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Greater Predisposition To Cancer In Those With Certain Homozygous Gene Pairs, Study Suggests

Date:
March 26, 2008
Source:
JAMA and Archives Journals
Summary:
Persons with a certain type of homozygosity (having two identical copies of the same gene, one inherited from each parent), may have a greater predisposition to cancer, according to a new study.

Persons with a certain type of homozygosity (having two identical copies of the same gene, one inherited from each parent), may have a greater predisposition to cancer, according to a new study.

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In previous research, the authors observed a low frequency of germline (those cells of an individual that have genetic material that could be passed to offspring) heterozygosity (possessing two different forms of a particular gene, one inherited from each parent) in cancer patients compared with controls, raising the question 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," the researchers write.

Charis Eng, M.D., Ph.D., of the Cleveland Clinic Foundation, and colleagues conducted a study to determine the frequency of germline homozygosity in a large series of patients with three different types of solid tumors compared with population-based controls. The study included germline and corresponding tumor DNA, which was isolated from 385 patients with carcinomas (147 breast, 116 prostate, and 122 head and neck carcinomas), and was subjected to genetic analysis.

The researchers found: "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."

"... our observations here should be validated in these solid tumors and explored in other 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," the authors write.

Journal reference: JAMA. 2008;299[12]:1437-1445.


Story Source:

The above story is based on materials provided by JAMA and Archives Journals. Note: Materials may be edited for content and length.


Cite This Page:

JAMA and Archives Journals. "Greater Predisposition To Cancer In Those With Certain Homozygous Gene Pairs, Study Suggests." ScienceDaily. ScienceDaily, 26 March 2008. <www.sciencedaily.com/releases/2008/03/080325163800.htm>.
JAMA and Archives Journals. (2008, March 26). Greater Predisposition To Cancer In Those With Certain Homozygous Gene Pairs, Study Suggests. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2008/03/080325163800.htm
JAMA and Archives Journals. "Greater Predisposition To Cancer In Those With Certain Homozygous Gene Pairs, Study Suggests." ScienceDaily. www.sciencedaily.com/releases/2008/03/080325163800.htm (accessed October 25, 2014).

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