TY - JOUR
T1 - Modification of occupational exposures on bladder cancer risk by common genetic polymorphisms
AU - Figueroa, Jonine D.
AU - Koutros, Stella
AU - Colt, Joanne S.
AU - Kogevinas, Manolis
AU - Garcia-Closas, Montserrat
AU - Real, Francisco X.
AU - Friesen, Melissa C.
AU - Baris, Dalsu
AU - Stewart, Patricia
AU - Schwenn, Molly
AU - Johnson, Alison
AU - Karagas, Margaret R.
AU - Armenti, Karla R.
AU - Moore, Lee E.
AU - Schned, Alan
AU - Lenz, Petra
AU - Prokunina-Olsson, Ludmila
AU - Banday, A. Rouf
AU - Paquin, Ashley
AU - Ylaya, Kris
AU - Chung, Joon Yong
AU - Hewitt, Stephen M.
AU - Nickerson, Michael L.
AU - Tardón, Adonina
AU - Serra, Consol
AU - Carrato, Alfredo
AU - García-Closas, Reina
AU - Lloreta, Josep
AU - Malats, Núria
AU - Fraumeni, Joseph F.
AU - Chanock, Stephen J.
AU - Chatterjee, Nilanjan
AU - Rothman, Nathaniel
AU - Silverman, Debra T.
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press. All rights reserved.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/djv223
DO - 10.1093/jnci/djv223
M3 - Article
C2 - 26374428
AN - SCOPUS:84946203061
SN - 0027-8874
VL - 107
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 11
ER -