title: Association of XPC polymorphisms with susceptibility and clinical outcome to chemotherapy in breast cancer patients.
abstract: The aim of the current study was to evaluate the relation between xeroderma pigmentosum complementation group C (XPC) polymorphisms and susceptibility to breast cancer (BC), the development and progression of disease, and response to different individualized drug treatments. We investigated two polymorphisms in XPC Ala499Val and Lys939Gln using PCR-RFLP assays including 618 cases and 622 controls. The frequency of the TT genotype of Ala499Val (adjusted odds ratio = 1.575; 95% confidence interval, 1.104-2.245; P = 0.012) and the AC genotype of Lys939Gln (adjusted odds ratio = 1.330; 95% confidence interval, 1.045-1.694; P = 0.020) were found to significantly increase the risk of developing BC. The CT+TT genotypes of Ala499Val were associated with estrogen receptor positive, and Her-2 and p53 negative status, and the AC+CC genotypes of Lys939Gln were associated with BRCA1 negative status. Moreover, a significantly increased chance of treatment with neoadjuvant anthracycline-based chemotherapy response was found in women carrying TT genotype of Ala499Val, or CC and AC genotypes of Lys939Gln. In addition, a significantly longer overall survival after chemotherapy was observed in patients who had XPC Lys939Gln AC+CC genotypes with estrogen receptor positive (log-rank test, P = 0.086) and p53 negative (log-rank test, P = 0.020). The current data suggested that XPC Ala499Val and Lys939Gln polymorphisms may contribute to the identification of patients with increased risk for BC. Moreover, the polymorphisms were associated with the prognosis of BC patients.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yang
authors.forename: Duo
authors.initials: D
authors.lastname: Liu
authors.forename: Huizhe
authors.initials: H
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.forename: Hao
authors.initials: H
authors.lastname: Pang
authors.forename: Desheng
authors.initials: D
authors.lastname: Huang
authors.forename: Xianzheng
authors.initials: X
authors.lastname: Sha
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C086984:XPC protein, human