Open AccessThe functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium
Author(s) -
Ugai Tomotaka,
Milne Roger L.,
Ito Hidemi,
Aronson Kristan J.,
Bolla Manjeet K.,
Chan Tsun,
Chan Ching W.,
Choi JiYeob,
Conroy Don M.,
Dennis Joe,
Dunning Alison M.,
Easton Douglas F.,
Gaborieau Valerie,
GonzalezNeira Anna,
Hartman Mikael,
Healey Catherine S.,
Iwasaki Motoki,
John Esther M.,
Kang Daehee,
Kim SungWon,
Kwong Ava,
Lophatana Artitaya,
Michailidou Kyriaki,
Taib Nur Aishah Mohd,
Muir Kenneth,
Park Sue K.,
Pharoah Paul D. P.,
Sangrajrang Suleeporn,
Shen ChenYang,
Shu XiaoOu,
Spinelli John J.,
Teo Soo H.,
Tessier Daniel C.,
Tseng ChiuChen,
Tsugane Shoichiro,
Vincent Daniel,
Wang Qin,
Wu Anna H.,
Wu PeiEi,
Zheng Wei,
Matsuo Keitaro
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.707
Subject(s) - aldh2 , odds ratio , breast cancer , medicine , confidence interval , case control study , genotype , estrogen receptor , oncology , cancer , genetics , biology , gene
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.