Effects of thyroid hormone imbalance on colorectal cancer carcinogenesis and risk — a systematic review
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: “((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])”. No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08–1.24, p < 0.001) to 1.69 (95% CI: 1.21–2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44–0.81, p = 0.001) to 0.92 (95% CI: 0.86–0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC.
Keywords: colorectal cancercancer riskhypothyroidismthyroid hormoneslevothyroxine
References
- Nowotwory złośliwe jelita grubego (C18-21). KRN. http://onkologia.org.pl/nowotwory-zlosliwe-jelita-grubego-c18-21/. (July 10, 2018).
- Society AC. Society AC. Survival Rates for Colorectal Cancer, by Stage.
- Brenner H, Hoffmeister M, Stegmaier C, et al. Risk of progression of advanced adenomas to colorectal cancer by age and sex: estimates based on 840,149 screening colonoscopies. Gut. 2007; 56(11): 1585–1589.
- Colussi D, Fabbri M, Zagari RM, et al. Lifestyle factors and risk for colorectal polyps and cancer at index colonoscopy in a FIT-positive screening population. United Eur Gastroenterol J. 2018; 6(6): 935–942.
- Sehdev A, O'Neil BH, Sehdev A, et al. The Role of Aspirin, Vitamin D, Exercise, Diet, Statins, and Metformin in the Prevention and Treatment of Colorectal Cancer. Curr Treat Options Oncol. 2015; 16(9): 43.
- Kobiela J, Dobrzycka M, Jędrusik P, et al. Metformin and Colorectal Cancer – A Systematic Review. Exp Clin Endocrinol Diab. 2018.
- Peeters RP, Visser TJ. Metabolism of Thyroid Hormone. MDText, South Dartmouth 2000.
- Giani C, Fierabracci P, Bonacci R, et al. Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy. J Clin Endocrinol Metab. 1996; 81(3): 990–994.
- Silva JM, Domínguez G, González-Sancho JM, et al. Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer. Oncogene. 2002; 21(27): 4307–4316.
- Lin KH, Shieh HY, Chen SL, et al. Expression of mutant thyroid hormone nuclear receptors in human hepatocellular carcinoma cells. Mol Carcinog. 1999; 26(1): 53–61.
- Sarosiek K, Gandhi AV, Saxena S, et al. Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations. J Thyroid Res. 2016; 2016: 2454989.
- Brown AR, Simmen RCM, Simmen FA, et al. The role of thyroid hormone signaling in the prevention of digestive system cancers. Int J Mol Sci. 2013; 14(8): 16240–16257.
- Catalano V, Dentice M, Ambrosio R, et al. Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling. Cancer Res. 2016; 76(5): 1237–1244.
- Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007; 445(7123): 111–115.
- Szaryńska M, Olejniczak A, Kobiela J, et al. Therapeutic strategies against cancer stem cells in human colorectal cancer. Oncol Lett. 2017; 14(6): 7653–7668.
- Todaro M, Alea MP, Di Stefano AB, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007; 1(4): 389–402.
- Zhu L, Tian G, Yang Q, et al. Thyroid hormone receptor β1 suppresses proliferation and migration by inhibiting PI3K/Akt signaling in human colorectal cancer cells. Oncol Rep. 2016; 36(3): 1419–1426.
- Puzianowska-Kuznicka M, Nauman A, Madej A, et al. Expression of thyroid hormone receptors is disturbed in human renal clear cell carcinoma. Cancer Lett. 2000; 155(2): 145–152.
- Puzianowska-Kuznicka M, Krystyniak A, Madej A, et al. Functionally impaired TR mutants are present in thyroid papillary cancer. J Clin Endocrinol Metab. 2002; 87(3): 1120–1128.
- Suzuki H, Willingham MC, Cheng SY, et al. Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. Thyroid. 2002; 12(11): 963–969.
- Dentice M, Luongo C, Ambrosio R, et al. β-Catenin regulates deiodinase levels and thyroid hormone signaling in colon cancer cells. Gastroenterology. 2012; 143(4): 1037–1047.
- Lee YS, Chin YT, Shih YJ, et al. Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer. Horm Cancer. 2018; 9(3): 156–165.
- Rennert G, Rennert HS, Pinchev M, et al. A case-control study of levothyroxine and the risk of colorectal cancer. J Natl Cancer Inst. 2010; 102(8): 568–572.
- Friedman GD, Schwalbe JS, Habel LA, et al. Re: a case-control study of levothyroxine and the risk of colorectal cancer. J Natl Cancer Inst. 2011; 103(21): 1637–1639.
- Boursi B, Haynes K, Mamtani R, et al. Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk. J Natl Cancer Inst. 2015; 107(6): djv084.
- Mu G, Mu X, Xing H, et al. Subclinical hypothyroidism as an independent risk factor for colorectal neoplasm. Clin Res Hepatol Gastroenterol. 2015; 39(2): 261–266.
- Chan YiX, Alfonso H, Chubb SA, et al. Higher thyrotropin concentration is associated with increased incidence of colorectal cancer in older men. Clin Endocrinol (Oxf). 2017; 86(2): 278–285.
- Chen YK, Lin CL, Cheng FTF, et al. Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study. Br J Cancer. 2013; 109(9): 2496–2501.
- Chen YK, Lin CL, Chang YJ, et al. Cancer risk in patients with Graves' disease: a nationwide cohort study. Thyroid. 2013; 23(7): 879–884.
- Guillem-Llobat P, Dovizio M, Bruno A, et al. Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells. Oncotarget. 2016; 7(22): 32462–32477.
- Chopra IJ, Chopra IJ. An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man. J Clin Invest. 1976; 58(1): 32–40.
- Dobrzycka M, Spychalski P, Łachiński AJ, et al. Statins and Colorectal Cancer — A Systematic Review. Exp Clin Endocrinol Diabetes. 2018 [Epub ahead of print].
- Pearce SHS, Brabant G, Duntas LH, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013; 2(4): 215–228.
