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Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Ferrari, P.; McKay, J. D.; Jenab, M.; Brennan, P.; Canzian, F.; Vogel, U.; Tjonneland, A.; Overvad, K.; Tolstrup, J. S. and Boutron-Ruault, M-C, et al. (2012) In European Journal of Clinical Nutrition 66(12). p.1303-1308
Abstract
BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations. SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated... (More)
BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations. SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors. RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07). CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 2012 (Less)
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keywords
acetaldehyde, aldehyde dehydrogenase, polymorphism, alcohol intake, colorectal cancer
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European Journal of Clinical Nutrition
volume
66
issue
12
pages
1303 - 1308
publisher
Nature Publishing Group
external identifiers
  • wos:000312083600005
  • scopus:84870769156
ISSN
1476-5640
DOI
10.1038/ejcn.2012.173
language
English
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yes
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01d9c5b7-1e40-4ebf-9258-6769f39c0b13 (old id 3367949)
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2013-02-01 06:58:27
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@article{01d9c5b7-1e40-4ebf-9258-6769f39c0b13,
  abstract     = {BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations. SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors. RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff&lt;0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07). CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 2012},
  author       = {Ferrari, P. and McKay, J. D. and Jenab, M. and Brennan, P. and Canzian, F. and Vogel, U. and Tjonneland, A. and Overvad, K. and Tolstrup, J. S. and Boutron-Ruault, M-C and Clavel-Chapelon, F. and Morois, S. and Kaaks, R. and Boeing, H. and Bergmann, M. and Trichopoulou, A. and Katsoulis, M. and Trichopoulos, D. and Krogh, V. and Panico, S. and Sacerdote, C. and Palli, D. and Tumino, R. and Peeters, P. H. and van Gils, C. H. and Bueno-de-Mesquita, B. and Vrieling, A. and Lund, E. and Hjartaker, A. and Agudo, A. and Suarez, L. R. and Arriola, L. and Chirlaque, M-D and Ardanaz, E. and Sanchez, M-J and Manjer, Jonas and Lindkvist, B. and Hallmans, G. and Palmqvist, R. and Allen, N. and Key, T. and Khaw, K-T and Slimani, N. and Rinaldi, S. and Romieu, I. and Boffetta, P. and Romaguera, D. and Norat, T. and Riboli, E.},
  issn         = {1476-5640},
  keyword      = {acetaldehyde,aldehyde dehydrogenase,polymorphism,alcohol intake,colorectal cancer},
  language     = {eng},
  number       = {12},
  pages        = {1303--1308},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Clinical Nutrition},
  title        = {Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study},
  url          = {http://dx.doi.org/10.1038/ejcn.2012.173},
  volume       = {66},
  year         = {2012},
}