Colorectal Risk Cut in Half Among Patients Taking Thyroid Drug
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Taking Levothyroxine (L-thyroxine) for at least five years appears to cut the risk for colorectal cancer in half, researchers reported here today.
In a case-control study of 2,102 matched pairs, Israeli investigators reported a significant reduction in colorectal cancer risk among L-thyroxine users (odds ratio, 0.49, 95% confidence interval 0.35-0.68). L-thyroxine is sold under several brand names including Synthroid and Levothroid.
This protection was observed in the both right and left sides of the colon as well as in the rectum, reported Gad Rennert, M.D., Ph.D., of the National Cancer Control Center in Haifa at the American Association for Cancer Research’s prevention meeting.
“The effect was pretty dramatic,” Dr. Rennert said. “We have yet to understand all the mechanisms. The literature on the subject is very minimal, but the finding is very strong. It is robust.”
On the basis of data from the Molecular Epidemiology of Colorectal Cancer Study (MECC), the researchers found this association to be evident in both sexes, and in all age groups, religions, and ethnic origins. However, the association reached statistical significance specifically for Jewish females, people over age 65, and for European-American born patients.
Even after adjusting for aspirin or other non-steroidal anti-inflammatory drug (NSAID) use, statin use, a first-degree family history of colorectal cancer, vegetable consumption, and exercise, the association remained strong (OR 0.54, 95% CI 0.38-0.77). Earlier research, including a study from the Journal of American Medical Association last August, has shown aspirin and NSAID use to be associated with a lowered risk for colorectal cancer.
The MECC study is a study of incident colorectal cancer diagnosed in northern Israel between 1998 and 2004 and population-based controls who were matched for age, gender, clinic location, and religion. Dr. Rennert’s data is based on 2,102 matched pairs from the MECC cohort.
L-thyroxine use and all medications used for at least five years were self-reported during in-person interviews. L-thyroxine use was verified by checking computerized records for almost 96% of the study group.
While this 50% reduced risk finding is quite significant, Dr. Rennert said, it raises more questions than it answers. For example, he said, it’s unclear whether it’s the hypothyroidism or the drug that is protective.
“It might very well be that it’s the hypothyroidism state,” that’s producing this effect, he said, though he added he suspects the drug may play the active role here.
Dr. Rennert and his team point to some laboratory evidence that indicate it could be the drug, not the disease, that is providing these protective benefits. “Thyroid hormone suppresses the beta catenin activation of the cyclin D1 promoter,” a critical component to the pathway of colorectal cancer development, the authors said.
Hypothyroidism, they continued, is also known “to impair colonic motility and transit time,” which may contribute to a heightened risk for colorectal cancer, they said.
Dr. Rennert concluded the finding could have cancer prevention potential with further clinical exploration.
“We don’t know where this is going to take us,” he said, “but it’s an interesting finding. I hope these findings will translate into future preventive measures.”
Source: Journal of American Medical Association
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