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The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium

Ugai T 1 , Milne RL 2 , Ito H 3 , Aronson KJ 4 , Bolla MK 5 , Chan T 6 Show all authors , Chan CW 7 , Choi JY 8 , Conroy DM 9 , Dennis J 5 , Dunning AM 9 , Easton DF 5 , Gaborieau V 10 , Gonzalez-Neira A 11 , Hartman M 7 , Healey CS 9 , Iwasaki M 12 , John EM 13 , Kang D 8 , Kim SW 14 , Kwong A 6 , Lophatananon A 15 , Michailidou K 5 , Taib NAM 16 , Muir K 15 , Park SK 17 , Pharoah PDP 5 , Sangrajrang S 18 , Shen CY 19 , Shu XO 20 , Spinelli JJ 21 , Teo SH 16 , Tessier DC 22 , Tseng CC 23 , Tsugane S 12 , Vincent D 22 , Wang Q 5 , Wu AH 23 , Wu PE 19 , Zheng W 20 , Matsuo K 1

Affiliations 

  • 1 Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 2 Cancer Epidemiology & Intelligence Division, Melbourne, VIC, Australia
  • 3 Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 4 Department of Public Health Sciences, Queen's Cancer Institute, Queen's University, Kingston, Ontario, Canada
  • 5 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 6 Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong
  • 7 Department of Surgery, National University Health System, Singapore
  • 8 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
  • 9 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 10 Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
  • 11 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
  • 12 Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • 13 Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA
  • 14 Department of Surgery, Daerim Saint Mary's Hospital, Seoul, Korea
  • 15 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
  • 16 Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 17 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 18 National Cancer Institute, Bangkok, Thailand
  • 19 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  • 20 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  • 21 School of Population & Public Health, University of British Columbia, Vancouver, British Columbia, Canada
  • 22 McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada
  • 23 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Mol Genet Genomic Med, 2019 Jun;7(6):e707.
PMID: 31066241 DOI: 10.1002/mgg3.707

Abstract

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.

METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.

RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).

CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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