Is bowel habit linked to colorectal cancer? – Results from the EPIC-Norfolk study
Introduction
Colorectal cancer (CRC) is the third most common cancer worldwide after lung and breast cancer in 2002 and the second most common incident form of cancer in Europe in 2004 (376,400 cases, 13% of all incident cases).1, 2 Around 100 new cases of CRC are diagnosed each day in the United Kingdom (UK) in 2006, being the second most common cause of death from cancer in the country.3
Constipation and infrequent bowel movement have long been suggested to be risk factors for colorectal cancer (CRC). In the early 1970s, Burkitt and colleagues hypothesised that bowel flora convert bowel contents to carcinogens or co-carcinogens by a time-dependent process.4, 5 They suggested that low bowel movement frequency from low fibre intake slows intestinal transit thereby prolonging mucosal contact with putative carcinogens in the colonic lumen. However, only a few studies have examined this hypothesis in relation to CRC risk despite its biological plausibility, and prospective studies investigating bowel habit are particularly sparse.
In 1993, a meta-analysis summarised results of nine published case-control studies examining bowel habit and demonstrated a statistically significant increased risk of CRC with constipation or infrequent bowel movement (odds ratio (OR), 1.48; 95% confidence interval (CI), 1.32–1.66).6 However, the individual case-control studies were relatively inconsistent in defining constipation or infrequent bowel movement. In addition, two recent large prospective studies which showed null or negative associations between infrequent bowel movement and the risk of CRC do not agree with the finding from the meta-analysis.7, 8
Conversely, it has also been postulated that intestinal hurry may be a risk factor for CRC having an irritant action on the mucosa of the large bowel, resulting in hyperplasia, dysplasia and neoplasia.9 To date, however, only three case-control studies10, 11, 12 and two prospective studies8, 13 assessed this hypothesis and provided equivocal evidence on the association of loose stools or frequent bowel movement and CRC risk.
Studies often fail to support an association between laxative use and CRC risk7, 12, 14, 15 although commercial laxative use is widely spread, and the uncontrolled long-term abuse of self-administered laxatives may have a harmful effect and may therefore cause several health problems.16
Overall, previous epidemiologic studies, mostly case-control studies, which examined bowel habit in relation to the development of CRC thus far have failed to support conclusively any of the proposed hypotheses. One of the possible explanations of these discrepancies may be that constipation and diarrhoea are common symptoms of CRC, and the relevant time period when risk factors act in the process of cancer development is often unknown.7
The aim of this nested case-control study was to investigate the prospective association between bowel habit, including bowel movement frequency, consistency, quantity, feeling of discomfort during bowel movement, laxative use and risk of CRC in participants of the UK-Norfolk cohort of the European Prospective Investigation Into Cancer and Nutrition (EPIC-Norfolk) study.
Section snippets
Study population
The EPIC-Norfolk Study is an ongoing prospective study of 25,663 men and women aged between 45 and 79 years who were residing in Norfolk, United Kingdom, and were recruited from general practice registers. The design and study methods have been described previously.17 The study was approved by the Norwich Ethics Committee, and participants gave signed informed consent.
Case ascertainment and control selection
Incident CRC cases (International Statistical Classification of Diseases and Related Health Problems (ICD) 9th revision,
Results
During 12 years of follow-up, 159 cases with no history of CRC at baseline provided information on bowel habit and were therefore included in the analyses. Cases and controls were similar with respect to baseline characteristics such as weight, height, WHR, BMI and the distribution of smoking status, HRT use and physical activity (Table 1). Cases reported less energy, dietary fibre and total meat intake. However, none of these differences was statistically significant.
The proportion of cases
Discussion
To our knowledge, this is the first prospective study using a nested case-control design that has reported a significant association between bowel movement consistency and CRC risk. In particular, having loose stools appeared to be a strong risk factor for incident CRC, especially for colon cancer, with an approximately 3-fold increased risk, and this was not substantially changed by adjusting for potential confounding factors or excluding the first three years of follow-up. Two recent Japanese
Conflict of interest statement
None declared.
Acknowledgements
We thank all the participants and the entire EPIC-Norfolk team. EPIC-Norfolk is supported by research programme grant funding from the Cancer Research UK and Medical Research Council with additional support from the Stroke Association and Research into Ageing.
References (29)
- et al.
Cancer incidence and mortality in Europe, 2004
Ann Oncol
(2005) - et al.
Bowel movement, state of stool, and subsequent risk for colorectal cancer: the Japan Public Health Center-Based Prospective Study
Ann Epidemiol
(2006) - et al.
Constipation, laxative use, and colon cancer in a North Carolina population
Am J Gastroenterol
(2003) - et al.
Constipation, laxative use and risk of colorectal cancer: the Miyagi Cohort Study
Eur J Cancer
(2004) - et al.
Symptoms of carcinoma of the colon and rectum
Lancet
(1968) - et al.
Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study
Lancet
(2003) - Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002, Cancer incidence, mortality and prevalence worldwide, IARC CancerBase...
- Cancer Research UK. CancerStats Key Facts on Bowel Cancer. <http:/info.cancerresearchuk.org/cancerstats/types/bowel/>;...
Epidemiology of cancer of the colon and rectum
Cancer
(1971)- et al.
Effect of dietary fibre on stools and the transit-times, and its role in the causation of disease
Lancet
(1972)