Nav: Home

Statins and colorectal cancer

April 26, 2016

Confounding rather than causation may explain association between statin use and lower risk of colorectal cancer

Both statin use and increased cholesterol have been linked to lower risk of colorectal cancer. Some have questioned whether the apparent beneficial effects of statins are due to indication bias, which occurs when the indication (high cholesterol) for the medication under study (statin) is also related to the outcome of interest (colon cancer). A large case-control study published in this week's PLOS Medicine conducted by Ronac Mamtani, MD, MSCE, an assistant professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA, and colleagues provides evidence that indication bias may explain the link between statin use and reduced colorectal cancer risk.

The researchers identified 22,163 patients with colorectal cancer and 86,538 patients without known colorectal cancer from a computerized database of electronic records of >10 million UK patients in primary care practices (The Health Improvement Network [THIN]). They confirmed findings from previous studies that showed a decreased risk of colorectal cancer in statin users compared to non-users (OR, 0.95; 95% CI, 0.91-0.99), however, they found that the difference in the risk of colorectal cancer was not significantly different between those patients who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79-1.22), suggesting that indication bias may explain the findings. Consistent with this observation, increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per 1 mmol/L (~38.6 mg/dl) increase; 95% CI, 0.87-0.91).

Additionally, they observed that decreases in total serum cholesterol by >1 mmol/L at least a year before the cancer diagnosis were associated with 1.25-fold and 2.36-fold increased risk of colorectal cancer in users and nonusers of statins.

Although the researchers adjusted for numerous confounding factors in their analysis, given the observational nature of the study, the findings are limited by the potential for residual confounding by unmeasured factors.

The authors say: "Together, these data demonstrate a complex association between statins, cholesterol, and colorectal cancer, suggesting that unexplained cholesterol lowering in statin users or nonusers may be a marker of undiagnosed colorectal cancer."

They continue, "Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy."
Research Article


This research was supported by the National Institutes of Health (grant number K23-CA187185 to RM, K08-DK095951-02 to FIS, K08-DK098272 to DSG, and K24-DK078228 to JDL). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Competing Interests:

I have read the journal's policy and the authors of this manuscript have the following competing interests: RM reports personal fees from Takeda, outside the submitted work; JDL reports personal fees from Pfizer, Merck, and AstraZeneca, and grants from Shire, Takeda, Bayer, and Nestle Health Science, outside the submitted work; FIS has received research support from Takeda, outside the submitted work; and TA reports personal fees from Roche, outside the submitted work. Pfizer, Merck, AstraZeneca, Takeda, and Bayer are manufacturers of statins. The remaining authors (DSG YXY BB JD) have declared that no competing interests exist.


Mamtani R, Lewis JD, Scott FI, Ahmad T, Goldberg DS, Datta J, et al. (2016) Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study. PLoS Med 13(4): e1002007. doi:10.1371/journal.pmed.1002007

Author Affiliations:

Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Tel-Aviv University, Tel-Aviv, Israel



Ronac Mamtani
Perelman School of Medicine at the University of Pennsylvania
Division of Hematology-Oncology
Abramson Cancer Center
Philadelphia, Pennsylvania 19104


Related Colorectal Cancer Articles:

New method for early screening of colorectal cancer
A highly sensitive method that can detect even the earlier stages of colorectal cancer has been developed by researchers in Japan.
Adults with disabilities screened less often for colorectal cancer
Colorectal cancer is the fourth most common type of cancer in the United States, with nearly 135,000 cases reported in 2016.
Colorectal cancer statistics, 2017
Despite dramatic reductions in overall colorectal cancer incidence and mortality, striking disparities by age, race, and tumor subsite remain
Gene mutations among young patients with colorectal cancer
While many patients with colorectal are diagnosed when they are older than 50, about 10 percent of patients are diagnosed at younger ages.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
New immunotherapy study at Sanford centers on colorectal cancer
Sanford Health has opened another clinical trial exploring the power of the body's immune system to fight cancer.
UA Cancer Center team questions safety, efficacy of selenium and colorectal cancer risk
Selenium has been a popular nutritional supplement for decades, touted for its antioxidant properties and its role in stopping free radicals from damaging cells and DNA.
How mouth microbes may worsen colorectal cancer
Bacteria commonly found in the mouth have been recently shown to worsen colorectal cancer in animals, but it has not been clear how these microbes make their way to the gut in the first place.
Pretargeted radioimmunotherapy may eliminate colorectal cancer
An emerging cancer therapy has colorectal tumors surrounded. Presenters at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging are unveiling a novel radioimmunotherapy that combines a cancer-seeking antibody with potent radionuclide agents, resulting in complete remission of colorectal cancer in mouse models.
As colorectal cancer rate falls, diagnosis of late-stage cancer in young patients is up
University of Colorado Cancer Center study presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2016 finds that in patients over 50, the rate of CRC is falling at 2.5 percent per year while the rate of CRC in patients under 50 is rising at 0.8 percent per year.

Related Colorectal Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...