Does IBD affect cancer risk?

By Pooja Toshniwal PahariaApr 3 2024Reviewed by Benedette Cuffari, M.Sc.

In a recent study published in BMC Medicine, researchers explore the causal associations between inflammatory bowel disease (IBD) and cancer incidence.

Study: Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations. Image Credit: Sebastian Kaulitzki / Shutterstock.com

Background

Increasing scientific research indicates that the diagnosis of various types of cancer among individuals 50 years of age and younger is rising worldwide. Therefore, recognizing risk factors among young individuals is critical for avoiding early-stage tumors.

IBD, including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic and progressive gastrointestinal disease that is more frequently associated with certain cancer risks. However, these findings have been contradictory and are potentially influenced by reverse causation and confounding factors. The possible causal links between IBD and cancer incidence remain poorly understood.

About the study

In the present study, researchers used European and East Asian summary genome-wide association study (GWAS) data for genome-wide linkage disequilibrium score regression (LDSC), MR, and colocalization analyses to investigate whether IBD is causally associated with cancer risk. Sensitivity analyses were also conducted to examine the robustness of the primary findings.

The primary analysis involved the random-effects inverse-variance weighted (IVW) approach. Sensitivity analyses included weighted median (WM), penalized weighted median (PWM), MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (RAPS).

The researchers eliminated single-nucleotide polymorphisms (SNPs) associated with confounding factors like waist circumference, hip circumference, body mass index (BMI), waist-hip ratio, percentage of body fat, alcohol consumption, smoking, depression, insomnia, and physical exercise in the multivariate MR (MVMR) analysis to identify significant MR findings.

A meta-GWAS investigation of East Asians and Europeans was performed with a focus on certain malignancies, including esophagus, colorectal, stomach, cervical, liver cell, lung, breast, and prostate cancers. A total of 27 site-specific cancers among Europeans were selected, which included oropharyngeal, stomach, esophageal, colorectal, small bowel, liver, anus, bile duct, pancreatic, liver cell, multiple myeloma, leukemia, nonmelanoma skin, skin melanoma, squamous cell, bladder, kidney, cervical, prostate, ovarian, corpus uteri, breast, lung, brain, and thyroid cancers.

The meta-GWAS among East Asians comprised 14,393 IBD patients with 15,456 non-IBD individuals, 7,372 CD patients with 14,946 control individuals, and 6,862 UC patients with 15,456 control individuals. Meta-GWAS data for Europeans was obtained for 25,042 IBD patients with 34,915 control individuals, 12,194 CD patients with 28,072 control individuals, and 12,366 UC patients with 33,609 controls.

Data were primarily obtained for Europeans from the United Kingdom Biobank, Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) Groups, the Transdisciplinary Research into Cancer of the Lung (TRICL) of the International Lung Cancer Consortia meta-analysis, and a multiple-trait genetic assessment of over 300,000 European, Australian, and American individuals.

Study findings

In East Asian and European populations, a non-significant association was observed between IBD, CD, UC, and malignancies. Among Europeans, significant correlations were observed between CD and ovarian cancers and UC and nonmelanoma skin cancers, with odds ratios (ORs) of 0.9 and 1.0, respectively.

MR adjusted for pleiotropic instrumental factors identified a significant association between CD and ovarian cancers with an OR of 0.89 and non-significant associations between UC and nonmelanoma skin cancers. MR-PRESSO data indicated possible links between IBB, UC, and squamous cell cancers with ORs of 0.97 each.

An association between CD and colorectal, stomach, liver, and lung cancers was also observed. Colocalization data indicated the absence of shared biological mechanisms between IBD and cancer, with possible biases ranked high from pleiotropy, inconsistent findings with sensitivity analyses, and poor reproducibility.

Conclusions

Hereditary lifetime exposure to IBD is not robustly associated with cancer risk; however, the higher risk of certain cancers may be attributed to IBD diagnosis-related variables, such as patient treatment. Among East Asians, no methodology produced genetic evidence for the correlations with eight prevalent malignancies. Comparatively, among Europeans, there was evidence linking CD to ovarian cancers and UC to nonmelanoma skin cancers.

In the future, better-designed epidemiologic studies are needed to confirm the current study findings.