Risk of Developing Colorectal Cancer and Benign Colorectal Neoplasm in Patients With Chronic Constipation

Guérin; R. Mody; B. Fok; K. L. Lasch; Z. Zhou; E. Q. Wu; W. Zhou; N. J. Talley

Disclosures

Aliment Pharmacol Ther 

In This Article

Abstract and Introduction

Abstract

Background. Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).

Aim. To investigate the association between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm (BCN) among severity-stratified patients with and without CC.

Methods. Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC-free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre-index CRCancer- and BCN-free patients, incidence rate ratios (IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC-related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls.

Results. Chronic constipation (N = 28 854) and CC-free (N = 86 562) patients had mean age 61.9 years; 66.7% were female. One-year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC-free patients, respectively. Adjusted IRRs between CC and CC-free patients were 1.59 [95% confidence interval (CI): 1.43–1.78] and 2.60 [95% CI: 1.51–2.70] for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥2 and ≥5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients.

Conclusions. Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation-free patients. These risks increase with the severity of chronic constipation.

Introduction

Chronic constipation (CC) is a major health problem. The worldwide prevalence of constipation is estimated to be 14%[1] (rising to 25% in those over age 65 years[2]), and women are more often affected.[1] Constipation is one of the most prevalent conditions seen in primary care practice and is among the most common indications in the United States for a referral to a gastroenterologist.[3] Colorectal cancer (CRCancer) is the second most common cause of cancer-related death in the United States and the seventh most frequent cause of death among industrialised nations.[4] With about two-thirds of the world's cases occurring in developed countries, CRCancer is predominantly a disease of Westernised countries.[5]

It is unclear whether constipation increases the risk of CRCancer. A postulated causal link between constipation and increased CRCancer risk is that longer gut transit times increase the duration of contact between the colonic mucosa and concentrated carcinogens in the lumen, such as bile acids.[6] However, the association between constipation and CRCancer is controversial in the literature.[7] A recent meta-analysis concluded that, while pooled case–control studies reported a positive association, there was significant heterogeneity in the quality of the data and methods of analysis. Prospective cross-sectional surveys and cohort studies reviewed in the meta-analysis did not find CRCancer to be more prevalent in patients with constipation.[8]

Although several studies have investigated the association between CRCancer and constipation using different design and data sources,[9–17] to our knowledge, none of these studies have investigated the association between CC, disease severity, and CRCancer. The present study addresses this question by comparing patients with CC to a CC-free sample using a retrospective claims database with long-term follow-up information.

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