Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Abstract

Introduction: Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods: We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results: Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion: Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.

Figure 1

Age at breast cancer diagnosis according to rs3803663 (TNRC9) genotype in the ORIGO cohort. The age at diagnosis in the Dutch hospital-based ORIGO cohort of breast cancer patients is represented by four age categories: before the age of 40 years, between the ages of 40 years and 50 years, between the ages of 50 years and 60 years, and above the age of 60 years. wt/wt, patients homozygous for the wildtype or major allele; wt/mt, patients heterozygous for the wildtype and mutated or minor allele; mt/mt, patients homozygous for the mutant or minor allele.