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

R. Cui, Y. Okada, S. G. Jang, J. L. Ku, J. G. Park, Y. Kamatani, N. Hosono, T. Tsunoda, V. Kumar, C. Tanikawa, N. Kamatani, R. Yamada, Michiaki Kubo, Y. Nakamura, Koichi Matsuda

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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=7.92310-9, 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.

Original languageEnglish
Pages (from-to)799-805
Number of pages7
JournalGut
Volume60
Issue number6
DOIs
Publication statusPublished - 01-06-2011

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Colonic Neoplasms
Colorectal Neoplasms
Population
Genome-Wide Association Study
Alcohol Drinking
Single Nucleotide Polymorphism
Early Diagnosis
Japan

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Cui, R., Okada, Y., Jang, S. G., Ku, J. L., Park, J. G., Kamatani, Y., ... Matsuda, K. (2011). Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. Gut, 60(6), 799-805. https://doi.org/10.1136/gut.2010.215947
Cui, R. ; Okada, Y. ; Jang, S. G. ; Ku, J. L. ; Park, J. G. ; Kamatani, Y. ; Hosono, N. ; Tsunoda, T. ; Kumar, V. ; Tanikawa, C. ; Kamatani, N. ; Yamada, R. ; Kubo, Michiaki ; Nakamura, Y. ; Matsuda, Koichi. / Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. In: Gut. 2011 ; Vol. 60, No. 6. pp. 799-805.
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title = "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=7.92310-9, 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.",
author = "R. Cui and Y. Okada and Jang, {S. G.} and Ku, {J. L.} and Park, {J. G.} and Y. Kamatani and N. Hosono and T. Tsunoda and V. Kumar and C. Tanikawa and N. Kamatani and R. Yamada and Michiaki Kubo and Y. Nakamura and Koichi Matsuda",
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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 2011, 'Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population', Gut, vol. 60, no. 6, pp. 799-805. https://doi.org/10.1136/gut.2010.215947

Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. / Cui, R.; Okada, Y.; Jang, S. G.; Ku, J. L.; Park, J. G.; Kamatani, Y.; Hosono, N.; Tsunoda, T.; Kumar, V.; Tanikawa, C.; Kamatani, N.; Yamada, R.; Kubo, Michiaki; Nakamura, Y.; Matsuda, Koichi.

In: Gut, Vol. 60, No. 6, 01.06.2011, p. 799-805.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population

AU - Cui, R.

AU - Okada, Y.

AU - Jang, S. G.

AU - Ku, J. L.

AU - Park, J. G.

AU - Kamatani, Y.

AU - Hosono, N.

AU - Tsunoda, T.

AU - Kumar, V.

AU - Tanikawa, C.

AU - Kamatani, N.

AU - Yamada, R.

AU - Kubo, Michiaki

AU - Nakamura, Y.

AU - Matsuda, Koichi

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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=7.92310-9, 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.

AB - 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=7.92310-9, 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.

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Cui R, Okada Y, Jang SG, Ku JL, Park JG, Kamatani Y et al. Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. Gut. 2011 Jun 1;60(6):799-805. https://doi.org/10.1136/gut.2010.215947