Genetically predicted thyroid function and risk of colorectal cancer: a bidirectional Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Endocrinology
• Gastroenterology

Background:

• Conflicting observational studies suggest a link between thyroid function and colorectal cancer (CRC).
• Understanding the causal relationship is crucial for developing effective CRC prevention strategies.

Purpose of the Study:

• To investigate the causal relationship between five thyroid-related indexes and CRC using Mendelian randomization.
• To assess the bidirectional effect between thyroid function and CRC.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis was employed.
• Genome-wide association study (GWAS) data for thyroid phenotypes (hyperthyroidism, hypothyroidism, TSH, FT4, BMR) and CRC were utilized.
• Bidirectional MR, stratified analysis, and sensitivity analyses were performed.

Main Results:

• Genetically predicted hyperthyroidism, hypothyroidism, TSH, and FT4 were not causally associated with CRC risk.
• Genetically predicted basal metabolic rate (BMR) was significantly associated with increased CRC risk (OR=1.30, P=0.0029).
• BMR was linked to colon cancer but not rectal cancer; no reverse causation from CRC to thyroid function was observed.

Conclusions:

• This bidirectional MR study suggests a potential causal link between high BMR and increased CRC risk.
• Enhanced screening for high BMR individuals may aid in CRC prevention efforts.