Abstract

Background: Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. Methods: This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2.Results: Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. Conclusions: A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalAnnals of Surgical Oncology
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

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Taiwan
Breast Neoplasms
DNA Mismatch Repair
Single Nucleotide Polymorphism
Luciferases
Genotype
Genes
Logistic Models
Odds Ratio
Regression Analysis
Confidence Intervals
Cell Line
Incidence

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

@article{6a0dee318df34008bafa87a959962236,
title = "MSH2 rs2303425 Polymorphism is Associated with Early-Onset Breast Cancer in Taiwan",
abstract = "Background: Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. Methods: This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2.Results: Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 {\%} confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. Conclusions: A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.",
author = "Hsieh, {Yi Chen} and Cho, {Er Chieh} and Tu, {Shih Hsin} and Wu, {Chih Hsiung} and Hung, {Chin Sheng} and Mao-Chih Hsieh and Su, {Chien Tien} and Yun-Ru Liu and Lee, {Chia Hwa} and Ho, {Yuan Soon} and Chiou, {Hung Yi}",
year = "2017",
month = "2",
day = "1",
doi = "10.1245/s10434-016-5168-5",
language = "English",
volume = "24",
pages = "603--610",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - MSH2 rs2303425 Polymorphism is Associated with Early-Onset Breast Cancer in Taiwan

AU - Hsieh, Yi Chen

AU - Cho, Er Chieh

AU - Tu, Shih Hsin

AU - Wu, Chih Hsiung

AU - Hung, Chin Sheng

AU - Hsieh, Mao-Chih

AU - Su, Chien Tien

AU - Liu, Yun-Ru

AU - Lee, Chia Hwa

AU - Ho, Yuan Soon

AU - Chiou, Hung Yi

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background: Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. Methods: This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2.Results: Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. Conclusions: A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

AB - Background: Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. Methods: This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2.Results: Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. Conclusions: A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

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JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

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