Document Detail

Recommendations and proposed guidelines for assessing the cumulative evidence on joint effects of genes and environments on cancer occurrence in humans.
MedLine Citation:
PMID:  22596931     Owner:  NLM     Status:  MEDLINE    
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.
Paolo Boffetta; Deborah M Winn; John P Ioannidis; Duncan C Thomas; Julian Little; George Davey Smith; Vincent J Cogliano; Stephen S Hecht; Daniela Seminara; Paolo Vineis; Muin J Khoury
Publication Detail:
Type:  Journal Article     Date:  2012-05-16
Journal Detail:
Title:  International journal of epidemiology     Volume:  41     ISSN:  1464-3685     ISO Abbreviation:  Int J Epidemiol     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-12-04     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7802871     Medline TA:  Int J Epidemiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  686-704     Citation Subset:  IM    
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MeSH Terms
Arylamine N-Acetyltransferase / genetics
Data Interpretation, Statistical
Gene-Environment Interaction*
Models, Theoretical
Neoplasms / epidemiology,  genetics*
Practice Guidelines as Topic*
Research Design*
Smoking / genetics
Urinary Bladder Neoplasms / genetics
Grant Support
G0600705//Medical Research Council
Reg. No./Substance:
EC N-Acetyltransferase; EC protein, human
Comment In:
Int J Epidemiol. 2012 Jun;41(3):707-10   [PMID:  22596933 ]
Int J Epidemiol. 2012 Jun;41(3):705-7   [PMID:  22596932 ]

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