Determining joint carrier probabilities of cancer-causing genes using Markov chain Monte Carlo methods
Article first published online: 15 JUL 2005
© 2005 Wiley-Liss, Inc.
Volume 29, Issue 2, pages 141–154, September 2005
How to Cite
Biswas, S. and Berry, D. A. (2005), Determining joint carrier probabilities of cancer-causing genes using Markov chain Monte Carlo methods. Genet. Epidemiol., 29: 141–154. doi: 10.1002/gepi.20082
- Issue published online: 10 AUG 2005
- Article first published online: 15 JUL 2005
- Manuscript Accepted: 13 APR 2005
- Manuscript Received: 18 JAN 2005
- genetic counseling;
- ovarian cancer cluster region (OCCR);
- breast cancer;
- ovarian cancer;
- prostate cancer
In genetic counseling for cancer risk, the probability of carrying a mutation of a cancer-causing gene plays an important role. Family history of various cancers is important in calculating this probability. BRCAPRO (Parmigiani et al.  Am J Hum Genet 62:145–158) is a widely used software for calculating the probability of carrying mutations in BRCA1 and BRCA2 genes given the family history of breast and ovarian cancer in first- and second-degree relatives. BRCAPRO uses an analytical (exact) calculational procedure. Using Markov chain Monte Carlo (MCMC) methods, we extend BRCAPRO to handle, in principle, any type of cancer, family history, any number of genes and alleles that each gene may have. When the information used in this MCMC approach is the same as for BRCAPRO (two genes: BRCA1 and BRCA2; two cancers: breast and ovarian; first- and second-degree relatives only), the two approaches give essentially the same answer. Extending the model to include (1) prostate cancer, (2) two mutated alleles of BRCA2, namely, mutations in Ovarian Cancer Cluster Region (OCCR) and non-OCCR region, and (3) relatives of degree greater than second-degree, leads to different carrier probabilities. The MCMC approach is a useful tool in building a comprehensive model to give accurate estimates of carrier probabilities. Such an approach will be even more important as additional information about the genetics of various cancers becomes available. Genet. Epidemiol. 2005. © 2005 Wiley-Liss, Inc.