Gastric Cancer

, Volume 21, Issue 6, pp 936–945 | Cite as

Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis

  • Kuka Ishioka
  • Hiroyuki Masaoka
  • Hidemi Ito
  • Isao Oze
  • Seiji Ito
  • Masahiro Tajika
  • Yasuhiro Shimizu
  • Yasumasa Niwa
  • Shigeo Nakamura
  • Keitaro MatsuoEmail author
Original Article



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.


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.


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 (Pinteraction = 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.


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.


Alcohol drinking ALDH2 ADH1B Gastric cancer Interaction Mediation analysis 



We appreciate all the participants who have contributed to the HERPACC studies. This study was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, consisting of Priority Areas of Cancer (no. 17015018), Innovative Areas (no. 221S0001), JSPS KAKENHI Grant (nos. 16H06277, 15K08792, 26860430, 17K15841, 26253041) and by a Grant-in-Aid for the Third Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan and the Health, and Cancer Bio Bank Aichi.

Compliance with ethical standards

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Informed consent

Informed consent to be included in the study, or the equivalent, was obtained from all patients.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10120_2018_823_MOESM1_ESM.pdf (53 kb)
Supplementary material 1 (PDF 52 kb)
10120_2018_823_MOESM2_ESM.pdf (49 kb)
Supplementary material 2 (PDF 48 kb)
10120_2018_823_MOESM3_ESM.pdf (43 kb)
Supplementary material 3 (PDF 42 kb)
10120_2018_823_MOESM4_ESM.pdf (46 kb)
Supplementary material 4 (PDF 45 kb)
10120_2018_823_MOESM5_ESM.pdf (47 kb)
Supplementary material 5 (PDF 47 kb)


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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  1. 1.Department of Pathology and Clinical LaboratoriesNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Division of Molecular and Clinical EpidemiologyAichi Cancer Center Research InstituteNagoyaJapan
  3. 3.Department of Urology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of EpidemiologyNagoya University Graduate School of MedicineNagoyaJapan
  5. 5.Department of Gastroenterological SurgeryAichi Cancer Center HospitalNagoyaJapan
  6. 6.Department of GastroenterologyAichi Cancer Center HospitalNagoyaJapan

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