1. ¹Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
2. ²Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
3. ³Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway
4. ⁴Faculty of Medicine, University of Oslo, Postboks 1171 Blindern, N0318 Oslo, Norway
5. ⁵Department of Radiation Physics, Unit 544, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA
6. ⁶Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue USC/Norris Comprehensive Cancer Center NOR-4435, Los Angeles, CA 90089-9175, USA
7. ⁷Department of Epidemiology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
8. ⁸Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B814, Seattle, WA 98109, USA
9. ⁹Department of Oncology, The Finsen Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen DK-2100, Denmark
10. ¹⁰Department of Biochemistry and Molecular Genetics, University of Virginia, PO Box 800733, Charlottesville, VA 22908, USA
11. ¹¹Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, 3rd Floor, New York, NY 10021, USA
12. ¹²International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, MD 20850, USA
13. ¹³Department of Medicine, Vanderbilt University Medical Center, 21st Avenue South and Garland Avenue, Nashville, TN 37232, USA

Correspondence: Dr L Mellemkjær, E-mail: lene@cancer.dk

¹⁴See Appendix.

Received 4 July 2007; Revised 19 December 2007; Accepted 7 January 2008; Published online 5 February 2008.

Abstract

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2^*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2^*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985–1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2^*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6–5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8–8.7). We found no significant associations between the CHEK2^*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.