Statin Use and Risk of Colorectal Cancer in a Cohort of Middle-Aged Men in the US
- 125 Downloads
Background: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer.
Objective: To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization.
Methods: We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45–69 years who enrolled in the California Men’s Health Study in 2002–3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders.
Results: During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of ≥5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers.
Conclusion: These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for ≥5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.
KeywordsColorectal Cancer Statin Colorectal Cancer Risk Statin User Colorectal Cancer Case
The California Men’s Health Study (CMHS) was supported in part by funds from the California Cancer Research Program (grant number 99-86883). Drs Flick and Chan were partially funded by the Harvard Pharmacoepidemiology Research and Training Fund. The Fund received unrestricted grants from drug companies. Dr Habel has received research support through contracts with the Kaiser Foundation Research Institute from Merck, Eli Lily, Genomic Health, Takeda, AviaraDx, GenenTech and Roche. None of these industry sponsors had any role in this study; they did not sponsor the research, have any role in its design, data collection, analysis, interpretation or drafting. Drs Flick and Habel were supported in part by National Cancer Institute Grant R01 CA98838.
We would like to acknowledge Shelley M. Enger, PhD (Department of Research & Evaluation, Kaiser Permanente, Pasadena, CA, USA), for her contributions to the CMHS conception, design, questionnaire development and data collection. We would also like to thank Virginia Cantrell, MS, RD (Division of Research, Kaiser Permanente, Oakland, CA, USA), for her assistance in the management and administration of the CMHS. We also acknowledge In-Lu Amy Liu, MS, from the Department of Research and Evaluation, Kaiser Permanente, and Ai-Lin Tsai, MS, MA, and Natalia Udaltsova, PhD, from the Division of Research, Kaiser Permanente, for their programming assistance.
- 1.American Cancer Society. Cancer facts and figures 2007. Atlanta (GA): American Cancer Society, 2007Google Scholar
- 5.Carlberg M, Dricu A, Blegen H, et al. Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface: evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cell growth. J Biol Chem 1996; 271(29): 17453–62PubMedCrossRefGoogle Scholar
- 19.Armitage J, Collins R, Bowman L, et al. The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20 536 high-risk people: a randomised placebo-controlled trial [ISRCTN484 89393]. Heart Protection Study Collaborative Group. BMC Med 2005; 3: 6Google Scholar
- 22.Probstfield JL, Davis BR. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002; 288(23): 2998–3007Google Scholar
- 41.Oehrli MD, Quesenberry Jr CP, Leyden W. Northern California Cancer Registry: 2006 annual report on trends, incidence, and outcomes. Oakland (CA): Kaiser Permanente Northern California Cancer Registry, 2006 NovGoogle Scholar
- 49.Selby JV, Smith DH, Johnson ES, et al. Kaiser Permanente medical care program. In: Strom BL, editor. Pharmacoepidemiology. 4th ed. Chichester: John Wiley & Sons, Ltd, 2005: 241–59Google Scholar