Modifiable pathways for colorectal cancer: a mendelian randomisation analysis

Area of Science:

• Genetics
• Epidemiology
• Oncology

Background:

• Colorectal cancer (CRC) risk is influenced by various factors, but specific modifiable contributors remain unclear.
• Previous epidemiological studies suggest links between lifestyle, cardiometabolic, reproductive, developmental, and inflammatory factors and CRC risk.
• This study aimed to clarify the relationship between potentially modifiable risk factors and CRC.

Purpose of the Study:

• To examine the association between 39 potentially modifiable risk factors and colorectal cancer risk.
• To identify specific lifestyle, obesity, and cardiometabolic factors influencing CRC development.
• To provide evidence for public health policy regarding CRC primary prevention.

Main Methods:

• Utilized a two-sample Mendelian randomization approach with a random-effects model.
• Analyzed data from 26,397 CRC cases and 41,481 controls of European ancestry.
• Employed genetic variants as instrumental variables to mitigate confounding and reverse causation bias.

Main Results:

• No factors showed statistically significant association with CRC risk after multiple testing correction.
• Suggestive associations indicated increased CRC risk with higher body fat percentage, body-mass index, waist circumference, basal metabolic rate, LDL cholesterol, total cholesterol, serum iron, and adult height.
• Low blood selenium concentration and plasma interleukin-6 receptor subunit α showed suggestive associations with decreased CRC risk.

Conclusions:

• Identified several modifiable targets for colorectal cancer primary prevention, including lifestyle, obesity, and cardiometabolic factors.
• Findings suggest that interventions targeting these factors could inform public health policy for CRC prevention.
• Further research is warranted to confirm these suggestive associations and elucidate underlying mechanisms.