In the constant search for better approaches to treat and ultimately prevent prostate cancer, it is essential that we better understand the underlying etiology of prostate cancer. In times like this, I am often discouraged by the common mantra that the only known risk factors for prostate cancer are “age, race, and family history”. Surely, there must be other risk factors. Over time, certain risk factors have revealed themselves – obesity (aggressive prostate cancer), diet (likely, but exact details still evolving), and smoking (aggressive prostate cancer) to mention a few. One common factor, but certainly not the only factor, linking obesity, diet, and smoking is they all increase inflammation. If true that increased inflammation drives more prostate cancer, then it begs the question of whether other conditions that are clearly inflammatory-related are linked with prostate cancer. With this background in mind, Ge and colleagues tested the association between inflammatory bowel disease (IBD) and prostate cancer risk.
Ge et al performed a meta-analysis that first identified 416 potential studies. However, after a detailed review, the authors were left with only 9 relevant papers for their meta-analysis, limiting the strength of any conclusions that could be drawn. Nonetheless, these 9 papers included over 86,000 men in cohort studies and over 320,000 men from case-control studies (>22,000 IBD cases and >300,000 IBD-free controls). Most studies were from Europe (n=5) or the United States (US) (n=2) indicating a predominance of white men being studied. The 2 Asian studies combined had ~12,000 men (~3% of all men included in the meta-analysis). In cohort studies, which are generally considered a higher-level of evidence, IBD was associated with a 33% increased risk of prostate cancer. Associations were slightly stronger for Ulcerative Colitis (58% increased risk) than Crohn’s Disease (12% increased risk). In case-control studies, IBD was associated with an 81% increased risk of prostate cancer. Unfortunately, there were too few case-control studies to examine Ulcerative Colitis and Crohn’s Disease separately. In a sensitivity analysis, results were similar with no significant publication bias suggesting the results were robust and not driven by a single publication.
Given that association does not mean causation, we must first think of non-biological reasons why IBD may be linked with prostate cancer. IBD is associated with severe gastrointestinal symptoms and involves frequent examinations and endoscopy. Perhaps these frequent evaluations of the rectum lead to earlier detection of prostate cancer and not actually causes prostate cancer. Alternatively, perhaps the IBD-related inflammation affects the prostate leading to prostate inflammation and elevated PSA leading to biopsies to detect prostate cancer. In short, whether IBD biologically drives prostate cancer growth or merely prostate cancer detection is unknown. Studying IBD and aggressive or fatal prostate cancer may give greater insight into this question.
Nonetheless, there are several mechanisms to suggest the link between IBD and prostate cancer may be driven by more than detection bias. First, IBD is a pro-inflammatory condition. Thus, these men may be more prone to pro-inflammatory conditions and prostate cancer has for decades been linked with greater inflammation. Alternatively, the anti-inflammatory treatments used to manage IBD may impair immune surveillance functions and allowing extant cancers to grow. (side bar….yes, I realize this is arguing that “inflammation” can both cause and prevent cancer – such is the duality of inflammation). While these hypotheses are not novel (i.e. inflammation and prostate cancer has been studied for decades), the more intriguing possibility is that IBD alters the gut microbiome and this in turn influences prostate cancer risk. Exactly how an altered gut microbiome may influence prostate cancer risk is not entirely clear, but certainly given the results of this meta-analysis require further study.
In summary, these results suggest a significant and novel link between IBD and prostate cancer. Whether this due to detection bias, shared etiology, the results of IBD treatments, or IBD influencing pathways that then alter prostate cancer risk requires further study. Hopefully, when this is all sorted out, we will not only have a better idea of the etiology of prostate cancer but this in time can lead to new prevention or treatment strategies. Indeed, this study is one of many that is moving us beyond the age-old adage that the only risk factors for prostate cancer are “age, race, and family history”.
Written by: Stephen J. Freedland, MD, Director of the Center for Integrated Research in Cancer and Lifestyle, Co-director of the Cancer Genetics and Prevention Program, Associate Director for Faculty Development, Faculty Physician, Department of Urology, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA
Read the Full-Text Article: The Association Between Inflammatory Bowel Disease and Prostate Cancer Risk
1. Ge Y, Shi Q, Yao W, Cheng Y, Ma G. The association between inflammatory bowel disease and prostate cancer risk: a meta-analysis. Prostate Cancer Prostatic Dis. 2020;23(1):53-58.