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.
authors.affiliation: Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Er-Chieh
authors.initials: EC
authors.lastname: Cho
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.|Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.affiliation: Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.|Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Hung
authors.affiliation: Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Mao-Chih
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.|Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Tien
authors.initials: CT
authors.lastname: Su
authors.affiliation: Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Hwa
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan. hychiou@tmu.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein