title: Recommendations and proposed guidelines for assessing the cumulative evidence on joint effects of genes and environments on cancer occurrence in humans.
abstract: We propose guidelines to evaluate the cumulative evidence of gene-environment (G × E) interactions in the causation of human cancer. Our approach has its roots in the HuGENet and IARC Monographs evaluation processes for genetic and environmental risk factors, respectively, and can be applied to common chronic diseases other than cancer. We first review issues of definitions of G × E interactions, discovery and modelling methods for G × E interactions, and issues in systematic reviews of evidence for G × E interactions, since these form the foundation for appraising the credibility of evidence in this contentious field. We then propose guidelines that include four steps: (i) score the strength of the evidence for main effects of the (a) environmental exposure and (b) genetic variant; (ii) establish a prior score category and decide on the pattern of interaction to be expected; (iii) score the strength of the evidence for interaction between the environmental exposure and the genetic variant; and (iv) examine the overall plausibility of interaction by combining the prior score and the strength of the evidence and interpret results. We finally apply the scheme to the interaction between NAT2 polymorphism and tobacco smoking in determining bladder cancer risk.
authors.affiliation: Tisch Cancer Institute, Mount Sinai School of Medicine, NY, USA. paolo.boffetta@mssm.edu
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Winn
authors.forename: John P
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Cogliano
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Muin J
authors.initials: MJ
authors.lastname: Khoury
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D003627:Data Interpretation, Statistical; D059647:Gene-Environment Interaction; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017410:Practice Guidelines as Topic; D012107:Research Design; D012907:Smoking / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human