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Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a

Yuxian Chen1, Hao Dong1, Baozhen Qu2

  • 1College of Medicine, Qingdao University, Qingdao, China.

Frontiers in Endocrinology
|April 30, 2024
PubMed

Insights

Higher free thyroxine (FT4) levels may reduce biliary tract cancer (BTC) risk, potentially mediated by metabolic syndrome and waist circumference. This finding offers insights into hepatobiliary cancer prevention.

Area of Science:

  • Endocrinology
  • Oncology
  • Genetics

Background:

  • Hepatobiliary cancer (HBC), encompassing hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is a significant cause of cancer mortality.
  • Late-stage diagnosis of HBC increases disease burden, highlighting the urgent need for effective prevention strategies and risk factor identification.
  • Thyroid hormones have been implicated in HBC, prompting research into their specific roles.

Purpose of the Study:

  • To assess the causal effects of thyroid function on HBC risk.
  • To investigate potential mediation effects of metabolic syndrome and waist circumference in the relationship between thyroid function and BTC.

Main Methods:

  • Employed Mendelian randomization (MR) using single nucleotide polymorphisms (SNPs) as instrumental variables.
  • Analyzed data from the ThyroidOmic and FinnGen consortiums.
  • Included univariable and multivariable MR analyses, followed by mediation analysis for thyroid function indicators (FT4, TSH, hyperthyroidism, hypothyroidism) and HBC.

Main Results:

  • Elevated free thyroxine (FT4) levels showed a significant causal association with reduced BTC risk, but not HCC.
  • Thyroid stimulating hormone (TSH), hyperthyroidism, and hypothyroidism did not demonstrate causal associations with HBC risk.
  • The protective effect of FT4 within the reference range (FT4-RR) against BTC was partially mediated by a decreased risk of metabolic syndrome (MetS) and reduced waist circumference (WC).

Conclusions:

  • Higher FT4-RR may offer a protective effect against BTC, with MetS and WC acting as partial mediators.
  • This research underscores the potential role of FT4 in BTC pathogenesis and identifies MetS and WC as significant mediating factors.
Abstract

Keywords:
Mendelian randomizationfree thyroxinehepatobiliary cancermetabolic syndromethyroid functionwaist circumference

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