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Genetic Analysis Identifies Alleles Predisposing to Cancer

Study included patients with breast, prostate, and head and neck cancers

TUESDAY, March 25 (HealthDay News) -- A genetic analysis of a large group of patients with cancers of the breast, prostate, and head and neck revealed a high frequency of germline homozygosity at specific sites, suggesting that these loci may represent cancer susceptibility genes, according to research published in the March 26 issue of the Journal of the American Medical Association.

Guillaume Assie, M.D., Ph.D., of the Cleveland Clinic Foundation in Ohio, and colleagues utilized genome-wide microsatellite analysis to investigate the frequency of germline homozygosity in 385 patients with carcinomas of the breast, prostate, and head and neck. In addition, the researchers studied the frequency of somatic loss of heterozygosity in cancers at loci with the highest homozygosity.

The researchers identified 16 loci in common to the three cancer types that were associated with increased germline homozygosity in cancer patients compared to controls. Furthermore, in patients who were germline heterozygous at sites with increased germline homozygosity, the average loss of heterozygosity frequency was significantly increased compared to sites without increased germline homozygosity. This relationship was then validated in an independent data set of 205 patients with lung carcinomas.

"If our data can be robustly replicated independently, then germline homozygosity at specific loci as low-penetrance alleles predisposing to carcinomas could be taken into account in future cancer risk assessments and management beyond high-penetrance cancer susceptibility genes," the authors conclude.

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