REYKJAVIK, Iceland, Jan. 18 Scientists at deCODEgenetics (Nasdaq: DCGN) and colleagues from the US and ten European countriestoday announced a long-awaited first in cancer research: the discovery ofcommon single-letter variations in the human genome (SNPs) linked tosusceptibility not of one, but several different types of cancer, includingthose of lung, bladder, prostate, skin and cervix.
Over the past two years, deCODE has led a wave of discoveries byscientists around the world of common SNPs conferring risk of many major typesof cancer. Yet without exception, these SNPs have been linked to cancer ofonly one or at most two tissue types or organs. The SNPs published today,located near each other on chromosome 5p15, may therefore help to tag majorbiological mechanisms underlying cancer susceptibility more generally. Thepaper, entitled "Sequence variants at the TERT-CLPTM1L locus associate withmany cancer types," is published today in the online edition of NatureGenetics at www.nature.com/ng, and will appear in an upcoming print edition ofthe journal.
"Today's findings demonstrate the power of using genetics to advance ourunderstanding of the biology of cancer and to discover new strategies forassessing and reducing risk. Our next task is to discover how these SNPsaffect susceptibility. One plausible, but as yet unproven, explanation is thatthese variants provide a genetic background that determines how our bodiesrespond to environmental risk factors. A thread connecting these differentcancer types is that most have important known environmental risk factors andall tend to arise in the tissue layers directly exposed to the environment.One of the SNPs we have discovered is in a gene involved in determining thelength of the telomeres, or the tail ends of chromosomes. Shorter telomereshave recently been linked to risk of certain cancers, and telomeres are knownto become shorter with the accumulation of environmental insults over time.These findings may point us towards a means of addressing these risks byaltering our lifestyle or by helping to identify targets for new drugs. We areintegrating the SNPs into deCODEme(TM), and into our deCODEme Cancer Scan(TM)launched today," said Kari Stefansson, CEO of deCODE and senior author on thepaper.
deCODE discovered the first variant, a SNP called rs 401681, in its genediscovery 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 cancerbiology, the deCODE team then tested this SNP for association with 16different types of cancer in a total of nearly 80,000 cancer patients andhealthy control subjects from Iceland, the Netherlands, Italy, Sweden, Spain,Germany, Hungary, the United Kingdom, Belgium, Romania, Slovakia and theUnited 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 foundto protect against melanoma. It is of interest here that the risks of cancersof lung, bladder, prostate and cervix are greater in individuals with shortertelomeres than long, whereas those with long telomeres are at greater risk ofmelanoma. Through a more detailed analysis of this region, another SNP,rs2736089, was associated with increased risk of BCC and also with risk ofcancer of the lung, bladder and prostate. Rs 2736089 is located in the geneencoding the human telomerase reverse transcriptase (TERT), which directs theaddition of repeat DNA sequences to the ends of chromosomes. Importantly, therisk of these different cancers conferred by these two SNPs appears to beindependent.
deCODE thanks the many thousands of individuals who participated in thisstudy, as well as the collaborating researchers and institutions. This studywas funded in part by the European Commission through the POLYGENE (LSHC-CT-2005-018827) and GENADDICT (LSHM-CT-2004-005166) grants; by the US NationalInstitutes of Health (R01-DA017932); a research investment grant of theRadboud University Nijmegen Medical Centre; and through numerous grants tocollaborating institutions.
deCODE is a bio-pharmaceutical company developing drugs and DNA-basedtests to improve the treatment, diagnosis and prevention of common diseases.Its lead therapeutic programs, which leverage the company's expertise inchemistry and structural biology, include DG041, an antiplatelet compoundbeing developed for the prevention of arterial thrombosis; DG051 and DG031,compounds targeting the leukotriene pathway for the prevention of heartattack; and DG071 and a platform for other PDE4 modulators with therapeuticapplications in Alzheimer's disease and other conditions. deCODE is a globalleader in human genetics, and has identified key variations in the genome(SNPs) conferring increased risk of major public health challenges fromcardiovascular disease to cancer. Based upon these discoveries deCODE hasbrought to market a growing range of DNA-based tests for gauging risk andempowering prevention of common diseases. Through its CLIA-registeredlaboratory, deCODE is offers deCODE T2(TM) for type 2 diabetes; deCODE AF(TM)for atrial fibrillation and stroke; deCODE MI(TM) for heart attack; deCODEProstateCancer(TM) for prostate cancer; deCODE Glaucoma(TM) for a major typeof glaucoma; and deCODE BreastCancer(TM), for the common forms of breastcancer. deCODE is delivering on the promise of the new genetics(SM). Visit uson the web at www.decode.com; on our diagnostics site atwww.decodediagnostics.com; for our pioneering personal genome analysis serviceand focused disease scans, integrating the genetic variants included in thesetests and those linked to another twenty common diseases, at www.decodeme.com;and on our blog at www.decodeyou.com.
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SOURCE deCODE genetics