Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1999 Jul;90(7):711–719. doi: 10.1111/j.1349-7006.1999.tb00805.x

Genotype Difference of Aldehyde Dehydrogenase 2 Gene in Alcohol Drinkers Influences the Incidence of Japanese Colorectal Cancer Patients

Motoi Murata 1,✉, Masatoshi Tagawa 2, Satoshi Watanabe 3, Hideki Kimura 4, Tatsuya Takeshita 5, Kanehisa Morimoto 5
PMCID: PMC5926133  PMID: 10470282

Abstract

A case‐control study was conducted to explore the possible etiologic role of alcohol and aldehyde dehydrogenase 2 (ALDH2) gene among Japanese colorectal cancer patients. Information on their drinking, smoking and dietary habits was collected from 265 colon and 164 rectum cancer patients, and 794 non‐cancer patients as a control group. Genotypes of the ALDH2 gene at codon 487, glutamic acid (ALDH2*1)as a wild‐type or lysine (ALDH2*2)as a mutated type with reduced enzyme activity, were analyzed by polymerase chain reaction in 160 colon and 110 rectum cancer patients and 121 control persons. Univariate analysis with the χ2 statistical test showed that heavy alcohol drinking (P < 0.01), frequent meat intake (P < 0.001), and irregular (P < 0.01), hasty (P < 0.01) and excessive (P <0.001) eating habits were associated with the incidence of both colon and rectum cancers, whereas heavier smoking (P < 0.05) and infrequent fish (P < 0.03)and fruit (P < 0.01) intake were solely associated with incidence of rectum cancer. Infrequent green vegetable intake was not correlated with the incidence of colorectal cancer. Multivariate unconditional logistic regression analysis confirmed the association of alcohol consumption (P < 0.01) and meat intake (P < 0.05). Homozygous and heterozygous carriers of ALDH2*2 allele tended to be found in colon (trend P= 0.04)but not in rectum cancer patients compared to controls. Risk elevation for colon cancer due to alcohol consumption was pronounced among the heterozygotes and it was statistically significant especially for distal colon cancer (trend P=0.02). We conclude that alcohol consumption is a risk factor for colorectal cancer and the risk can be enhanced in ALDH2 heterozygotes.

Keywords: Colorectal cancer, Alcohol drinking, ALDH2 genotype

Full Text

The Full Text of this article is available as a PDF (87.1 KB).

