Colorectal cancer (CRC) is the second leading cause of cancer deaths in men and women in the United States. Several genetic and environmental/lifestyle factors are known to influence the risk for CRC. Laxative use is a suspected risk factor, but results from previous studies on the use of these medications and CRC risk have been mixed. New research from Dr. Polly Newcomb’s group in the Division of Public Health Sciences was recently published in the journal Annals of Epidemiology that carefully examined laxative use by type and assessed the association with CRC risk.
The new study, “was done as a follow up to a previous study from the VITAL (VITamins And Lifestyle) cohort which also found that CRC risk varied by laxative type,” said Dr. Jessica Citronberg, former Fred Hutch postdoctoral fellow who led the study. The VITAL study was a prospective study and was one of the first studies with sufficient and detailed data in which the association between laxative use by subtype and CRC risk could be analyzed.
In the new study, Dr. Citronberg and colleagues analyzed data collected from a large epidemiologic study, the multi-site international Colon Cancer Family Registry with 4,930 CRC cases and 4,025 controls. Participants in the study reported exposure to numerous known and suspected risk factors for CRC, including questions related to medication use about two years ago, which for cases was prior to their CRC diagnosis. Participants were asked to indicate whether they used fiber laxatives or nonfiber laxatives on a regular basis, defined as using at least twice a week for a month or longer. Fiber laxatives are 'bulk' forming while nonfiber laxatives include subtypes such as stimulant, lubricative, and saline.
First, the authors determined the laxative use among the cases and controls. The use of nonfiber laxatives was about 2% in CRC cases and 1.0% in controls. Overall, more study participants used fiber-based laxatives, with 4.1% (n=198) of cases and 4.7% (n=190) of controls reported using this type. Users were more likely to be older and women. In logistic regression analyses, the authors assessed whether there was a differential risk for CRC by type of laxative used; these analyses controlled for factors associated with use of laxatives or CRC risk such as age, sex, regular use of nonsteroidal anti-inflammatory drugs, use of postmenopausal hormone therapy, CRC family history, and study center site. The use of nonfiber-based laxatives was associated with a more than two-fold, statistically significant increase in risk for CRC (see figure). In contrast, regular use of fiber-based laxatives was not associated with CRC risk. There were differences in the association when examined according to sex or age.
Dr. Newcomb noted that, “The purgative mechanisms of fiber and nonfiber laxatives are very different—although in practice they may have the same result. Therefore it is not surprising that the association with CRC risk may be very different.” In summarizing the findings, Dr. Citronberg concluded, “While more research needs to be done, there does appear to be building evidence suggesting that the association between laxative use and CRC may differ by laxative type.” In their article, the authors suggest that additional follow-up studies are necessary to confirm the potential role of nonfiber laxatives in increasing risk for CRC. Although the potential mechanism(s) is not known, some in vitro and in vivo studies have demonstrated carcinogenic effects of select compounds in stimulant laxatives. While the body of evidence clearly indicates a differential effect of laxatives on CRC risk, future studies should assess the use of laxative fiber versus nonfiber type as separate exposures.
This research was supported by the National Cancer Institute.
Research reported in the publication is a collaboration between Cancer Consortium members Polly Newcomb and Amanda Phipps.
Citronberg JS, Hardikar S, Phipps A, Figueiredo JC, Newcomb P. 2018. Laxative type in relation to colorectal cancer risk. Annals of Epidemiology. doi: 10.1016/j.annepidem.2018.06.011
Citronberg J, Kantor ED, Potter JD, White E. 2014. A prospective study of bowel movement frequency, constipation, and laxative use on colorectal cancer risk. American Journal of Gastroenterology.