BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.
BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.
Authors: Eva Krauss; Stephan Rauthe; Stefan Gattenlöhner; Tobias Reuther; Michael Kochel; Ulrike Kriegebaum; Alexander C Kübler; Urs D A Müller-Richter Journal: Clin Oral Investig Date: 2010-02-20 Impact factor: 3.573
Authors: Mark P Purdue; Mia Hashibe; Julien Berthiller; Carlo La Vecchia; Luigino Dal Maso; Rolando Herrero; Silvia Franceschi; Xavier Castellsague; Qingyi Wei; Erich M Sturgis; Hal Morgenstern; Zuo-Feng Zhang; Fabio Levi; Renato Talamini; Elaine Smith; Joshua Muscat; Philip Lazarus; Stephen M Schwartz; Chu Chen; Jose Eluf Neto; Victor Wünsch-Filho; David Zaridze; Sergio Koifman; Maria Paula Curado; Simone Benhamou; Elena Matos; Neonilia Szeszenia-Dabrowska; Andrew F Olshan; Juan Lence; Ana Menezes; Alexander W Daudt; Ioan Nicolae Mates; Agnieszka Pilarska; Eleonora Fabianova; Peter Rudnai; Debbie Winn; Gilles Ferro; Paul Brennan; Paolo Boffetta; Richard B Hayes Journal: Am J Epidemiol Date: 2008-12-08 Impact factor: 4.897
Authors: Gioia Di Credico; Valeria Edefonti; Jerry Polesel; Francesco Pauli; Nicola Torelli; Diego Serraino; Eva Negri; Daniele Luce; Isabelle Stucker; Keitaro Matsuo; Paul Brennan; Marta Vilensky; Leticia Fernandez; Maria Paula Curado; Ana Menezes; Alexander W Daudt; Rosalina Koifman; Victor Wunsch-Filho; Ivana Holcatova; Wolfgang Ahrens; Pagona Lagiou; Lorenzo Simonato; Lorenzo Richiardi; Claire Healy; Kristina Kjaerheim; David I Conway; Tatiana V Macfarlane; Peter Thomson; Antonio Agudo; Ariana Znaor; Leonardo F Boaventura Rios; Tatiana N Toporcov; Silvia Franceschi; Rolando Herrero; Joshua Muscat; Andrew F Olshan; Jose P Zevallos; Carlo La Vecchia; Deborah M Winn; Erich M Sturgis; Guojun Li; Eleonora Fabianova; Jolanda Lissowska; Dana Mates; Peter Rudnai; Oxana Shangina; Beata Swiatkowska; Kirsten Moysich; Zuo-Feng Zhang; Hal Morgenstern; Fabio Levi; Elaine Smith; Philip Lazarus; Cristina Bosetti; Werner Garavello; Karl Kelsey; Michael McClean; Heribert Ramroth; Chu Chen; Stephen M Schwartz; Thomas L Vaughan; Tongzhang Zheng; Gwenn Menvielle; Stefania Boccia; Gabriella Cadoni; Richard B Hayes; Mark Purdue; Maura Gillison; Stimson Schantz; Guo-Pei Yu; Hermann Brenner; Gypsyamber D'Souza; Neil D Gross; Shu-Chun Chuang; Paolo Boffetta; Mia Hashibe; Yuan-Chin Amy Lee; Luigino Dal Maso Journal: Oral Oncol Date: 2019-05-17 Impact factor: 5.337
Authors: Anne M Hakenewerth; Robert C Millikan; Ivan Rusyn; Amy H Herring; Kari E North; Jill S Barnholtz-Sloan; William F Funkhouser; Mark C Weissler; Andrew F Olshan Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-09-22 Impact factor: 4.254
Authors: Eva Negri; Paolo Boffetta; Julien Berthiller; Xavier Castellsague; Maria Paula Curado; Luigino Dal Maso; Alexander W Daudt; Eleonora Fabianova; Leticia Fernandez; Victor Wünsch-Filho; Silvia Franceschi; Richard B Hayes; Rolando Herrero; Sergio Koifman; Philip Lazarus; Juan J Lence; Fabio Levi; Dana Mates; Elena Matos; Ana Menezes; Joshua Muscat; Jose Eluf-Neto; Andrew F Olshan; Peter Rudnai; Oxana Shangina; Erich M Sturgis; Neonilia Szeszenia-Dabrowska; Renato Talamini; Qingyi Wei; Deborah M Winn; David Zaridze; Jolanta Lissowska; Zuo-Feng Zhang; Gilles Ferro; Paul Brennan; Carlo La Vecchia; Mia Hashibe Journal: Int J Cancer Date: 2009-01-15 Impact factor: 7.396