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

Tomotaka Ugai, Roger L Milne, Hidemi Ito, Kristan J Aronson, Manjeet K Bolla, Tsun Chan, Ching W Chan, Ji-Yeob Choi, Don M Conroy, Joe Dennis, Alison M Dunning, Douglas F Easton, Valerie Gaborieau, Anna Gonzalez-Neira, Mikael Hartman, Catherine S Healey, Motoki Iwasaki, Esther M John, Daehee Kang, Sung-Won KimAva Kwong, Artitaya Lophatananon, Kyriaki Michailidou, Nur Aishah Mohd Taib, Kenneth Muir, Sue K Park, Paul D P Pharoah, Suleeporn Sangrajrang, Chen-Yang Shen, Xiao-Ou Shu, John J Spinelli, Soo H Teo, Daniel C Tessier, Chiu-Chen Tseng, Shoichiro Tsugane, Daniel Vincent, Qin Wang, Anna H Wu, Pei-Ei Wu, Wei Zheng, Keitaro Matsuo

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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.

Original languageEnglish
Pages (from-to)e707
JournalMolecular Genetics and Genomic Medicine
Volume7
Issue number6
DOIs
Publication statusPublished - 13 Jun 2019

Keywords

  • Adult
  • Aged
  • Alcohol Drinking/epidemiology
  • Aldehyde Dehydrogenase, Mitochondrial/genetics
  • Asian Continental Ancestry Group/genetics
  • Breast Neoplasms/epidemiology
  • Female
  • Gene-Environment Interaction
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide

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