title: KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medical Genetics, Department of Obstetrics and Gynecology, Ljubljana, Slovenia.
authors.forename: Jasmina-Ziva
authors.initials: JZ
authors.lastname: Cerne
authors.forename: Vida
authors.initials: V
authors.lastname: Stegel
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak
authors.forename: Srdjan
authors.initials: S
authors.lastname: Novakovic
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D020249:Hormone Replacement Therapy; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D017698:Postmenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017524:Slovenia
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human