNPs on chr 8, 10, 11 and 20 are in gene deserts.

Conclusion: This is the first study to validate genome-wide SNP associations in AAs. We also confirm several associations in EAs. SNPs on chr 15 & 16 are located in genes involved in TGFβ signaling (GREM1 & CDH1) which has been implicated in CRC pathogenesis, while those on chr 8, 10, 11 and 20 are in gene deserts. Future fine-mapping in these regions is warranted to identify functional variants.

Genome-wide SNP associations in African- and European-Americans

Chr (gene)SNPReference alleleAllele frequency casesAllele frequency controlsOR [95% CI]p*
African Americans             
rs7014346 0.42 0.39 1.14 [0.99-1.31] 0.07 
10 rs10795668 0.08 0.06 1.41 [1.07-1.87] 0.04 
15 (GREM1) rs10318 0.05 0.03 1.45 [1.02-2.05] 0.05 
20 rs355527 0.18 0.20 0.87 [0.73-1.04] 0.09 
European Americans             
rs6983626 0.12 0.09 1.38 [1.00-1.91] 0.05 
rs6983267 0.52 0.47 1.24 [1.01-1.51] 0.04 
rs7837328 0.43 0.37 1.30 [1.06-1.60] 0.01 
11 rs3802842 0.33 0.28 1.26 [1.02-1.57] 0.02 
11 rs10749971 0.41 0.33 1.42 [1.15-1.74] 0.0002 
16 (CDH1) rs1862748 0.28 0.32 0.80 [0.64-0.99] 0.04 
Chr (gene)SNPReference alleleAllele frequency casesAllele frequency controlsOR [95% CI]p*
African Americans             
rs7014346 0.42 0.39 1.14 [0.99-1.31] 0.07 
10 rs10795668 0.08 0.06 1.41 [1.07-1.87] 0.04 
15 (GREM1) rs10318 0.05 0.03 1.45 [1.02-2.05] 0.05 
20 rs355527 0.18 0.20 0.87 [0.73-1.04] 0.09 
European Americans             
rs6983626 0.12 0.09 1.38 [1.00-1.91] 0.05 
rs6983267 0.52 0.47 1.24 [1.01-1.51] 0.04 
rs7837328 0.43 0.37 1.30 [1.06-1.60] 0.01 
11 rs3802842 0.33 0.28 1.26 [1.02-1.57] 0.02 
11 rs10749971 0.41 0.33 1.42 [1.15-1.74] 0.0002 
16 (CDH1) rs1862748 0.28 0.32 0.80 [0.64-0.99] 0.04 

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4734.