Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms

Jonine D Figueroa, Stella Koutros, Joanne S Colt, Manolis Kogevinas, Montserrat Garcia-Closas, Francisco X Real, Melissa C Friesen, Dalsu Baris, Patricia Stewart, Molly Schwenn, Alison Johnson, Margaret R Karagas, Karla R Armenti, Lee E Moore, Alan Schned, Petra Lenz, Ludmila Prokunina-Olsson, A Rouf Banday, Ashley Paquin, Kris YlayaJoon-Yong Chung, Stephen M Hewitt, Michael L Nickerson, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Núria Malats, Joseph F Fraumeni Jr, Stephen J Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Debra T Silverman

Research output: Contribution to journalArticlepeer-review

Abstract

Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (Pinteraction ≤ .001), rs11892031 (UGT1A, Pinteraction = .01), and rs798766 (TMEM129-TACC3-FGFR3, Pinteraction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, Pinteraction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis.
Original languageEnglish
Article numberdjv223
Number of pages5
JournalJNCI: Journal of the National Cancer Institute
Volume107
Issue number11
Early online date14 Sep 2015
DOIs
Publication statusPublished - Nov 2015

Keywords

  • Adult
  • Aged
  • Female
  • Gene Deletion
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Glucuronosyltransferase
  • Glutathione Transferase
  • Humans
  • Male
  • Metallurgy
  • Microtubule-Associated Proteins
  • Middle Aged
  • Occupational Diseases
  • Occupational Exposure
  • Polymorphism, Single Nucleotide
  • Receptor, Fibroblast Growth Factor, Type 3
  • Risk Factors
  • Scotland
  • Surveys and Questionnaires
  • Ubiquitin-Protein Ligases
  • Urinary Bladder Neoplasms

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