Research article

Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women

Danielle M Friedrichsen¹ , Kathleen E Malone^2,3 , David R Doody² , Janet R Daling^2,3 and Elaine A Ostrander¹

¹  Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

²  Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

³  School of Public, Health and Community Medicine, Department of Epidemiology, University of Washington, Seattle, Washington, USA

author email corresponding author email

Breast Cancer Res 2004, 6:R629-R635doi:10.1186/bcr933

Published:	22 September 2004

Abstract

Introduction

The cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC has been associated with increased risk for breast or prostate cancer. Multiple studies have found an elevated frequency of the 1100delC variant in specific stratifications of breast cancer patients with a family history of the disease, including BRCA1/BRCA2 negative families and families with a history of bilateral disease or male breast cancer. However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America.

Methods

We report here on the frequency of three CHEK2 variants that alter protein function – 1100delC, R145W, and I175T – in 506 cases and 459 controls from a population based, case–control study of breast cancer conducted in young women from western Washington.

Results

There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; P = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; P = 0.09).

Conclusion

The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA.