TY - JOUR
T1 - The functional ALDH2 polymorphism is associated with breast cancer risk
T2 - A pooled analysis from the Breast Cancer Association Consortium
AU - Ugai, Tomotaka
AU - Milne, Roger L
AU - Ito, Hidemi
AU - Aronson, Kristan J
AU - Bolla, Manjeet K
AU - Chan, Tsun
AU - Chan, Ching W
AU - Choi, Ji-Yeob
AU - Conroy, Don M
AU - Dennis, Joe
AU - Dunning, Alison M
AU - Easton, Douglas F
AU - Gaborieau, Valerie
AU - Gonzalez-Neira, Anna
AU - Hartman, Mikael
AU - Healey, Catherine S
AU - Iwasaki, Motoki
AU - John, Esther M
AU - Kang, Daehee
AU - Kim, Sung-Won
AU - Kwong, Ava
AU - Lophatananon, Artitaya
AU - Michailidou, Kyriaki
AU - Taib, Nur Aishah Mohd
AU - Muir, Kenneth
AU - Park, Sue K
AU - Pharoah, Paul D P
AU - Sangrajrang, Suleeporn
AU - Shen, Chen-Yang
AU - Shu, Xiao-Ou
AU - Spinelli, John J
AU - Teo, Soo H
AU - Tessier, Daniel C
AU - Tseng, Chiu-Chen
AU - Tsugane, Shoichiro
AU - Vincent, Daniel
AU - Wang, Qin
AU - Wu, Anna H
AU - Wu, Pei-Ei
AU - Zheng, Wei
AU - Matsuo, Keitaro
N1 - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
PY - 2019/6/13
Y1 - 2019/6/13
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Alcohol Drinking/epidemiology
KW - Aldehyde Dehydrogenase, Mitochondrial/genetics
KW - Asian Continental Ancestry Group/genetics
KW - Breast Neoplasms/epidemiology
KW - Female
KW - Gene-Environment Interaction
KW - Humans
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
U2 - 10.1002/mgg3.707
DO - 10.1002/mgg3.707
M3 - Article
C2 - 31066241
SN - 2324-9269
VL - 7
SP - e707
JO - Molecular Genetics and Genomic Medicine
JF - Molecular Genetics and Genomic Medicine
IS - 6
ER -