Scientists discover common gene that more than doubles the risk of cancer

SAN DIEGO, Calif. — Evolution is the historical key to humans becoming what are today. While that process has helped mankind to separate itself from species like chimpanzees, it has also brought some unwelcome genes along for the ride. Researchers at the University of California-San Diego have discovered a common gene that more than doubles the human risk of cancer.

Their study finds this protein fuels breast, prostate, lung, bowel, and other deadly tumors. These growths start in epithelial tissue, the outer lining of skin or organs.

Researchers say the mutation is carried by a third of the global population, making it possible to detect using a simple urine test. The discovery sheds light on why we are more prone to cancer than chimpanzees, our closest evolutionary cousins.

The human cancer gene?

Drugs that target the gene, called SIGLEC12, could prevent or even cure the disease. The findings also offer hope of a screening program for cancer.

“At some point during human evolution, the SIGLEC12 gene — and more specifically, the Siglec-12 protein it produces as part of the immune system — suffered a mutation that eliminated its ability to distinguish between ‘self’ and invading microbes, so the body needed to get rid of it,” says senior author Dr. Ajit Varki, in a university release. “But it’s not completely gone from the population — it appears that this dysfunctional form of the Siglec-12 protein went rogue and has now become a liability for the minority of people who still produce it.”

Unlike great apes, humans are vulnerable to advanced carcinomas irrespective of their genetic predisposition to get cancer or if they use tobacco. Prof. Varki adds siglecs are typically expressed in immune cells and it was surprising to find them on epithelial surfaces.

While a mutant form is expressed only in about 30 percent of normal humans, researchers found them in a high proportion of advanced carcinomas. The UC San Diego teams says this could help explain why humans are more prone to aggressive cancers, which are rare in chimpanzees.

Their analysis of cancerous and healthy tissue found carriers of this gene face over twice the risk of advanced cancer during their lifetime. This is compared to the two in three people who cannot produce Siglec-12 proteins. Normally, genes that encode dysfunctional proteins are eliminated by the body over time.

Unlocking hidden dangers

Scientists have long suspects this gene had no functional relevance. There have been very few follow-up studies over the two decades since it was discovered. Prof. Varki and the team set out to detect it in non-cancerous tissue samples using an antibody against the protein. About 30 percent of the samples came back positive, as expected from the genetic information. In contrast, the majority of advanced cancer samples from the same populations contained Siglec-12.

Looking at a different group of patients with advanced stage bowel cancer, the researchers uncovered more than 80 percent had the functional form of the gene. They had worse outcomes than the group living without it.

“These results suggest that the minority of individuals who can still make the protein are at much greater risk of having an advanced cancer,” study co-author Nissi Varki says.

Could discovery lead to way of stopping cancer at its source?

Experiments on mice injected with tumor cells engineered to produce Siglec-12 confirmed the results. The tumors grew much faster and turned on many biological pathways known to be involved in advanced cancers compared to cancers without functioning Siglec-12. Study authors say the findings could be leveraged for future diagnostics and treatments and their urine test specifically detects the presence of the dysfunctional protein.

“We might also be able to use antibodies against Siglec-12 to selectively deliver chemotherapies to tumor cells that carry the dysfunctional protein, without harming non-cancerous cells,” Ajit Varki concludes.

The study of this gene appears in the journal FASEB BioAdvances.

SWNS reporter Mark Waghorn contributed to this report.

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