Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper aerodigestive tract cancers in a Japanese population

Isao Oze, Keitaro Matsuo, Takeshi Suzuki, Takakazu Kawase, Miki Watanabe, Akio Hiraki, Hidemi Ito, Satoyo Hosono, Taijiro Ozawa, Shunzo Hatooka, Yasuhi Yatabe, Yasuhisa Hasegawa, Masayuki Shinoda, Katsuyuki Kiura, Kazuo Tajima, Mitsune Tanimoto, Hideo Tanaka

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50 Citations (Scopus)

Abstract

Alcohol intake is positivelyas sociated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover,UATcancer was significantlyassociated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations.We conducted a matched case-control studyto clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UATcancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed byodds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independentlyan d statisticallysignificant effects onUATcancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavydrinkers, heavysm okers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required.

Original languageEnglish
Pages (from-to)3097-3102
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 2009

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Oze, I., Matsuo, K., Suzuki, T., Kawase, T., Watanabe, M., Hiraki, A., Ito, H., Hosono, S., Ozawa, T., Hatooka, S., Yatabe, Y., Hasegawa, Y., Shinoda, M., Kiura, K., Tajima, K., Tanimoto, M., & Tanaka, H. (2009). Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper aerodigestive tract cancers in a Japanese population. Cancer Epidemiology Biomarkers and Prevention, 18(11), 3097-3102. https://doi.org/10.1158/1055-9965.EPI-09-0499