REFERENCES

  • 1).Blot , W. J.Alcohol and cancer . Cancer Res. , 52 , 2119s – 2123s ( 1992. ). [PubMed] [Google Scholar]
  • 2).Longnecker , M. P. , Orza , M. J. , Adams , M. E. , Vioque , J. and Chalmers , T. C.A meta‐analysis of alcoholic beverage consumption in relation to risk of colorectal cancer . Cancer Causes Control , 1 , 59 – 68 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 3).Kune , G. A. and Vitetta , L.Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991 . Nutr. Cancer , 18 , 92 – 111 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 4).Barra , S. , Negri , E. , Franceschi , S. , Guarneri , S. and Vecchia , C. L.Alcohol and colorectal cancer: a case‐control study from northern Italy . Cancer Causes Control , 3 , 153 – 159 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5).Meyer , F. and White , E.Alcohol and nutrients in relation to colon cancer in middle‐aged adults . Am. J. Epidemiol. 138 , 225 – 236 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 6).Newcomb , P. A. , Storer , B. E. and Marcus , P. M.Cancer of the large bowel in women in relation to alcohol consumption: a case‐control study in Wisconsin (United States) . Cancer Causes Control , 4 , 405 – 411 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 7).Goldbohm , R. A. , Van den Brandt , P. A. , van 't Veer , P. , Dorant , E. , Sturmans , F. and Hermus , R. J. J.Prospective study on alcohol consumption and the risk of cancer of the colon and rectum in the Netherlands . Cancer Causes Control , 5 , 95 – 104 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 8).Boutron , M. C. , Faivre , J. , Dop , M. C. and Senesse , P.Tobacco, alcohol, and colorectal tumors: a multistep process . Am. J. Epidemiol. , 141 , 1038 – 1046 ( 1995. ). [PubMed] [Google Scholar]
  • 9).Glynn , S. A. , Albanes , D. , Pietinen , P. , Brown , C. C. , Rautalahti , M. , Tangrea , J. A. , Taylor , P. R. and Virtamo , J.Alcohol consumption and risk of colorectal cancer in a cohort of Finnish men . Cancer Causes Control , 7 , 214 – 223 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 10).Le Marchand , L. , Wilkens , L. R. , Kolonel , L. N. , Hankin , J. H. and Lyu , L.Association of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer . Cancer Res. , 57 , 4787 – 4794 ( 1997. ). [PubMed] [Google Scholar]
  • 11).Thun , M. J. , Peto , R. , Lopez , A. D. , Monaco , J. H. , Henley , J. , Heath , C. W. and Doll , R.Alcohol consumption and mortality among middle‐aged and elderly U.S. adults . N. Engl. J. Med. , 337 , 1705 – 1714 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 12).Slattery , M. L. , Schaffer , D. , Edwards , S. L. , Ma , K. N. and Potter , J. D.Are dietary factors involved in DNA methylation associated with colon cancer ? Nutr. Cancer , 28 , 52 – 62 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 13).Tavani , A. , Ferraroni , M. , Mezzetti , M. , Franceschi , S. , Lo Re , A. and LaVecchia , C.Alcohol intake and risk of cancers of the colon and rectum . Nutr. Cancer , 30 , 213 – 219 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 14).Hirayama , T.Association between alcohol consumption and cancer of the sigmoid colon: observation from a Japanese cohort study . Lancet , ii , 725 – 727 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 15).Yoshida , K. , Oku , T. , Ohba , S. , Masuoka , H. , Watabe , K. , Mukaiya , M. , Sasaki , K. , Tsutsumi , T. , Hirata , K. , Mitsuhashi , Y. , Takeida , K. , Nishi , M. , Miyake , H. and Mori , M.A case‐control study of colorectal cancer: association between smoking, drinking, family history of cancer and colorectal cancer . Jpn. J. Cancer Clin. , 38 , 371 – 378 ( 1992. ) ( in Japanese ). [Google Scholar]
  • 16).Murata , M. , Takayama , K. , Choi , B. C. K. and Pak , A. W. P.A nested case‐control study on alcohol drinking, tobacco smoking, and cancer . Cancer Detect. Prev. , 20 , 557 – 568 ( 1996. ). [PubMed] [Google Scholar]
  • 17).Yamada , K. , Araki , S. , Tamura , M. , Sakai , I. , Takahashi , Y. , Kashihara , H. and Kono , S.Case‐control study of colorectal carcinoma in situ and cancer in relation to cigarette smoking and alcohol use (Japan) . Cancer Causes Control , 8 , 780 – 785 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 18).Chyou , P. H. , Nomura , A. M. and Stemmermann , G. N.A prospective study of colon and rectum cancer among Hawaii Japanese men . Ann. Epidemiol. , 6 , 276 – 282 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 19).Goedde , H. W. , Harada , S. and Agarwal , D. P.Racial differences in alcohol sensitivity: a new hypothesis . Hum. Genet. , 5 , 331 – 334 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 20).Takeshita , T. , Morimoto , K. , Mao , K. , Hashimoto , T. and Furuyama , J.Phenotypic differences in low Km aldehyde dehydrogenase in Japanese workers . Lancet , 341 , 837 – 838 ( 1993. ). [PubMed] [Google Scholar]
