ORIGINAL ARTICLE

The effect of a single BRCA2 mutation on cancer in Iceland

H Tulinius^1,2, G H Olafsdottir¹, H Sigvaldason¹, A Arason³, R B Barkardottir³, V Egilsson³, H M Ogmundsdottir^1,2, L Tryggvadottir¹, S Gudlaugsdottir¹ and J E Eyfjord^1,2

¹ Icelandic Cancer Society, Reykjavik, Iceland
² University of Iceland, Reykjavik, Iceland
³ Laboratory of Cell Biology, Department of Pathology, University of Iceland, Reykjavik, Iceland

Correspondence to:
Correspondence to:
Dr H Tulinius, Icelandic Cancer Registry, Skogarhlid 8, PO Box 5420, 125 Reykjavik, Iceland;
hrafnt{at}krabb.is

Objective: To estimate the risk of malignant diseases in families of probands with the same mutation in the BRCA2 gene.

Design: A cohort study using record linkage of a breast cancer family resource and the Icelandic Cancer Registry.

Setting: Iceland.

Subjects: Families of 995 breast cancer patients, from which 887 were tested for a single founder 999del5 mutation; 90 had the mutation and 797 did not.

Results: Relatives of probands with the mutation had significantly increased relative risk (RR) of breast cancer. For first degree relatives, the RR was 7.55 (95% CI 6.04 to 9.03) but was 1.72 (95% CI 1.49 to 1.96) in first degree relatives of probands without the mutation. For prostate and ovarian cancer, the first and second degree relatives of probands with the mutation had a significantly increased RR, but in families of probands without the mutation no significant familial risk was found.

Conclusions: The 999del5 mutation in the BRCA2 gene explains a substantial proportion of familial risk of breast cancer in Iceland, but significant familial risk remains in relatives of probands without the mutation. For prostate and ovarian cancer, the mutation accounts for most of the familiality observed in families of breast cancer patients.

Keywords: epidemiology; cohort study; familiality;

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Agalliu, I., Gern, R., Leanza, S., Burk, R. D. (2009). Associations of High-Grade Prostate Cancer with BRCA1 and BRCA2 Founder Mutations. Clin. Cancer Res. 15: 1112-1120 [Abstract] [Full Text]  
• Ostrander, E. A., Udler, M. S. (2008). The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited. Cancer Epidemiol. Biomarkers Prev. 17: 1843-1848 [Abstract] [Full Text]  
• Willems, A. J., Dawson, S.-J., Samaratunga, H., De Luca, A., Antill, Y. C., Hopper, J. L., Thorne, H. J., and kConFab Investigators, (2008). Loss of Heterozygosity at the BRCA2 Locus Detected by Multiplex Ligation-Dependent Probe Amplification is Common in Prostate Cancers from Men with a Germline BRCA2 Mutation. Clin. Cancer Res. 14: 2953-2961 [Abstract] [Full Text]  
• Tryggvadottir, L., Vidarsdottir, L., Thorgeirsson, T., Jonasson, J. G., Olafsdottir, E. J., Olafsdottir, G. H., Rafnar, T., Thorlacius, S., Jonsson, E., Eyfjord, J. E., Tulinius, H. (2007). Prostate Cancer Progression and Survival in BRCA2 Mutation Carriers. JNCI J Natl Cancer Inst 99: 929-935 [Abstract] [Full Text]  
• Agalliu, I., Kwon, E. M., Zadory, D., McIntosh, L., Thompson, J., Stanford, J. L., Ostrander, E. A. (2007). Germline Mutations in the BRCA2 Gene and Susceptibility to Hereditary Prostate Cancer. Clin. Cancer Res. 13: 839-843 [Abstract] [Full Text]  
• Risch, H. A., McLaughlin, J. R., Cole, D. E. C., Rosen, B., Bradley, L., Fan, I., Tang, J., Li, S., Zhang, S., Shaw, P. A., Narod, S. A. (2006). Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada. JNCI J Natl Cancer Inst 98: 1694-1706 [Abstract] [Full Text]  
• Tryggvadottir, L., Sigvaldason, H., Olafsdottir, G. H., Jonasson, J. G., Jonsson, T., Tulinius, H., Eyfjord, J. E. (2006). Population-Based Study of Changing Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers, 1920-2000. JNCI J Natl Cancer Inst 98: 116-122 [Abstract] [Full Text]  
• van Asperen, C J, Brohet, R M, Meijers-Heijboer, E J, Hoogerbrugge, N, Verhoef, S, Vasen, H F A, Ausems, M G E M, Menko, F H, Gomez Garcia, E B, Klijn, J G M, Hogervorst, F B L, van Houwelingen, J C, van't Veer, L J, Rookus, M A, van Leeuwen, F E, on behalf of the Netherlands Collaborative Group o, (2005). Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J. Med. Genet. 42: 711-719 [Abstract] [Full Text]  
• Liede, A., Karlan, B. Y., Narod, S. A. (2004). Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature. JCO 22: 735-742 [Abstract] [Full Text]