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Association of breast cancer risk with polymorphisms in genes involved in the metabolism of xenobiotics and interaction with tobacco smoking: A gene‐set analysis
Author(s) -
Berrandou Takiy,
Mulot Claire,
CordinaDuverger Emilie,
Arveux Patrick,
LaurentPuig Pierre,
Truong Thérèse,
Guénel Pascal
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31917
Subject(s) - single nucleotide polymorphism , breast cancer , snp , gene , genetics , genotyping , tobacco smoke , genetic association , genetic variation , case control study , biology , cancer , carcinogenesis , medicine , snp genotyping , oncology , bioinformatics , genotype , environmental health
Single nucleotide polymorphisms (SNPs) in genes involved in xenobiotics metabolism (XM) are suspected to play a role in breast cancer risk. However, previous findings based on a SNP by SNP approach need to be replicated taking into account the combined effects of multiple SNPs. We used a gene‐set analysis method to study the association between breast cancer risk and genetic variation in XM genes (seen as a set of SNPs) and in the XM pathway (seen as a set of genes). We also studied the interaction between variants in XM genes and tobacco smoking. The analysis was conducted in a case–control study of 1,125 cases and 1,172 controls. Using a dedicated chip, genotyping data of 585 SNPs in 68 XM genes were available. Genetic variation in the whole XM pathway was significantly associated with premenopausal breast cancer risk ( p = 0.008). This association was mainly driven by genetic variation in NAT2, CYP2C18, CYP2C19, AKR1C2 and ALDH1A3 . The association between the XM gene pathway and breast cancer was observed among current and previous smokers, but not among never smokers ( p = 0.013 for interaction between XM genes and tobacco smoking status). The association with breast cancer risk indicates that XM genes variants may play a role in breast carcinogenesis through their detoxification function of environmental pollutants, such as those contained in tobacco smoke.