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 Kim; Ava 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

doi:10.1002/mgg3.707

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

Division of Population Health, Health Services Research & Primary Care (L5)

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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 language	English
Pages (from-to)	e707
Journal	Molecular Genetics and Genomic Medicine
Volume	7
Issue number	6
DOIs	https://doi.org/10.1002/mgg3.707
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

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

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 = "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",

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

note = "{\textcopyright} 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",

year = "2019",

month = jun,

day = "13",

doi = "10.1002/mgg3.707",

language = "English",

volume = "7",

pages = "e707",

journal = "Molecular Genetics and Genomic Medicine",

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Ugai, T, Milne, RL, Ito, H, Aronson, KJ, Bolla, MK, Chan, T, Chan, CW, Choi, J-Y, Conroy, DM, Dennis, J, Dunning, AM, Easton, DF, Gaborieau, V, Gonzalez-Neira, A, Hartman, M, Healey, CS, Iwasaki, M, John, EM, Kang, D, Kim, S-W, Kwong, A, Lophatananon, A, Michailidou, K, Taib, NAM, Muir, K, Park, SK, Pharoah, PDP, Sangrajrang, S, Shen, C-Y, Shu, X-O, Spinelli, JJ, Teo, SH, Tessier, DC, Tseng, C-C, Tsugane, S, Vincent, D, Wang, Q, Wu, AH, Wu, P-E, Zheng, W & 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, vol. 7, no. 6, pp. e707. https://doi.org/10.1002/mgg3.707

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

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

VL - 7

SP - e707

JO - Molecular Genetics and Genomic Medicine

JF - Molecular Genetics and Genomic Medicine

SN - 2324-9269

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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