Statins 'may cut bowel cancer risk'

Cholesterol-lowering statin drugs “could more than halve the risk of bowel cancer”, according to the Daily Mail.

Millions of people take statins in a bid to prevent problems such as heart attacks and strokes, but several recent studies have looked at whether they might also cut the risk of cancer. This latest news is based on a study of statin use in people with and without bowel cancer. It looked at use of the drug in a group of 101 bowel cancer patients and 132 people without cancer. It found that statin users had a lower risk of developing bowel cancer, and that higher doses and longer duration of statin use were associated with a greater reduction in the odds of having the disease.

Previous research into the potential effect of statins on bowel cancer have had mixed results. Some studies have suggested that the drugs have a protective effect, and others have found no clear association between statin use and bowel cancer risk. It is important to note that this latest study is small, so its results may be inaccurate. This means the results need to be replicated in much larger samples of people. Also, all patients in this study – with or without cancer – were included because they were undergoing colon examinations for bowel symptoms, so they may not represent the general population.

Nevertheless, this small study adds to the mounting evidence that stains may have an effect in protecting against the development of certain cancers. However, more research is needed to confirm the findings and establish how large this protective effect may be.

 

Where did the story come from?

The study was carried out by researchers from the University of East Anglia and the Norfolk and Norwich University Hospital. It was funded by the Norwich Medical School.
 
The study was published in the peer-reviewed journal Biomed Central Gastroenterology.

This research was covered appropriately by the media, with the Daily Mail reporting that previous studies have found conflicting results and that additional research is needed. The newspaper also reported the possible side effects of statin use.

 

What kind of research was this?

This case-control study examined the association between statin use and bowel cancer. Case-control studies are a useful way of examining some types of association as they recruit and compare two groups of participants who either have or don’t have a particular disease or condition. For example, this study compared the histories of people with bowel cancer to those of similar participants without the condition. This allows researchers to study a relationship without having to recruit a large number of participants and follow them up over a long period.

Case-control studies have weaknesses, however, including relying on participants to accurately recall their past behaviour and exposures, often over many years. This can introduce bias into the results as such recollection can be difficult, particularly if someone is trying to understand why they have developed a condition such as cancer. Overall, the limitations of case-control studies mean they are considered to show only associations between two factors, and not that one factor causes the other.

Arguably, as both statin use and bowel cancer are fairly common among the general population, it would be possible to conduct a cohort study to examine bowel cancer development in a large sample of statin users and non-users. A study of this type would take a large group of participants using statins and follow them over time to see which ones developed cancer. It would then examine differences between the participants that may have contributed to the development of cancer. Alternatively, a carefully controlled randomised controlled trial would be the best way to examine this question, although it would need to be carried out over a long period as bowel cancer can take many years to develop.

As mentioned above, case-control studies cannot prove that a particular exposure (such as statin use) causes a particular outcome (such as a reduction in bowel cancer). They are, however, still a useful way to explore potential relationships, and are often conducted as a way to justify attempting large cohort studies or randomised controlled trials. In short, they provide useful initial data that will need to be corroborated through more intensive types of research.

 

What did the research involve?

The research included people who had undergone a colonoscopy at the Norfolk and Norwich University Hospital between September 2009 and May 2010. All the participants had bowel symptoms which led to them to be referred to the hospital for a diagnostic colonoscopy examination. A colonoscopy involves inserting a long, flexible camera into the bowel to look for abnormalities such as tumours, pre-cancerous cells or damage. The study excluded patients who received a colonoscopy for surveillance of current or previous illnesses (such as inflammatory bowel disease), and symptomless patients who received a precautionary screening colonoscopy because they were considered to be at higher risk of bowel cancer (for example, those with a strong family history of bowel cancer).

Bowel cancer cases were identified based on a positive result during a diagnostic colonoscopy test, and control subjects were drawn from patients who had a negative test result. All the participants completed an interview during which information on statin use was collected. The researchers also collected information on other known risk factors for bowel cancer, which were adjusted for during the statistical analysis.

The researchers compared the percentages of cases and controls who reported taking statins, and determined whether the odds of having bowel cancer changed depending on statin use. They performed further analysis to determine whether or not the dose, duration or type of statin used was associated with differing risk of developing bowel cancer. All analyses were presented as odds ratios (OR). This is an appropriate statistical method to use in case-control studies. Odds ratios compare the odds of an outcome in an exposed group (statin users) with the odds of the same outcome in an unexposed group (non-users).

 

What were the basic results?

The research included 101 patients with bowel cancer and 132 cancer-free controls. There were some differences between the two groups. Cases were more likely to be male, older and to drink more alcohol during the course of a week. Controls were more likely to have diabetes and to have previously used aspirin (some research has linked long-term aspirin use to a reduced risk of bowel cancer. These factors were considered to be potential confounders and were controlled for in the statistical analysis.

The researchers found that previous statin use for at least six months was associated with significantly reduced odds of being diagnosed with bowel cancer (OR 0.43, 95% confidence interval [CI] 0.25 to 0.80).

When the researchers performed subgroup analysis based on the duration of statin use, they found that longer statin use was associated with a greater protective effect:

  • 8 cases and 14 controls had used statins for less than 2 years. There was no significant difference in the odds of a bowel cancer diagnosis between statin users and non-users (OR 0.66, 95% CI 0.21 to 1.69).
  • 7 cases and 23 controls had used statins for 2 to 5 years. There was no significant reduction in odds of bowel cancer diagnosis (OR 0.38, 95% CI 0.14 to 1.01).
  • 5 cases and 31 controls had used statins for over 5 years. This was associated with an 82% reduction in the odds of being diagnosed with the disease (OR 0.18, 95% CI 0.06 to 0.55). This particular association was statistically significant.

When the researchers performed subgroup analysis based on the statin dose, they found larger doses were associated with a greater protective effect:

  • 12 cases and 28 controls used a dose of less than 40mg a day. There was no significant reduction in odds of bowel cancer diagnosis at this dose (OR 0.51, 95% CI 0.21 to 1.24).
  • 8 cases and 40 controls used a dose of 40mg or greater a day. This was associated with an 81% reduction in the odds of being diagnosed with the disease (OR 0.19, 95% CI 0.07 to 0.47).

 

How did the researchers interpret the results?

The researchers concluded that statin use was associated with a reduction in bowel cancer diagnosis, and that this reduction was largest at higher doses and with longer duration of statin use.

 

Conclusion

This study suggests that stains, a commonly prescribed class of cholesterol-lowering drugs, may protect against bowel cancer. However, further research with more participants and a more robust study design will be needed to confirm its findings.

This was a relatively small study, which was further divided during subgroup analysis. Analysing small numbers of participants increases the possibility that any risk associations calculated could be inaccurate. Larger studies are needed to verify the associations found in this research.

The researchers report that one of their study’s strengths is that a comprehensive drug history was available, both through prescription records and patient reports. This increases the likelihood that exposure to statins was correctly classified. Additionally, all the participants underwent the same diagnostic testing to confirm or rule out the presence of bowel cancer.

There were, however, limitations to the study. For instance, all the participants had symptoms that indicated the need for a colonoscopy. Given that the control group may have had health issues relating to their bowels, the results may not reflect the risk of bowel cancer in the wider population. Further studies including participants receiving a screening, rather than diagnostic, colonoscopy could help address this potential bias.

When being used to treat or prevent cardiovascular problems, statin drugs may be given as part of a package of treatments including dietary changes and salt reduction. It’s possible that people with the greatest need for cholesterol-lowering statins may also modify their diet alongside their use of statins. Given that diet is associated with bowel cancer risk, dietary changes (and not just the use of statins) may have played a role in the association. This study did not investigate the participants’ dietary habits; furture studies could be improved by examining this risk factors.

The researchers say that the protective effect seen in their study was greater than that seen in other studies with similar results. They also point out that not all previous research has found a protective effect, and that there are inconsistent findings across the field. They say that these inconsistencies may be due to differences in the populations studied, or the duration of statin use. Given the variability in results, more research is needed before we can be confident that statins are indeed associated with a reduced risk of developing bowel cancer. Ideally, this research should be a prospective cohort study or randomised controlled trial.

Overall, this case-control study adds to the existing evidence that statin use has a potential protective effect on the development of bowel cancer. Further research is needed to confirm the findings, and the risks associated with statin use will need to be weighed up against any benefits before the drugs are considered for cancer-prevention purposes.

Analysis by Bazian

Broughton T, Sington J, Beales ILP. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case- control study. BMC Gastroenterology. Published April 24 2012

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