Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population
- R Cui1,
- Y Okada2,
- S G Jang3,
- J L Ku3,
- J G Park3,
- Y Kamatani1,
- N Hosono4,
- T Tsunoda5,
- V Kumar1,
- C Tanikawa1,
- N Kamatani6,
- R Yamada2,
- M Kubo4,
- Y Nakamura1,7,
- K Matsuda1
- 1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- 2Laboratory of Functional Genomics, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- 3Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
- 4Laboratory for Genotyping Development, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
- 5Laboratory for Medical Informatics, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
- 6Laboratory for Statistical Analysis, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
- 7Laboratory for International Alliance, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
- Correspondence to Dr Koichi Matsuda, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan;
Contributors YN conceived the study; YN, RC, MK and KM designed the study; RC, S-GJ, VK, CT and NH performed the genotyping; RC, YN and KM wrote the manuscript; RC, YO, YK, TT, RY and NK performed data analysis at the genome-wide phase; J-LK, J-GP, YN, KM and MK managed the DNA samples.
- Revised 1 November 2010
- Accepted 8 November 2010
- Published Online First 17 January 2011
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.
Funding This study was funded by the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Competing interests None.
Ethics approval This project was approved by the ethics committees at the Institute of Medical Science, the University of Tokyo, the Center for Genomic Medicine (formerly, SNP Research Center), Institutes of Physical and Chemical Research (RIKEN), and Seoul National University College of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.
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