There are differences between men and women: the fatter the men and the thicker the waist of women, the higher the risk of colorectal cancer!

Colorectal cancer (CRC) is one of the most common cancers in adults worldwide.

The International Agency for Research on Cancer (IARC), the American Institute of Cancer Research (AICR) and the World Cancer Research Fund (WCRF) believe that obesity is a possible cause of CRC.
This is mainly based on the positive relationship between fat content and CRC risk in observational epidemiology.
Related.

MAYO CLINIC In addition, limited data from observational studies indicate that weight loss can reduce the risk of CRC in postmenopausal women.

However, it is still unclear whether the risks of men and women are different, and how obesity causes CRC from a biological point of view.

In view of the increasing incidence of obesity and the difficulty of reducing fat, these are important issues that need to be clarified.

Recently, researchers from the University of Bristol in the United Kingdom used a naturally occurring test called Mendelian randomization to use genetic information to better understand the causality of adjustable factors and studied two different measures of obesity-namely Whether body mass index (BMI) and waist-to-hip ratio (WHR) are associated with the risk of CRC in men and women, respectively.

Researchers studied the sex- and site-specific associations between fat and CRC risk, and whether fat-related metabolites can explain the association between fat and CRC.

Using BMI and WHR (N = 806810) for genome-wide association studies of genetic variation, and 123 metabolites (N = 24925) targeted for nuclear magnetic resonance metabolomics as tools.

BMI, WHR and CRC risk (58,221 CRC patients and 67,694 controls registered in the GECCC, CCTS, and CCFR studies) were subjected to gender combination and gender-specific Mendelian randomization (MR).

Multivariate models of BMI and WHR and metabolites, metabolites and CRC, and metabolite categories adjusted for BMI and WHR and CRC were performed gender combined MR.

The purpose and hypothesis of the research.

The purpose of the research is to: (1) use the genetic tools of BMI and WHR to estimate the total impact of fat on the risk of CRC; (2) estimate the mediating effect of fat on the risk of CRC by targeting metabolites of NMR metabolomics.

The results showed that in gender-specific MR analysis, men’s higher BMI was closely related to the increased risk of CRC (HR=1.
23, 95%CI: 1.
08, 1.
38).
For every 4.
2 kg/m2 increase in BMI, the risk of CRC increased by 23% .

In women, for every 5.
2 kg/m2 increase in BMI, the risk of CRC increased by 9%.

Interestingly, the relationship between WHR and CRC risk in women is stronger than that in men.
For every 0.
07 increase in WHR, the risk increases by 5%.

Further analysis of the relationship between BMI and WHR and CRC risk based on two MR samples showed that BMI or WHR were related to 104/123 metabolites, but the positive correlation direction of the fat-CRC relationship was inconsistent.

In the multivariate MR analysis, after adjusting the representative metabolite category, the association between BMI and WHR and CRC did not weaken.
For example, if BMI did not change by 1 unit, the OR of CRC was 1.
12 (95%CI=1.
00, 1.
26).
When adjusting the cholesterol in the low-density lipoprotein particles, this number becomes 1.
11 (95% CI=0.
99, 1.
26).

The results show that the higher the male BMI, the greater the female WHR, and the higher the risk of CRC.

Obesity is related to many metabolic changes, but these cannot fully explain the association between obesity and CRC.

References: Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.
BMC Medicine (2020) 18:396.
https://doi.
org/10.
1186/s12916-020-01855-9.