Gene Study Helps Predict Susceptibility To Cancer

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Main Category: Cancer / Oncology
Also Included In: Genetics;  Breast Cancer;  Prostate / Prostate Cancer
Article Date: 26 Mar 2008 - 0:00 PDT

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According to an article published in JAMA, researchers have found that having two identical copies of the same gene may predispose people to cancer. The condition, called homozygosity, occurs when one copy of the same gene is inherited from each parent, say researcher Charis Eng, M.D. Ph.D. (Cleveland Clinic Foundation) and colleagues.

The authors had previously studied cancer patients and observed a low incidence of germline heterozygosity compared to controls. Germline refers to cells that have genetic material capable of being passed to offspring, and heterozygosity is the characteristics of possessing two different forms of a gene that are each inherited from a separate parent. This previous research led the authors to investigate whether homozygosity could play a role in cancer predisposition. "Homozygosity is common in humans and extended homozygote tracts have been described in several studies. Cancer susceptibility genes are also numerous in the genome. These facts together increase the likelihood that homozygosity might occur in the loci [the specific site of a particular gene on its chromosome] of cancer susceptibility genes. One can then hypothesize that germline homozygosity at these loci may somehow contribute to cancer predisposition," write the authors.

To conduct this most recent study, Eng and colleagues used a large series of patients with three types of solid tumors and compared the frequency of germline homozygosity with population-based controls. Researchers genetically analyzed the germline and corresponding tumor DNA of 385 patients with 147 breast, 116 prostate, and 122 head and neck carcinomas.

The researchers found that: "Our data derived from 3 different solid tumors, validated in a fourth, demonstrate that high frequencies of germline homozygosity at specific markers are associated with these cancers compared with controls. Importantly, we were able to independently validate our observations in a different type of solid tumor, lung carcinoma, by showing an increased frequency of germline homozygosity in cancer cases compared with ancestry-matched controls."

They also call for validation in these and other tumors and malignancies. "If our data can be robustly replicated independently, then germline homozygosity at specific loci as low-penetrance alleles [one of a number of alternative forms of the same gene occupying a given position on a chromosome] predisposing to carcinomas could be taken into account in future cancer risk assessments and management beyond high-penetrance cancer susceptibility genes. Additionally, with further studies and fine structure analyses, it may be possible to use such data to predict the likelihood of loss of heterozygosity in a tumor at specific genomic loci if we knew the relative frequencies of germline homozygosity/heterozygosity at those same loci," conclude the authors.

Frequency of Germline Genomic Homozygosity Associated With Cancer Cases
Guillaume Assié; Thomas LaFramboise; Petra Platzer; Charis Eng
JAMA (2008). 299[12]:1437-1445.
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Written by: Peter M Crosta
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