title: Candidate gene-environment interactions in breast cancer.
abstract: Gene-environment interactions have the potential to shed light on biological processes leading to disease, identify individuals for whom risk factors are most relevant, and improve the accuracy of epidemiological risk models. We review the progress that has been made in investigating gene-environment interactions in the field of breast cancer. Although several large-scale analyses have been carried out, only a few significant interactions have been reported. One of these, an interaction between CASP8-rs1045485 and alcohol consumption has been replicated, but others have not, including LSP1- rs3817198 and parity, and 1p11.2-rs11249433 and ever being parous. False positive interactions may arise if the gene and environment are correlated and the causal variant is less frequent than the tag SNP. We conclude that while much progress has been made in this area it is still too soon to tell whether gene-environment interactions will fulfil their promise. Before we can make this assessment we will need to replicate (or refute) the reported interactions, identify the causal variants that underlie tag-SNP associations and validate the next generation of epidemiological risk models.
authors.affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK. Olivia.Fletcher@icr.ac.uk.|Division of Breast Cancer Research, The Institute of Cancer Research, London, SW3 6JB, UK. Olivia.Fletcher@icr.ac.uk.
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
authors.affiliation: Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. Frank.Dudbridge@lshtm.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors