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deCODE Discovers First Common Genetic Variants Affecting the Risk of Many Types of Cancer
News

deCODE Discovers First Common Genetic Variants Affecting the Risk of Many Types of Cancer

deCODE Discovers First Common Genetic Variants Affecting the Risk of Many Types of Cancer
News

deCODE Discovers First Common Genetic Variants Affecting the Risk of Many Types of Cancer

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Scientists at deCODE genetics and colleagues from the US and ten European countries have announced a long-awaited first in cancer research: the discovery of common single-letter variations in the human genome (SNPs) linked to susceptibility not of one, but several different types of cancer, including those of lung, bladder, prostate, skin and cervix.

Over the past two years, deCODE has led a wave of discoveries by scientists around the world of common SNPs conferring risk of many major types of cancer. Yet without exception, these SNPs have been linked to cancer of only one or at most two tissue types or organs.

The SNPs located near each other on chromosome 5p15, may therefore help to tag major biological mechanisms underlying cancer suseptibility more generally. The paper, entitled “Sequence variants at the TERT-CLPTM1L locus associate with many cancer types,” is published in the online edition of Nature Genetics at www.nature.com/ng, and will appear in an upcoming print edition of the journal.

deCODE discovered the first variant, a SNP called rs 401681, in its gene discovery work on basal cell carcinoma (BCC), a common form of skin cancer. The SNP is in the gene encoding cisplatin resistance related protein 9 (CLPTM1L). Because the region of chromosome 5p15 is of interest in cancer biology, the deCODE team then tested this SNP for association with 16 different types of cancer in a total of nearly 80,000 cancer patients and healthy control subjects from Iceland, the Netherlands, Italy, Sweden, Spain, Germany, Hungary, the United Kingdom, Belgium, Romania, Slovakia and the United States.

Rs 401681 was found to confer increased risk not only of BCC, but also cancer of the lung, bladder, prostate and cervix, and was also found to protect against melanoma. It is of interest here that the risks of cancers of lung, bladder, prostate and cervix are greater in individuals with shorter telomeres than long, whereas those with long telomeres are at greater risk of melanoma.

Through a more detailed analysis of this region, another SNP, rs2736089, was associated with increased risk of BCC and also with risk of cancer of the lung, bladder and prostate. Rs 2736089 is located in the gene encoding the human telomerase reverse transcriptase (TERT), which directs the addition of repeat DNA sequences to the ends of chromosomes.

Importantly, the risk of these different cancers conferred by these two SNPs appears to be independent.
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