  • 21).Takeshita , T. , Morimoto , K. , Mao , X. , Hashimoto , T. and Furuyama , J.Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population . Hum. Genet. , 94 , 217 – 223 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 22).Yokoyama , A. , Muramatsu , T. , Ohmori , T. , Higuchi , S. , Hayashida , M. and Ishii , H.Esophageal cancer and aldehyde dehydrogenase‐2 genotypes in Japanese males . Cancer Epidemiol. Biomarkers Prev. , 5 , 99 – 102 ( 1996. ). [PubMed] [Google Scholar]
  • 23).Yokoyama , A. , Ohmori , T. , Muramatsu , T. , Higuchi , S. , Yokoyama , T. , Matsushita , S. , Matsumoto , M. , Maruyama , K. , Hayashida , M. and Ishii , H.Cancer screening of upper aerodigestive tract in Japanese alcoholics with reference to drinking and smoking habits and aldehyde dehydrogenase‐2 genotypes . Int. J. Cancer , 68 , 313 – 316 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 24).Rothman , K. L. and Boice , J. D. , Jr. “ Epidemiologic Analysis with a Programmable Calculator ” pp . 5 – 10 ( 1982. ). Epidemiology Resources Inc. , Boston . [Google Scholar]
  • 25).Breslow , N. E. and Day , N. E. “ Statistical Methods in Cancer Research. Vol. 1 — The Analysis of Case‐Control Studies ” pp . 192 – 246 ( 1980. ). IARC; , Lyon . [PubMed] [Google Scholar]
  • 26).Potter , J. D. , Slattery , M. L. , Bostick , R. M. and Gapstur , S. M.Colon cancer: a review of the epidemiology . Epidemiol. Rev. , 15 , 499 – 545 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 27).Kono , S.Dietary factors for gastrointestinal cancers: a worldwide overview . Gann Monogr. Cancer Res. , 44 , 29 – 39 ( 1996. ). [Google Scholar]
  • 28).Steinmetz , M. H. and Potter , J. D.Vegetables, fruits and cancer. I. Epidemiology . Cancer Causes Control , 2 , 325 – 357 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 29).Giovannucci , E. , Colditz , G. A. , Stampfer , M. J. , Hunter , D. , Rosner , B. A. , Willett , W. C. and Speizer , F. E.A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women . J. Natl. Cancer Inst. , 86 , 192 – 199 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 30).Hoshiyama , Y. , Sekine , T. and Sasaba , T.A case‐control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan . Tohoku J. Exp. Med. , 171 , 153 – 165 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 31).Wickramasinghe , S. N. , Gardner , B. and Barden , G.Cytotoxic protein molecules generated as a consequence of ethanol metabolism in vitro and in vivo . Lancet , ii , 823 – 826 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 32).Fang , J. L. and Vaca , C. E.Development of a 32P‐postla‐belling method for the analysis of adducts arising through the reaction of acetaldehyde with 2′‐deoxyguanosine‐3′‐monophosphate and DNA . Carcinogenesis , 16 , 2177 – 2185 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 33).Woutersen , R. A. , Appelman , L. M. , van , G. H. A. and Feron , V. J.Inhalation toxicity of acetaldehyde in rat. III. Carcinogenicity study . Toxicology , 41 , 212 – 231 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 34).Garro , A. J. , Espina , N. , McBeth , D. L. , Wang , S. L. and Wu Wang , C. Y.Effects of alcohol consumption on DNA methylation reactions and gene expression: implications for increased cancer risk . Eur. J. Cancer Prev. , 1 ( Suppl. 3 ), 19 – 23 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 35).Cravo , M. L. , Mason , J. B. , Dayal , Y. , Huchinson , M. , Smith , D. , Selhub , J. and Rosenberg , I. H.Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine‐treated rats . Cancer Res. , 52 , 5002 – 5006 ( 1992. ). [PubMed] [Google Scholar]
  • 36).Takeshita , T. , Kawai , T. and Morimoto , K.Elevated levels of hemoglobin‐associated acetaldehyde related to alcohol drinking in the atypical genotype of low Km aldehyde dehydrogenase . Cancer Res. , 57 , 1241 – 1243 ( 1997. ). [PubMed] [Google Scholar]
  • 37).Yokoyama , A. , Muramatsu , T. , Ohmori , T. , Yokoyama , T. , Okuyama , K. , Takahashi , H. , Hasegawa , Y. , Higuchi , S. , Maruyama , K. , Shirakura , K. and Ishii , H.Alcohol‐related cancers and aldehyde dehydrogenase‐2 in Japanese alcoholics . Carcinogenesis , 9 , 1383 – 1387 ( 1998. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES