June 13, 2007 Carriers of a BRCA2 variation specific to Iceland are more likely to develop aggressive and lethal prostate cancer than noncarriers, according to a new study. Mutations in the BRCA2 gene are associated with increased prostate cancer risk, but it has been unclear whether they are related to progression of the disease.
Laufey Tryggvadóttir of the Icelandic Cancer Registry and colleagues compared survival and disease progression in prostate cancer patients with the Icelandic BRCA2 999del5 founder mutation and those without the mutation. Using a pool of male relatives of women with breast cancer, researchers identified prostate cancer patients diagnosed in Iceland between 1955 and 2004. The mutation was present in 30 patients (5.7%).
The mutation's carriers were younger at the time of diagnosis and had more advanced staged cancer, higher-grade tumors, and shorter median survival time (2.1 years vs. 12.4 years) compared with noncarriers.
The authors conclude that "it is of great importance to study whether these results can be confirmed for carriers of mutations at other locations within the BRCA2 gene. Finally, the results indicate that in the search for new methods to predict prostate cancer progression, it may be fruitful to look for gene or protein expression patterns in prostate cancers resembling the patterns seen in BRCA2 mutation carriers."
In an accompanying editorial, Sholom Wacholder, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues discuss the limitations of this study and other similar studies--the small number of mutation carriers, changes in screening practices, and the assumption that the date of diagnosis corresponds with the time of disease onset.
"This work may clarify when and how BRCA2 mutations alter carcinogenesis. More generally, it offers an avenue for improving the accuracy of information available to patients when they are diagnosed with cancer. Nonetheless, the immediate clinical utility of these findings is limited, despite unusually rigorous design and analysis," the authors write.
Article: Tryggvadóttir L, Vidarsdóttir L, Thorgeirsson T, Jonasson JG, et al. Prostate Cancer Progression and Survival in BRCA2 Mutation Carriers. J Natl Cancer Inst 2007; 99: 929-935
Editorial: Wacholder S, Loukissas JK, Hartge P. Studies of Genes and Cancer Survival: Pieces of the Puzzle. J Natl Cancer Inst 2007; 99: 908-909
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