Research article

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

Petra EA Huijts¹ , Maaike PG Vreeswijk² , Karin HG Kroeze-Jansema² , Catharina E Jacobi³ , Caroline Seynaeve⁴ , Elly MM Krol-Warmerdam⁵ , Pauline M Wijers-Koster⁶ , Jannet C Blom⁴ , Karen A Pooley⁷ , Jan GM Klijn⁴ , Rob AEM Tollenaar⁵ , Peter Devilee^2,6 and Christi J van Asperen¹

¹  Department of Clinical Genetics, K5-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

²  Department of Human Genetics, S4-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

³  Department of Medical Decision Making, J10-S, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

⁴  Department of Medical Oncology, Family Cancer Clinic, Erasmus MC–Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands

⁵  Department of Surgery, K6-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

⁶  Department of Pathology, L1-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

⁷  Cancer Research UK, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN UK

author email corresponding author email

Breast Cancer Research 2007, 9:R78doi:10.1186/bcr1793

Published:	12 November 2007

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.