Evaluation of genetic variants in association with colorectal cancer risk and survival in Asians. Issue 6 (21st June 2017)

• Record Type: Journal Article
• Authors: Wang, Nan; Lu, Yingchang; Khankari, Nikhil K.; Long, Jirong; Li, Hong‐Lan; Gao, Jing; Gao, Yu‐Tang; Xiang, Yong‐Bing; Shu, Xiao‐Ou; Zheng, Wei
• Is Part Of: International journal of cancer. Volume 141:Issue 6(2017:Sep. 15)
• Page Start: 1130
• Page End: 1139
• Publication Date: 2017-06-21
• Subjects: GWAS -- single nucleotide polymorphism -- colorectal cancer -- survival -- genetics -- review; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30812
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Genome‐wide association studies (GWAS) have identified over 40 genetic loci associated with colorectal cancer (CRC) risk. The association of single nucleotide polymorphisms (SNPs) at these loci with CRC risk and survival has not been adequately evaluated in East Asians. GWAS‐identified CRC risk variants were used to construct weighted genetic risk scores (GRSs). We evaluated these GRSs in association with CRC risk in 3, 303 CRC cases and 3, 553 controls using logistic regression models. Associations with overall and CRC‐specific survival were assessed in 731 CRC patients using Cox regression models. The association between the GRSs (overall and Asian‐specific) and CRC risk was approximately twofold (highest vs . lowest quintile), and the shape of the dose–response was linear ( p trend = 1.24 × 10 −13 and 3.02 × 10 −14 for overall GRS and Asian‐specific GRS, respectively). The association of the GRS with CRC risk was stronger among those with a family history of CRC ( p interaction = 0.007). Asian‐specific GRS using previously reported survival SNPs increased risk for mortality and the shape of the dose–response was linear for CRC‐specific and all‐cause mortality ( p trend = 0.01 and 0.006, respectively). Furthermore, the minor alleles of rs6983267 and rs1957636 were associated with worse CRC‐specific and overall survival. We show that GRSs constructed using GWAS‐identified common variants are strongly associated with CRC risk in Asians. We confirm previous findings for the possible association between some SNPs with survival, and provide evidence for two additional CRC risk variants that may be related to CRC survival. Abstract : What's new? While multiple genetic variants are associated with colorectal cancer (CRC) susceptibility, most have been investigated only in European descendants. By comparison, far less is known about CRC risk variants in Asian populations. To better understand relationships between CRC variants, risk, and survival in East Asians, the authors of the present study constructed weighted genetic risk scores (GRSs) from CRC risk variants identified in previous genome‐wide association studies. GRSs were strongly associated with CRC risk in patients with family history of the disease. In addition, two risk variants (rs6983267 and rs1957636) were associated specifically with worse CRC survival.