title: Contribution of DNA Double-strand Break Repair Gene XRCC3 Genotypes to Triple-negative Breast Cancer Risk.
abstract: OBJECTIVE
  The DNA-repair gene X-ray repair cross-complementing group 3 (XRCC3) is important in DNA double-strand break repair and plays a critical part in initiation of carcinogenesis. Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype with no existing gene-targeting drugs and little knowledge on its genetic etiology. This study aimed to investigate the contribution of the XRCC3 genotype to individual TNBC susceptibility.
  
  
  METHODS
  A total of 2,464 Taiwan citizens consisting of 1,232 breast cancer cases and 1,232 controls were enrolled in this case-control study, and genotyping of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539 and rs28903081 were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We also conducted risk-stratified sub-group analyses to determine the association between the genotype and age- and hormone-related characteristics of breast cancer sub-groups.
  
  
  RESULTS
  There was no significant difference between breast cancer and control groups in the distributions of the genotypic or allelic frequencies as for the XRCC3 rs1799794 (p=0.5195 and 0.9545), rs45603942 (p=0.3478 and 0.1449), rs861530 (p=0.4567 and 0.5081), rs3212057 (p=1.0000 and 1.0000), rs1799796 (p=0.8487 and 0.7315) and rs28903081 (p=1.0000 and 1.0000), respectively. However, the XRCC3 rs861539 TT genotype was more prevalent in patients with breast cancer [odds ratio (OR)=2.99, 95% confidence interval (CI)=1.62-5.55; p=0.0002], and especially among those who were younger than 55 years (OR=2.61, 95% CI=1.82-3.73; p=0.0001), with first menarche earlier than 12.2 years (OR=2.47, 95% CI=1.74-3.52; p=0.0001), with menopause at 49.0 years old or later (OR=2.53, 95% CI=1.76-3.62; p=0.0001), or with TNBC (OR=2.05, 95% CI=1.46-4.28; p=4.63*10(-4)).
  
  
  CONCLUSIONS
  XRCC3 rs861539 TT is a potential predictive marker for TNBC in Taiwanese women and investigations in other populations are warranted for further universal application in cancer detection and prediction.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Su
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
authors.forename: Pei-Shin
authors.initials: PS
authors.lastname: Hu
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chieh-Lun
authors.initials: CL
authors.lastname: Hsiao
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Hong-Xue
authors.initials: HX
authors.lastname: Ji
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C. National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Cheng-Hsi
authors.initials: CH
authors.lastname: Liao
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C. National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Yueh
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C. National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Chin-Liang
authors.initials: CL
authors.lastname: Chuang
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chin-Mu
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C. datian@mail.cmuh.org.tw artbau2@gmail.com.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008572:Menarche; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3
keywords: Genotype; XRCC3; menarche; menopause; triple-negative breast cancer