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

Research output: Contribution to journalArticle

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
Article numbere707
JournalMolecular Genetics and Genomic Medicine
Volume7
Issue number6
DOIs
StatePublished - Jun 2019

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Keywords

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

Cite this

Ugai, T., Milne, R. L., Ito, H., Aronson, K. J., Bolla, M. K., Chan, T., Chan, C. W., Choi, J. Y., Conroy, D. M., Dennis, J., Dunning, A. M., Easton, D. F., Gaborieau, V., Gonzalez-Neira, A., Hartman, M., Healey, C. S., Iwasaki, M., John, E. M., Kang, D., ... Matsuo, K. (2019). The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium. Molecular Genetics and Genomic Medicine, 7(6), [e707]. https://doi.org/10.1002/mgg3.707