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Enzyme may help aspirin protect against colon cancer

People with low levels don’t benefit from common drug

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2:00pm, April 23, 2014

PLAYING DEFENSE  Aspirin’s protection against colorectal cancer might be limited to people with good supplies of a homegrown enzyme called 15-PGDH, a new study finds.

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Aspirin, the pain reliever that lowers fever and inhibits blood clotting, also shows impressive but spotty protection against colorectal cancer. A new study reveals that people who fail to get this benefit from the drug might be making too little of a key enzyme in the colon.

Among aspirin users, those with ample levels of the enzyme 15-PGDH are about half as likely to develop colon cancer as those with low levels of 15-PGDH. Scientists who analyzed data from two studies spanning up to three decades report the findings in the April 23 Science Translational Medicine.

Screening people’s 15-PGDH levels could help doctors counsel them about whether they could reduce their colon cancer risk by taking aspirin, says Eric Jacobs, an epidemiologist at the American Cancer Society in Atlanta who wasn’t part of the research team. Despite its pluses, aspirin can be hard on the digestive tract and cause internal bleeding.

Aspirin’s benefit against colorectal cancer has baffled researchers, providing protection in some studies and little in others (SN: 12/1/12, p. 18). Earlier research offered clues that individual predisposition might underlie the inconsistency. So Sanford Markowitz, a medical oncologist at Case Western Reserve University in Cleveland, teamed with other researchers to scan the databases for trends. The researchers had access to colorectal tissue samples from more than 125,000 people, including 270 who had developed colorectal cancer.

The researchers found that people with above-average 15-PGDH levels who took aspirin regularly were just 49 percent as likely to develop colorectal cancer as aspirin takers who had lower levels of the enzyme. Samples taken from tumors showed little or no 15-PGDH. It’s not clear whether those tissues had become cancerous as a result of missing the protective enzyme, or whether tumor growth had wiped out the enzyme, Markowitz says.

The evidence suggesting that high levels of 15-PGDH provide an anticancer benefit beyond aspirin’s makes biological sense, says Raymond DuBois, a biochemist and physician at Arizona State University in Tempe. Aspirin and other anti-inflammatory drugs — such as ibuprofen (Motrin and Advil), naproxen (Aleve) and celecoxib (Celebrex) — suppress inflammation by binding to and bogging down cyclooxygenase proteins in the body. Left to their own devices, COX proteins provide building blocks for a troublesome compound called prostaglandin E2, which instigates inflammation and cancerous growth if left unchecked.

The enzyme 15-PGDH naturally degrades prostaglandin E2, DuBois says. If some COX proteins slip past aspirin’s neutralizing effect, 15-PGDH could thwart them by sabotaging prostaglandin E2 production, he says.

The new results raise the question of whether simply making a lot of this enzyme would protect against cancer regardless of aspirin use. “Wouldn’t I love to know that,” Markowitz says.

In theory, doctors could obtain colon tissue samples during a routine colonoscopy to check 15-PGDH levels, Markowitz says. The extra biopsy and test would make sense for people at risk of colorectal cancer, such as those with a family history of it or people discovered to have polyps during a colonoscopy, Markowitz says.

“This would be very helpful for clinicians,” DuBois adds. The enzyme levels could designate people who would benefit from aspirin while eliminating others and minimizing their bleeding risk.

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