Updated 30 March 2017

One gene, two cancers?

Compelling evidence from four studies confirms that a key change in DNA previously linked to prostate cancer also raises colon cancer risk, scientists report.

Compelling evidence from four studies confirms that a key change in DNA previously linked to prostate cancer also raises colon cancer risk, scientists report.

They stress that the risk to any individual carrier of the rs6983267 variant gene - which is located on a region of chromosome 8 called 8q24 - are relatively slight. Overall, carriers of this variant have about a 20 percent higher risk of developing a colourectal malignancy compared to non-carriers, the researchers said.

The gene's real power comes in its prevalence.

According to scientists, the number of people who carry the variant on region 8q24 includes about half of the populations studied, researchers say.

Very common
"In other words, it is very common in the general population," said Dr Malcolm Dunlop, of Cancer Research UK and the University of Edinburgh, Scotland.

Dunlop, the lead investigator on one of three studies published in the July 8 online edition of Nature Genetics, told reporters at a Friday news conference that "between 4 to 9 percent of all bowel cancers" may be traced to this particular chromosomal locus.

His team honed in on the 8q24 region after comparing the genomes of almost 7 500 colon cancer patients against those of almost 7 800 unaffected controls.

Similar results were found in a US study that was led by Christopher Haiman of the University of Southern California, Los Angeles. His team combed through the DNA of more than 1 800 people from a variety of racial and ethnic backgrounds; comparing key differences in DNA against genes from more than 5 500 healthy controls.

Similar risk observed
Again, the rs6983267 variant conferred about a 22 percent increase in colourectal cancer risk, Haiman's team reported. Prior studies had already tied this variant to an increased risk for prostate cancer.

"This is the first common genetic risk factor that has been reproducibly associated with risks in multiple cancers," Haiman told reporters. "The association observed with this variant in both prostate and colourectal cancer provides very strong support for the hypothesis that there may be a common biological mechanism underlying cancer risk in this region of the genome."

The California team stressed that the level of risk to an individual conferred by the gene did not change, regardless of the person's sex, race, site of tumour, tumour stage or the presence of colon cancer risk factors such as family history, smoking or drinking.

However, rs6983267 was found more frequently in some ethnicities than in others. "The frequency of this specific genetic variation varies widely in the population," Haiman said.

Another researcher noted that genes like the one in region 8q24 are often more dangerous when they clump together in the same person.

Genetic risks may ad up
"Although individually these markers may only contribute small amounts of risk, collectively, in certain individuals, they may actually have composite risks which are comparable to that of known, high-risk [mutations]," explained Dr Richard Houlston, of the Institute of Cancer Research in Sutton, UK

Comparing genomic differences among 930 people with colourectal cancer and 960 controls, his team also zeroed in on rs6983267 as boosting tumour risk. Given the genes' link to prostate cancer, "it does tend to suggest that some of these things may actually have a generic effect on more than one malignancy," Houlston said at the press conference.

A fourth study - this time led by a consortium from Israel, Spain and the United States - uncovered a similar connection between genetic variations on 8q24 and a rise in colon cancer risk. That research was published in the July issue of Cancer Biology and Therapy.

No immediate implications
While intriguing, experts agreed that the finding does not have immediate implications for the detection, prevention and treatment of colourectal cancer.

"These are encouraging findings, but obviously we need a lot more information about the genetic implications," said Dr Durado Brooks, the society's director of prostate and colourectal cancer. Genetic tests that might assess people's risk or help in cancer diagnosis are still years away, and, for now, the new finding "will not in any way significantly alter clinical practice," he said.

Still, the assembled experts agreed that clinical application remains the ultimate goal of their research efforts.

Ideally, Dunlop said, tests might someday be developed to spot genes like rs6983267, "such that you could tailor interventions such as more intensive [patient] surveillance and even prevention," he said. "This is a big step forward, but there is more to come." – (HealthDayNews)

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Prostate Centre
Cancer Centre

July 2007


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