Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese

Abstract

Genome-wide association studies (GWAS) have reported a number of loci harboring common variants that influence risk of colorectal cancer (CRC) in European descent. But all the SNPs identified explained a small fraction of total heritability. To identify more genetic factors that modify the risk of CRC, especially Chinese Han specific, we conducted a three-stage GWAS including a screening stage (932 CRC cases and 966 controls) and two independent validations (Stage 2: 1,759 CRC cases and 1,875 controls; Stage 3: 943 CRC cases and 1,838 controls). In the combined analyses, we discovered two novel loci associated with CRC: rs12522693 at 5q23.3 (CDC42SE2-CHSY3, OR = 1.31, P = 2.08 × 10−8) and rs17836917 at 17q12 (ASIC2-CCL2, OR = 0.75, P = 4.55 × 10−8). Additionally, we confirmed two previously reported risk loci, rs6983267 at 8q24.21 (OR = 1.17, P = 7.17 × 10−7) and rs10795668 at 10p14 (OR = 0.86, P = 2.96 × 10−6) in our cohorts. These results bring further insights into the CRC susceptibility and advance our understanding on etiology of CRC.

Japanese genome‐wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14

“…Tenesa et al (5) report the SNP rs3802842 at 11q23, rs7014346 at 8q24 and rs4939827 at 18q21. Table 1 shows the data derived from previous GWAS on CRC, (1,2,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) which reveal that risky genetic polymorphisms are different among various populations. For example, in the 8q23-24 region, rs6983267 is a risk factor for CRC among Caucasians, Asians and Africans, rs7014346 and rs10505477 are risky only among Caucasians, and rs16892766 is a risk factor for those with Caucasian and African ancestry.…”

Risk of eighteen genome-wide association study-identified genetic variants for colorectal cancer and colorectal adenoma in Han Chinese

“…Recently, a GWAS of colorectal cancer in East Asians [65] and two in Chinese (labeled as Chinese 1 [66] and Chinese 2 [67]) identified new novel loci for colorectal cancer risk. Most of our variants were included in the three GWAS (Supplementary Table S2).…”

Combinations of single nucleotide polymorphisms identified in genome‐wide association studies determine risk for colorectal cancer

“…After removing 22 individuals without complete demographic information, a total of 1,316 CRC patients and 2,207 controls were retained in Nanjing study for national colorectal cancer cohort (NCRCC). Additionally, 932 CRC patients and 966 controls were recruited from the Beijing GWAS study, the population details have been described in previous studies . The demographic characteristics are shown in Supporting Information Table S2.…”