Genetic Variation Cuts Bladder Cancer Risk

Scientists have discovered a common genetic variation linked to reduced risk of bladder cancer and to the length of protective caps found at the end of chromosomes. These endings or tips, called telomeres, guard against chromosomal damage and genomic instability that can lead to cancer and other diseases.

"We found a single point of variation in the genome strongly associated with a 19 percent decrease in bladder cancer risk. The same variant also is linked to longer telomeres, which accounts for part of the overall reduction in risk," said first author Jian Gu, assistant professor in MD Anderson's Department of Epidemiology.

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Telomere length diminishes with age and short telomeres are associated with age-related diseases such as stroke, Alzheimer's disease, diabetes, cardiovascular disease and cancer, said Gu.

Previous studies separately tied telomere length either to cancer risk or to genetic variation. The paper by Gu and colleagues is the first to make both connections.

"Understanding the complex genetic regulation of telomere length and its relation to the causes of bladder and other types of cancer will help develop therapies or lifestyle changes to reduce cancer risk," said senior author Xifeng Wu.

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Researchers first conducted a genome-wide association study to identify genetic variations associated with telomere length. They analyzed more than 300,000 single nucleotide polymorphisms (SNPs), common points of variation in the genome, in 459 healthy controls.

This narrowed the field to 15,120 SNPs, which were then validated in 1,160 healthy controls in two independent populations. They selected the top four SNPs that were associated with telomere length across all three populations for the bladder cancer association study.

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The team evaluated the association of these four sites with the risk of bladder cancer in a case-control study of 969 patients and 946 controls. Only one, a SNP on chromosome 14 known as rs398652, was associated with bladder cancer risk.

Since the SNP was associated with both telomere length and bladder cancer risk, the team conducted a mediation analysis to determine whether the effect on telomere length caused some of the risk reduction. Telomere length accounted for 14 percent of the SNP's effect on bladder cancer.

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The findings were presented at the AACR annual meeting and simultaneously published in Cancer Prevention Research, an AACR journal.

Source-ANI