Replication study of SNP associations for colorectal cancer in Hong Kong Chinese

Abstract

Background:Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC.Methods:An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs.Results:Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10−5).Conclusion:These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.

Single-nucleotide polymorphism associations for colorectal cancer in southern Chinese population

“…By contrast, this association was not significant in our subjects. For rs10795668, located on 10p14, there was no significant association with CRC risk, but its protective effect was similar to that described in previous studies [4,10,15] . Furthermore, this SNP was shown to be associated with CRC in a northern Chinese population [9] but not in our subjects.…”

“…However, all of these studies were conducted in Caucasians, with only one replicated in a Japanese population [5] . More recently, the association between several loci identified in GWAS for CRC was confirmed in a northern Han Chinese population [9] and in Hong Kong Chinese [10] Subjects . Here, we examined the impact of 11 previously reported loci in a Han Chinese population in Jiangxi Province, Southern China.…”

“…Eleven of the most significantly associated SNPs were selected, seven loci (rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, and rs3802842) had been identified in GWAS [3][4][5][6][7][8][9][10] and four (rs4444235, rs9929218, rs10411210, and rs961253) in meta-analyses based on GWAS data [11] . Table 2 shows these loci and the respective references.…”

Intronic Polymorphisms of the SMAD7 Gene in Association with Colorectal Cancer

“…On the other hand, Slattery M.L., et al couldn't find any significant association between rs4464148 and CRC susceptibility even when laminated them by age, tumor site or family history (Slattery et al, 2010). Furthermore, in two distinguished researches that have been investigated in Asia, same results have been accomplished (Ho et al, 2011;Li et al, 2011).…”

“…To the best of our knowledge, several studies corroborated the role of rs12953717 polymorphism in cancer susceptibility (Broderick et al, 2007;Tomlinson et al, 2008;Curtin et al, 2009;Middeldorp et al, 2009;Pittman et al, 2009;Slattery et al, 2010;Ho et al, 2011;Li et al, 2011). According to previous cancer-susceptibilitystudies which mainly revealed the remarkable association between the SMAD7 SNP and the risk of CRC, our study demonstrated that allele T at rs12953717 can increase the risk of CRC.…”