title: Common variants in genes coding for chemotherapy metabolizing enzymes, transporters, and targets: a case-control study of contralateral breast cancer risk in the WECARE Study.
abstract: OBJECTIVE
  Women who receive chemotherapy for a first primary breast cancer have been observed to have a reduced risk of contralateral breast cancer (CBC), however, whether the genetic profile of a patient modifies this protective effect is currently not understood. The purpose of this study is to investigate the impact of germline genetic variation in genes coding for drug metabolizing enzymes, transporters, and targets on the association between chemotherapy and risk of CBC.
  
  
  METHODS
  From the population-based Women's Environment Cancer and Radiation Epidemiology (WECARE) Study, we included 636 Caucasian women with CBC (cases) and 1,224 women with unilateral breast cancer (controls). The association between common chemotherapeutic regimens, CMF and FAC/FEC, and risk of CBC stratified by genotype of 180 single nucleotide polymorphisms in 14 genes selected for their known involvement in metabolism, action, and transport of breast cancer chemotherapeutic agents, were determined using conditional logistic regression.
  
  
  RESULTS
  CMF (RR = 0.5, 95 % CI 0.4, 0.7) and FAC/FEC (RR = 0.7, 95 % CI 0.4, 1.0) are associated with lower CBC risk relative to no chemotherapy in multivariable-adjusted models. Here we show that genotype of selected genes involved in the metabolism and uptake of these therapeutic agents does not significantly alter the protective effect of either CMF or FAC/FEC on risk of CBC.
  
  
  CONCLUSIONS
  The results of this study show that germline genetic variation in selected gene does not significantly alter the protective effect of CMF, FAC, and FEC on risk of CBC.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 E 63rd Street, 3rd Floor, New York, NY, USA. brooksj@mskcc.org
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Teraoka
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjær
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: David J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: Katherine
authors.initials: K
authors.lastname: Schiermeyer
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D008875:Middle Aged; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012042:Registries; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D026901:Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System; D008780:Methyltransferases