Long-Term Use of Thyroid Hormone Replacement Linked to Decreased Risk of Colorectal Cancer

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Long-term thyroid hormone replacement was associated with a decreased risk of colorectal cancer, but hyperthyroidism and untreated hypothyroidism were associated with a modestly elevated risk, according to a study using a large population-based medical records database from the United Kingdom.

A total of 20,990 colorectal cancer patients and 82,054 control patients, exclusive of those with familial colorectal cancer syndromes or inflammatory bowel disease, were identified for this nested case-control study. Every colorectal cancer case patient was matched with four eligible control patients on age, sex, practice site, and duration of follow-up. “As expected, case patients were more likely to have a medical history of diabetes mellitus and more likely to be former or current smokers and alcohol users,” the investigators noted.

Significant Results

The results were reported in the Journal of the National Cancer Institute. Yu-Xiao Yang, MD, of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, served as the corresponding author of this article.

Patients with clinical or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels > 4 mg/dL) who were treated with thyroid hormone replacement “had lower risk of colorectal cancer, with an adjusted odds ratio of 0.92 (95% CI = 0.86–0.98, P = .009),” the researchers reported. In further analysis, thyroid hormone replacement for more than 1 year was associated with a lower colorectal cancer risk, and this protective association was stronger with increasing time.

The adjusted odds ratios for colorectal cancer associated with thyroid hormone replacement were 0.88 (95% CI = 0.79–0.99, P = .03) for treatment initiated 5 to 10 years before the index date and 0.68 (95% CI = 0.55–0.83, P < .001) for treatment initiated more than 10 years before. The protective effect of thyroid hormone replacement was also higher for patients who underwent colectomy and was more evident among women.

Among patients who did not receive thyroid hormone replacement, those with clinical or subclinical hypothyroidism had a modestly higher risk for colorectal cancer than those without documented thyroid dysfunction, with an adjusted odds ratio of 1.16 (95% CI = 1.08–1.24, P < .001). Patients with hyperthyroidism (TSH < 4 mg/dL) also had an increased risk of colorectal cancer, with an adjusted odds ratio of 1.21 (95% CI = 1.08–1.36, P = .001).

Potential Impact

“If confirmed, results from this study may help health care providers decide between early vs late treatment with thyroid hormone replacement in asymptomatic subclinical hypothyroidism or alternatively increased colonic screening in those individuals,” the investigators concluded. “Further research evaluating the chemopreventive potential of thyroid hormone replacement and the exact biological mechanism for this effect might enable more specific chemopreventive drugs in the future.”

This study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health. ■

 Boursi B, et al: J Natl Cancer Inst 107:djv084, 2015.