Format

Send to

Choose Destination
Mol Genet Genomic Med. 2019 Jun;7(6):e707. doi: 10.1002/mgg3.707. Epub 2019 May 7.

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

Author information

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
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
4
Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
5
Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
6
Department of Public Health Sciences, Queen's Cancer Institute, Queen's University, Kingston, Ontario, Canada.
7
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
8
Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong.
9
Department of Pathology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong.
10
Department of Surgery, National University Health System, Singapore.
11
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
12
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
13
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
14
Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
15
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.
16
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
17
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
18
Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.
19
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
20
Department of Surgery, Daerim Saint Mary's Hospital, Seoul, Korea.
21
Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Happy Valley, Hong Kong.
22
Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong.
23
Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
24
Division of Population Sciences, Warwick Medical School, Warwick University, Coventry, UK.
25
Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
26
Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
27
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
28
National Cancer Institute, Bangkok, Thailand.
29
Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
30
College of Public Health, China Medical University, Taichong, Taiwan.
31
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
32
School of Population & Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
33
Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada.
34
Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.
35
McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
36
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

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.

KEYWORDS:

acetaldehyde; alcohol drinking; aldehyde dehydrogenase-2; breast cancer; single nucleotide polymorphism

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center