A Mendelian randomization found that a potential link between constipation and colorectal cancer, with support for constipation as a cause of colorectal cancer.
Colorectal cancer (CRC) may be caused by constipation, according to a study published in Frontiers in Oncology, where a Mendelian randomization (MR) found that a potential link existed between the 2 conditions.
Although some scientists have looked into the link between constipation and CRC, previous observational studies have been controversial due to their observational natures. This study aimed to use a MR to evaluate the causal link between CRC risk and constipation, including the effects of constipation on CRC and vice versa.
The researchers used the Open Genome-Wide Association Studies (GWAS) database to collect summary datasets and conducted a 2-sample MR study with the available data. Genetic variants that were linked to constipation and colorectal cancer were used as instrumental variables (IVs), and all IVs were checked to see if they were associated with confounders for the effect of constipation on CRC and CRC on constipation. The primary MR method used was the Inverse Variance Weighted (IVW)-Random Effects.
The study included data for constipation from 218,810 European individuals; colorectal cancer from 377,673 European individuals; colon cancer from 462,933 European individuals; and rectal cancer from 456,276 European individuals.
A total of 26 independent genome-wide single nucleotide polymorphisms (SNPs) were identified in the constipation GWAS. The F statistic, which took into account the effect magnitude and precision on constipation, ranged from 20 to 30, demonstrating strength in the variables. A potential causal link was indicated by the IVW-random effect analysis between constipation and CRC (OR, 1.002; 95% CI, 1.000-1.004). The researchers did not find a causal association in any other IVW approach, nor did they find a causal association of constipation on colon or rectal cancer alone.
Additionally, there was no evidence found of a causal effect of CRC on odds of constipation in the IVW-random effects analysis (OR, 0.137; 95% CI, 0.007-2.824). No other approach was able to find a causal relationship of CRC, colon cancer, or rectal cancer on constipation, and heterogeneity was found to be low in the model.
There were some limitations to this study, including the possibility that the genetic variants picked from the GWAS could influence other pathways besides constipation or CRC. Lifestyle or environmental factors were not accounted for in favor of genetic makeup, and as mentioned by the researchers, future studies should look into dietary habits, physical activity, and the medications used by patients to evaluate other risk factors.
Overall, the researchers concluded that the study provides evidence that constipation could increase the risk of CRC. Being able to manage constipation could help to prevent CRC in the future, making it a key risk factor, and a healthy diet and balanced gut microbiota could help to reduce the risk of CRC in patients who have had constipation in the past.
Reference
Wu L, Wu H, Huang F, et al. Causal association between constipation and risk of colorectal cancer: a bidirectional two-sample Mendelian randomization study. Front Oncol. Published online November 16, 2023. doi:10.3389/fonc.2023.1282066
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