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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\u2010set 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\u2013control 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 (<jats:italic>p<\/jats:italic> = 0.008). This association was mainly driven by genetic variation in <jats:italic>NAT2, CYP2C18, CYP2C19, AKR1C2<\/jats:italic> and <jats:italic>ALDH1A3<\/jats:italic>. The association between the XM gene pathway and breast cancer was observed among current and previous smokers, but not among never smokers (<jats:italic>p<\/jats:italic> = 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.<\/jats:p>","DOI":"10.1002\/ijc.31917","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T16:41:42Z","timestamp":1539189702000},"page":"1896-1908","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Association of breast cancer risk with polymorphisms in genes involved in the metabolism of xenobiotics and interaction with tobacco smoking: A gene\u2010set analysis"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-3002","authenticated-orcid":false,"given":"Takiy","family":"Berrandou","sequence":"first","affiliation":[{"name":"INSERM, Center for Research in Epidemiology and Population Health (CESP) Cancer and Environment 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