Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan

Guang Yin, Makiko Morita, Keizo Ohnaka, Kengo Toyomura, Nobuyuki Hamajima, Tetsuya Mizoue, Takashi Ueki, Masao Tanaka, Yoshihiro Kakeji, Yoshihiko Maehara, Takeshi Okamura, Koji Ikejiri, Kitaroh Futami, Yohichi Yasunami, Takefumi Maekawa, Kenji Takenaka, Hitoshi Ichimiya, Reiji Terasaka

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Abstract

Background: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. Methods: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. Results: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). Conclusions: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalJournal of epidemiology
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 12 2012

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Genetic Polymorphisms
Alcohol Drinking
Colorectal Neoplasms
Japan
X-Rays
Genotype
Carcinogenesis
Alleles
Odds Ratio
Poisons
DNA Repair
Genes
DNA Damage
Case-Control Studies
Adenocarcinoma
Alcohols

All Science Journal Classification (ASJC) codes

  • Epidemiology

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Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan. / Yin, Guang; Morita, Makiko; Ohnaka, Keizo; Toyomura, Kengo; Hamajima, Nobuyuki; Mizoue, Tetsuya; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takefumi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji.

In: Journal of epidemiology, Vol. 22, No. 1, 12.01.2012, p. 64-71.

Research output: Contribution to journalArticle

Yin, G, Morita, M, Ohnaka, K, Toyomura, K, Hamajima, N, Mizoue, T, Ueki, T, Tanaka, M, Kakeji, Y, Maehara, Y, Okamura, T, Ikejiri, K, Futami, K, Yasunami, Y, Maekawa, T, Takenaka, K, Ichimiya, H & Terasaka, R 2012, 'Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan', Journal of epidemiology, vol. 22, no. 1, pp. 64-71. https://doi.org/10.2188/jea.JE20110059
Yin, Guang ; Morita, Makiko ; Ohnaka, Keizo ; Toyomura, Kengo ; Hamajima, Nobuyuki ; Mizoue, Tetsuya ; Ueki, Takashi ; Tanaka, Masao ; Kakeji, Yoshihiro ; Maehara, Yoshihiko ; Okamura, Takeshi ; Ikejiri, Koji ; Futami, Kitaroh ; Yasunami, Yohichi ; Maekawa, Takefumi ; Takenaka, Kenji ; Ichimiya, Hitoshi ; Terasaka, Reiji. / Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan. In: Journal of epidemiology. 2012 ; Vol. 22, No. 1. pp. 64-71.
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abstract = "Background: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. Methods: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. Results: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95{\%} CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95{\%} CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95{\%} CI 1.02-2.87) and 1.57 (95{\%} CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). Conclusions: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.",
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T1 - Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan

AU - Yin, Guang

AU - Morita, Makiko

AU - Ohnaka, Keizo

AU - Toyomura, Kengo

AU - Hamajima, Nobuyuki

AU - Mizoue, Tetsuya

AU - Ueki, Takashi

AU - Tanaka, Masao

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

AU - Okamura, Takeshi

AU - Ikejiri, Koji

AU - Futami, Kitaroh

AU - Yasunami, Yohichi

AU - Maekawa, Takefumi

AU - Takenaka, Kenji

AU - Ichimiya, Hitoshi

AU - Terasaka, Reiji

PY - 2012/1/12

Y1 - 2012/1/12

N2 - Background: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. Methods: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. Results: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). Conclusions: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

AB - Background: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. Methods: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. Results: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). Conclusions: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

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