A pooled analysis of five trials with 20 years of follow up suggests that taking a low dose of aspirin may cut the risk of developing and dying from colon cancer, the second most common cancer in developed countries after lung cancer.

The researchers found that it reduced the incidence of colon cancer by 24 per cent and deaths by 35 per cent.

They said their findings may tip the balance in favor of using aspirin to prevent colon cancer, reported Reuters.

Peter Rothwell, Professor of Clinical Neurology at the University of Oxford, and also of Oxford’s John Radcliffe hospital, both in the UK, and colleagues, presented the findings of their analysis in the 22 October issue of The Lancet.

Colorectal cancer has a lifetime risk of 5%; every year about 1 million people discover they have the disease and 600,000 die from it.

In their analysis, Rothwell and colleagues analyzed five pooled randomized trials that assessed the effect of aspirin on incidence and mortality of colorectal cancer, with particular focus on dose, duration of treatment and tumor site.

Previous studies have already shown that high-dose aspirin (500 mg and more a day) reduces long-term incidence of colorectal cancer, but the risk of adverse effects such as gastro-intestinal bleeding “might limit its potential for long-term prevention”, wrote the authors.

For the study, Rothwell and colleagues followed up five trials (done in the UK, Sweden and Holland) that were primarily interested in the effects of aspirin on cardiovascular outcomes but they were able to track colorectal cancer incidence and deaths through cancer registries and death certificates.

They then pooled individual patient data and analyzed the effect of doses of at least 75 mg daily of aspirin on risk of colorectal cancer over 20 years during and after the trials.

The results showed that:

* In four trials of aspirin versus control (average duration of scheduled treatment was 6 years), 2.8 per cent of over 14,000 patients had colorectal cancer over a median follow-up of 18.3 years.

* Those on aspirin had a 24 per cent reduction in risk of colon cancer (incidence hazard ratio HR = 0.76, 95% confidence interval CI = 0.60 – 0.96, p=0.02) and the risk of death also went down by 35 per cent (0.65, 0.48-0.88, 0.005).

* However, rectal cancer did not show such a drop (0.90,0.06-1.30, 0.58 for incidence and 0.80, 0.50-1.28, 0.35 for mortality).

* Where tumor site data was available, it appeared that aspirin reduced risk of cancer of the proximal colon but not the distal colon.

* The benefit increased with scheduled duration of treatment, such that being on aspirin for 5 years or more reduced the risk of proximal colon cancer by about 70 per cent, and reduced rectal cancer risk.

* There was no benefit increase at doses higher than 75 mg a day.

* In the Dutch trial, that tested different doses, the risk of fatal colorectal cancer was higher on 30 mg a day than 283 mg a day.

The authors concluded that:

“Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer.”

“Benefit was greatest for cancers of the proximal colon, which are not otherwise prevented effectively by screening with sigmoidoscopy or colonoscopy,” they noted.

This news is likely to have a mixed reception. Some doctors may be reluctant to promote the aspirin route as a way to prevent colon cancer because of the associated risks, while others may be attracted by the relatively cheap alternative that the drug offers, especially if they sympathize with patients who wish to avoid the discomfort and embarrassment of invasive tests.

In an accompanying editorial, Drs. Robert Benamouzig and Bernard Uzzan, of Avicenne Hospital in Bobigny, France, said the study had limitations in that cancer was not the primary outcome studied in the trials, and there was not enough data on aspirin-related deaths.

Also, the patients were mostly men with cardiovascular risks, so the findings can’t be generalized to other populations like women and people without those risks.

However, they said the study was very “interesting”, particularly in relation to high-risk patients.

Source:
MedicalNewsToday

Low-Dose Aspirin May Cut Risk Of Developing And Dying From Colon Cancer, Nursing Resource Admin

Tumor budding at the invasive tumor front of colorectal cancer is recognized as an independent prognostic factor significantly related to both lymph node and distant metastasis. Several lines of evidence seem to suggest that tumor buds may, to some extent, represent malignant colorectal cancer stem cells because of their potential for migration and re-differentiation locally and at sites of metastasis. However, phenotypic characterization of cancer stem cells in general is still debated although at least 8 putative stem cell markers have been suggested including CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. Little is known about the potential of these proteins to act as prognostic biomarkers in patients with colorectal cancer and most of these proteins have never before been explored within tumor buds themselves.

A research article published in the World Journal of Gastroenterology addressed this problem. Considering the apparent stem cell-like properties of tumor buds and association of budding with adverse clinical outcomes, the research team led by Dr. Alessandro Lugli performed immunohistochemical staining of 8 putative cancer stem cell markers, namely CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. The expression within tumor buds was evaluated, their frequency of occurrence and their potential prognostic significance in patients with colorectal cancer were determined.

Their findings showed that expression of EpCAM and particularly of ABCG5 within the tumor buds of colorectal cancer are frequent events. Moreover, expression of EpCAM or ABCG5 within tumor buds themselves has the potential to stratify patients with colorectal cancer into prognostic subgroups. This was particularly pronounced for patients with node-negative disease.

The results of this study could have important implications for patients with lymph node-negative colorectal cancer. Stratification of this group of patients could help to identify those likely to have a particularly poor outcome who could perhaps be considered for adjuvant therapy.

The study is characterized technically by an excellent application of immunohistochemistry and provides interesting evidence to aid the understanding of the correlation between cancer stem cell markers at the invasive front of colorectal cancer and prognosis. The findings suggest that EpCAM and ABCG5 in tumor buds may be useful biomarkers of poor outcome in this subgroup of patients. However, further studies are necessary to address the important issue of whether EpCAM- or ABCG5-positive tumor buds indeed represent migrating colorectal cancer stem cells.

Reference

Hostettler I, Zlobec I, Terracciano L, Lugli A. ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients. World J Gastroenterol 2010; 16(6): 732-739 http://www.wjgnet.com/1007-9327/16/732.asp

Correspondence to: Dr. Alessandro Lugli, MD, Institute for Pathology, University Hospital of Basel, Schoenbeinstrasse 40, Basel, CH-4031, Switzerland.

Source:
Jin-Lei Wang
World Journal of Gastroenterology

A New Indicator Of Poor Prognosis In Node-Negative Colorectal Cancer Patients, Nursing Resource Admin