Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study

Rudolph A, Hein R, Lindstrom S, Beckmann L, Behrens S, Liu J, Aschard H, Bolla MK, Wang J, Truong T, Cordina-Duverger E, Menegaux F, Bruning T, Harth V, Genica Network T, Severi G, Baglietto L, Southey M, Chanock SJ, Lissowska J, Figueroa JD, Eriksson M, Humphreys K, Darabi H, Olson JE, Stevens KN, Vachon CM, Knight J, Glendon G, Mulligan AM, Ashworth A, Orr N, Schoemaker M, Webb PM, Investigators K, Management Group A, Guenel P, Brauch H, Giles G, Garcia-Closas M, Czene K, Chenevix-Trench G, Couch FJ, Andrulis IL, Swerdlow A, Hunter DJ, Flesch-Janys D, Easton DF, Hall P, Nevanlinna H, Kraft P, Chang-Claude J (2013) Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study. Endocrine-related cancer

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0x10-03 were="" selected="" for="" replication="" using="" pooled="" case-control="" data="" from="" eleven="" studies="" of="" the="" breast="" cancer="" association="" consortium,="" including="" 7,689="" cases="" (676="" lobular)="" and="" 9,266="" controls.="" fixed="" effects="" meta-analysis="" was="" used="" to="" derive="" combined="" pint.="" no="" snp="" reached="" genome-wide="" significance="" in="" either="" the="" discovery="" or="" combined="" stage.="" we="" observed="" effect="" modification="" of="" current="" mht="" use="" on="" overall="" bc="" risk="" by="" two="" snps="" on="" chr13="" near="" pomp="" (combined="">