title: Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer.
abstract: OBJECTIVE
  Germ-line genetic variation may affect clinical outcomes of cancer patients. We applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain interindividual differences in treatment outcomes.
  
  
  METHODS
  In total, 211 patients with pancreatic cancer were recruited in a population-based study. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous genome-wide association study data set. The main effects of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models.
  
  
  RESULTS
  Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene; rs17091162 at SERPINA3; and rs2231164 at ABCG2 had the lowest P of 10(-4.60), 0.0013, and 0.0023, respectively. We also observed that 2 genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and 2 others, TYMS and MET, showed evidence of interaction with 5-fluorouracil and erlotinib, respectively.
  
  
  CONCLUSIONS
  Our study suggested significant associations between germ-line genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy.
authors.affiliation: Department of Epidemiology and Public Health, School of Public Health and School of Medicine, Yale University, New Haven, CT 06520-8034, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zeng
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Jain
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kidd
authors.forename: M Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003237:Connecticut / Q000453:epidemiology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D015843:Serpins / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D005819:Genetic Markers; D009363:Neoplasm Proteins; C516148:SERPINA3 protein, human; D015843:Serpins; D042943:Dihydrouracil Dehydrogenase (NADP)