Abstract
Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10−12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10−11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.
Highlights
Since the completion of the Human Genome Project, the Genome Wide Association Scan (GWAS) has become the tool of choice for the detection of associations between disease risk and common genetic variation
To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098)
All subjects had greater than 95% genotyping success rate. 26 pairs of individuals were identified with Identity by State (IBS) > 30%, with the subject having the most complete genotype data from each pair retained for analyses. 551 further individuals were excluded from the present study due to Principal Components Analysis (PCA) analyses
Summary
Since the completion of the Human Genome Project, the Genome Wide Association Scan (GWAS) has become the tool of choice for the detection of associations between disease risk and common genetic variation. GWAS studies with cases selected based on the estrogen receptor (ER) status of their tumors, and control subjects not affected by breast cancer, have shown divergent associations between ER+ and ER- tumors In these analyses, variants in FGFR2 are more strongly associated with ER+ disease [4,5,6,7,8,9,10,11,12,13,14], as opposed to ERdisease, when comparing cases to healthy controls. Analyses by subtype are often secondary, based on findings of the primary analyses of overall breast cancer risk These studies are carried out in large consortia with the potential for heterogeneity in definitions of various case characteristics, ER and HER2 status
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