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Nobel Laureate-led Team Using Genetics to Prospect for Cattle Viruses with Possible Colorectal Cancer Links

CHICAGO (GenomeWeb News) – A German team led by Nobel Laureate Harald zur Hausen is using DNA and RNA sequencing as part of its search for unknown animal pathogens with possible roles in human cancer.

In particular, zur Hausen — a German Cancer Research Center investigator best known for discovering a role for high risk human papillomaviruses in cervical cancer — contends that the consumption of beef-borne viruses carried by some types of cattle could theoretically be contributing to rising colorectal cancer rates in some countries.

Roughly one-fifth of cancer cases worldwide are linked to some manner of infectious event, zur Hausen explained, from hepatitis B viruses causing liver cancer and high-risk forms of HPV in cervical cancer to bladder cancer-causing schistosome parasites.

Along with looking at types of cancer that are more or less common in individuals with immunosuppression, he argued that there may be situations where infectious agents are behind apparent nutritional cancer risks.

Speaking at a plenary session for the American Society of Clinical Oncology annual meeting here this weekend, zur Hausen presented epidemiological data suggesting colorectal cancer rates have steadily crept up in parts of the world where beef and dairy imports have increased, including Korea and post-World War II Japan.

But that apparent correlation between colorectal cancer risk and red meat consumption was not universal.

Colorectal cancer rates tended to be high in places where Bos taurus, or "taurine," cattle are usually consumed, zur Hausen said. On the other hand, prevalence of the disease tended to be lower in locales where Bos indicus, or "indicine" cattle, yaks, and other red meat sources are more common such as Mongolia.

And because grilled, roasted, and otherwise-singed chicken and fish have not been associated with colorectal cancer risk, he argued that previously described links between colorectal cancer risk and red meat consumption might stem from cattle viruses ingested in undercooked, raw, or dried beef rather than from aromatic hydrocarbons formed while cooking.

Zur Hausen presented some of the same epidemiological evidence for his argument in a 2012 paper in the International Journal of Cancer.

To begin testing this beef virus hypothesis further, he and his colleagues used sequencing to search for new viral sequences in serum from European cattle.

When they sequenced DNase and RNase degradation-resistant particles in five pooled serum samples from 130 healthy B. taurus cattle from Europe, the researchers narrowed in on 18 new, single-stranded circular DNA molecules that were somewhat related to viruses in the Anellovirus and Circovirus families.

An assessment of the first five isolates suggested that these would-be viruses are between 1,000 and 2,200 bases apiece. More extensive testing on one of the isolates indicated that it is not found in colon cancer lines, zur Hausen said, though the team reportedly saw signs that it could be transmitted to — and persist in — human cells.

He and his colleagues are continuing to explore possible roles for these and other potentially infectious agents in colon cancer and other disease types. If so, zur Hausen speculated that there may be opportunities to prevent some cancer cases by pre-emptively vaccinating risk virus-carrying animals.

"If it turns out that some of these agents are responsible for chronic types of diseases … there may be new modes available or possible for the prevention of those types of cancer or other diseases linked to these kinds of infection," he said.