TY - JOUR
T1 - Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese
AU - Kanda, Junya
AU - Matsuo, Keitaro
AU - Suzuki, Takeshi
AU - Kawase, Takakazu
AU - Hiraki, Akio
AU - Watanabe, Miki
AU - Mizuno, Nobumasa
AU - Sawaki, Akira
AU - Yamao, Kenji
AU - Tajima, Kazuo
AU - Tanaka, Hideo
PY - 2009
Y1 - 2009
N2 - The putative impact of alcohol on pancreatic cancer (PC) risk remains controversial. Here, we conducted a case-control study in Japanese to assess the impact of alcohol in conjunction with polymorphisms in alcohol-metabolizing enzymes. Cases were 160 patients with pancreatic cancer at Aichi Cancer Center, Nagoya, Japan. Two control groups of 800 age- and sex-matched non-cancer subjects each were independently selected. The impact of alcohol and polymorphisms in aldehyde dehydrogenase 2 (ALDH2) Glu504Lys, alcohol dehydrogenase (ADH) 1B His48Arg, and ADH1C Arg272Gln on PC risk was examined with multivariate analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed no independent impact of alcohol or genotype on PC risk except former drinking. To avoid reverse causation, former drinkers were excluded in further analyses. In the analysis of the combined effects of alcohol consumption and genotype, significant impact of alcohol was seen for those subjects with ALDH2 Lys+ allele, ADH1B His/His, or ADH1C Arg/Arg (trend P = 0.077, 0.003, or 0.020, respectively), each of which is associated with a high concentration or rapid production of acetaldehyde. Analysis of genotype combinations showed that 'ever drinking' with both ADH1B His/His and ALDH2 Lys+ was the most potent risk factor for PC relative to 'never drinkers' with both ADH1B His/His and ALDH2 Glu/Glu [OR (95% CI); 4.09 (1.30-12.85)]. These results indicate that alcohol has an impact on PC risk when the effects of alcohol consumption and metabolism are combined. Acetaldehyde may be involved in the mechanisms underlying PC development.
AB - The putative impact of alcohol on pancreatic cancer (PC) risk remains controversial. Here, we conducted a case-control study in Japanese to assess the impact of alcohol in conjunction with polymorphisms in alcohol-metabolizing enzymes. Cases were 160 patients with pancreatic cancer at Aichi Cancer Center, Nagoya, Japan. Two control groups of 800 age- and sex-matched non-cancer subjects each were independently selected. The impact of alcohol and polymorphisms in aldehyde dehydrogenase 2 (ALDH2) Glu504Lys, alcohol dehydrogenase (ADH) 1B His48Arg, and ADH1C Arg272Gln on PC risk was examined with multivariate analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed no independent impact of alcohol or genotype on PC risk except former drinking. To avoid reverse causation, former drinkers were excluded in further analyses. In the analysis of the combined effects of alcohol consumption and genotype, significant impact of alcohol was seen for those subjects with ALDH2 Lys+ allele, ADH1B His/His, or ADH1C Arg/Arg (trend P = 0.077, 0.003, or 0.020, respectively), each of which is associated with a high concentration or rapid production of acetaldehyde. Analysis of genotype combinations showed that 'ever drinking' with both ADH1B His/His and ALDH2 Lys+ was the most potent risk factor for PC relative to 'never drinkers' with both ADH1B His/His and ALDH2 Glu/Glu [OR (95% CI); 4.09 (1.30-12.85)]. These results indicate that alcohol has an impact on PC risk when the effects of alcohol consumption and metabolism are combined. Acetaldehyde may be involved in the mechanisms underlying PC development.
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U2 - 10.1111/j.1349-7006.2008.01044.x
DO - 10.1111/j.1349-7006.2008.01044.x
M3 - Article
C2 - 19068087
AN - SCOPUS:58549084395
SN - 1347-9032
VL - 100
SP - 296
EP - 302
JO - Cancer science
JF - Cancer science
IS - 2
ER -
