Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population.

Abstract:

BACKGROUND AND AIM:Colorectal cancer (CRC) is a multifactorial disease with both environmental and genetic factors contributing to its development. The incidence of CRC is increasing year by year in Japan. Patients with CRC in advanced stages have a poor prognosis, but detection of CRC at earlier stages can improve clinical outcome. Therefore, identification of epidemiologial factors that influence development of CRC would facilitate the prevention or early detection of disease. METHODS:To identify loci associated with CRC risk, we performed a genome-wide association study (GWAS) for CRC and sub-analyses by tumour location using 1583 Japanese CRC cases and 1898 controls. Subsequently, we conducted replication analyses using a total of 4809 CRC cases and 2973 controls including 225 Korean subjects with distal colon cancer and 377 controls. RESULTS:We identified a novel locus on 6q26-q27 region (rs7758229 in SLC22A3, p = 7.92 × 10⁻⁹, OR of 1.28) that was significantly associated with distal colon cancer. We also replicated the association between CRC and SNPs on 8q24 (rs6983267 and rs7837328, p = 1.51 × 10⁻⁸ and 7.44 × 10⁻⁸, ORs of 1.18 and 1.17, respectively). Moreover, we found cumulative effects of three genetic factors (rs7758229, rs6983267, and rs4939827 in SMAD7) and one environmental factor (alcohol drinking) which appear to increase CRC risk approximately twofold. CONCLUSIONS:We found a novel susceptible locus in SLC22A3 that contributes to the risk of distal colon cancer in an Asian population. These findings would further extend our understanding of the role of common genetic variants in the aetiology of CRC.

journal_name

Gut

journal_title

Gut

authors

Cui R,Okada Y,Jang SG,Ku JL,Park JG,Kamatani Y,Hosono N,Tsunoda T,Kumar V,Tanikawa C,Kamatani N,Yamada R,Kubo M,Nakamura Y,Matsuda K

doi

10.1136/gut.2010.215947

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

799-805

issue

6

eissn

0017-5749

issn

1468-3288

pii

gut.2010.215947

journal_volume

60

pub_type

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