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Background  A single nucleotide polymorphism located in the 3'-untranslated region of the  KRAS  oncogene ( KRAS  variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the  KRAS  variant with sporadic and familial breast cancer and breast tumor characteristics.    Methods  Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for  BRCA1/2  mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the  KRAS  genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models.    Results  No evidence of association was observed between the  KRAS  variant and risk of sporadic and familial breast cancer - either among  BRCA  carriers or non- BRCA  carriers. The  KRAS  variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users.    Conclusion  Our data do not support the hypothesis that the  KRAS  variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the  KRAS  variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.

bmc cancer

KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study