Scientists discover common variants in the human genome conferring risk of bladder cancer

Sep 14 2008

Scientists at deCODE genetics and colleagues at Radboud University Medical Center in the Netherlands today report the discovery of two common single-letter variants in the human genome (SNPs) that confer increased risk of urinary bladder cancer.

Approximately 20% of people of European descent carry two copies of the first variant, a version of a SNP on chromosome 8q24, putting them at a 50% higher risk of developing bladder cancer than those without the variant. Individuals who carry two copies of a common version of another SNP on chromosome 3 were found to be at a 40% higher risk of the disease than non-carriers. These are the best-replicated genetic variants ever linked to bladder cancer risk, and the study analyzed genotypic data from more than 40,000 patients and controls from Iceland, the Netherlands and eight other European countries. The paper, entitled 'Sequence variant on 8q24 confers susceptibility to urinary bladder cancer,' will appear today in the online edition of Nature Genetics.

"In all cancers, the ability to identify individuals at high risk, screening them intensively and intervening early, is the key to improving prevention and outcomes. We expect that the detection of these and other risk variants will soon be employed to complement the assessment of standard risk factors for bladder cancer. As with all of our discovery work, we seek to publish our findings and establish a solid intellectual property position in order to bring these swiftly into the healthcare arena, and have already folded today's findings into our deCODEme(TM) personal genome analysis service. At the same time, we are working to identify the common thread of variants we and others have discovered on chromosome 8q24 that confer risk of several forms of cancer, including prostate, breast, colorectal and now bladder. If a common molecular mechanism exists, it could provide an important insight into oncogenesis more broadly," said Kari Stefansson, CEO of deCODE.

For a more detailed discussion of today's findings you can watch a video discussion between Dr. Stefansson and Dr. Simon Stacey on our blog, at www.decodeyou.com.

Urinary bladder cancer is the sixth most common type of cancer in the United States. It is estimated that 68,810 individuals will be diagnosed with bladder cancer in the United States during 2008 and that 14,100 people will die of the disease. Bladder cancer has been linked to exposure to various types of toxic substances such as cigarette smoke and industrial chemicals. Although it has been known for some time that genetic factors also play a significant role, identifying validated genetic risk variants had been problematic. Incidence of bladder cancer varies considerably between ethnicities, and as the risk factors reported here were discovered by analyzing DNA from groups of European descent, it is our hope that the publication of these findings will contribute to the swift analysis of the impact of these variants in cohorts of other continental ancestries.

The authors wish to thank the thousands of patients and control subjects who participated in this study, and acknowledge the assistance of national cancer registries that worked to identify potential participants. Data and sample collection in Iceland and the Netherlands was funded in part by European commission grants LSHC-CT-2005-018827 and LSHM-CT-2004-005166.

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