title: Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk.
abstract: BACKGROUND
  Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR).
  
  
  METHODS
  We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4 mg/dl), patients with hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided.
  
  
  RESULTS
  We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC.
  
  
  CONCLUSIONS
  Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC.
authors: Division of Gastroenterology (BB, YXY), Center for Clinical Epidemiology and Biostatistics (BB, KH, RM, YXY), Department of Biostatistics and Epidemiology (BB, KH, RM, YXY), Division of Hematology/Oncology (RM), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel (BB).
authors: Ben
authors: B
authors: Boursi
authors: Division of Gastroenterology (BB, YXY), Center for Clinical Epidemiology and Biostatistics (BB, KH, RM, YXY), Department of Biostatistics and Epidemiology (BB, KH, RM, YXY), Division of Hematology/Oncology (RM), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel (BB).
authors: Kevin
authors: K
authors: Haynes
authors: Division of Gastroenterology (BB, YXY), Center for Clinical Epidemiology and Biostatistics (BB, KH, RM, YXY), Department of Biostatistics and Epidemiology (BB, KH, RM, YXY), Division of Hematology/Oncology (RM), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel (BB).
authors: Ronac
authors: R
authors: Mamtani
authors: Division of Gastroenterology (BB, YXY), Center for Clinical Epidemiology and Biostatistics (BB, KH, RM, YXY), Department of Biostatistics and Epidemiology (BB, KH, RM, YXY), Division of Hematology/Oncology (RM), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel (BB). yangy@mail.med.upenn.edu.
authors: Yu-Xiao
authors: YX
authors: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D006980:Hyperthyroidism / Q000150:complications; D007037:Hypothyroidism / Q000188:drug therapy*; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D013963:Thyroid Hormones