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Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018-11, Vol.21 (6), p.936-945
Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis
Ist Teil von
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018-11, Vol.21 (6), p.936-945
Ort / Verlag
Tokyo: Springer Japan
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Background
Aldehyde dehydrogenase 2 (
ALDH2
; rs671, Glu504Lys) and alcohol dehydrogenase 1B (
ADH1B
; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant
ALDH2
–alcohol drinking interaction and a mediation effect of
ALDH2
/
ADH1B
through alcohol drinking on gastric cancer have remained unclear. We conducted two case–control studies to validate the interaction and to estimate the mediation effect on gastric cancer.
Methods
We calculated odds ratios (OR) and 95% confidence intervals (CI) for
ALDH2
/
ADH1B
genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways.
Results
ALDH2
Lys alleles had a higher risk with increased alcohol consumption compared with
ALDH2
Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04–6.27;
P
for trend = 0.007), indicating a significant
ALDH2
–alcohol drinking interaction (
P
interaction
= 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38–2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76–0.92) of the
ALDH2
Lys alleles with the
ALDH2
–alcohol drinking interaction. No significant association of
ADH1B
with gastric cancer was observed.
Conclusion
The observed
ALDH2
–alcohol drinking interaction and the direct effect of
ALDH2
Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.