Screening for colorectal cancer detects unrecognized disease

Test, episode, and program sensitivities of screening for colorectal cancer as a public health policy in Finland BMJ Online

21 nov 2008--Screening for colorectal cancer detects four out of ten cancers and should be carefully designed to be more effective, according to a study published today on bmj.com.

About one in 20 people in the UK develop bowel cancer during their lifetime. It is the third most common cancer in the UK and the second leading cause of cancer deaths in Europe and the US.

Previous screening trials have show that faecal occult blood testing can reduce the risk of dying by about 16%. More than 50 countries have introduced screening programmes, but their effectiveness in a public health setting is not clear.

Dr Nea Malila and colleagues from the Finnish Cancer Registry examined whether Finland's national colorectal cancer screening programme could detect unrecognised disease. They studied 106 000 people aged 60󈞬 to test how sensitive screening was in identifying unrecognised disease at three levels—the faecal occult blood test (test to detect small traces of blood in faeces that may indicate disease at an early stage), screening episode, and the national screening programme.

A national screening programme for colorectal cancer began in Finland in 2004 as a public health policy in 22 volunteer municipalities and grew to 161 municipalities by 2006.

Nationally it was decided to split the 106 000 people into two groups—a screening group which received faecal occult blood tests kits by mail and a control group which received the routine health services available in the country.

Anyone whose test indicated blood was contacted so a full colonoscopy could take place.

The researchers found that the sensitivity (accuracy) of the test was 55% when considering cancers that developed after positive tests. The sensitivity from screening episodes was 51% and sensitivity was 38% for the national screening programme.

Roughly, four out of ten colorectal cancers were detected thanks to the organised colorectal cancer screening programme and the researchers concluded that the sensitivity of the Finnish programme was "adequate if relatively low".

The study also presents a model of how to implement a new programme using the principles of experimental design to provide good evidence on effectiveness.

The researchers say: "The sensitivity of the Finnish screening programme for colorectal cancer at the first round was adequate even if relatively low. Programme sensitivity in Finland was sufficient to justify continuation of the programme."

In an accompanying editorial, Joan Austoker and Paul Hewitson from the University of Oxford, say that in addition to programme sensitivity there are other important factors that should be taken into consideration when evaluating a cancer screening programme.

Calcium may only protect against colorectal cancer in presence of magnesium

18 nov 2008--High magnesium intake has been associated with low risk of colorectal cancer. Americans have similar average magnesium intake as East Asian populations. If that were all that were involved, observers might expect both groups to have similar risk for colorectal cancer.

However, the United States has seen a much higher colorectal cancer incidence rate than East Asian populations. Furthermore, when East Asians immigrated to the United States, their incidence rates for colorectal cancer increased. This led researchers at Vanderbilt University to suspect there was something else at work.

Calcium supplementation has been shown to inhibit colorectal carcinogenesis although high calcium may simultaneously be preventing the body from absorbing magnesium. United States patients have a higher calcium intake and higher colorectal cancer incidence. "If calcium levels were involved alone, you'd expect the opposite direction. There may be something about these two factors combined – the ratio of one to the other – that might be at play", said Qi Dai, M.D., Ph.D., assistant professor of medicine at Vanderbilt University.

Dai and colleagues examined this hypothesis in a large clinical trial and found indeed that supplementation of calcium only reduced the risk of adenoma recurrence if the ratio of calcium to magnesium was low and remained low during treatment. "The risk of colorectal cancer adenoma recurrence was reduced by 32 percent among those with baseline calcium to magnesium ratio below the median in comparison to no reduction for those above the median," said Qi.

The implications for prevention of adenoma recurrence or reduced risk of primary colorectal cancer is that designing a personalized diet/supplementation regimen that takes the ratio of both nutrients into account may be better than supplementing with one or the other alone.

About one in eighteen individuals will develop colorectal cancer in their lifetime and 40 percent will die within five years of diagnosis, mainly due to diagnosis at a late stage. The understanding of how dietary factors affect colorectal cancer may lead to the prevention of cancer recurrence and possibly prevention of the initial cancer.

A new diagnostic tool for colorectal cancers prognosis

20 sept 2008--To analyze the clinical significance of BAMBI, authors studied its expression in CRC using immunohistochemical staining. They show that BAMBI overexpression is correlated with aggressive tumor phenotypes and predicts tumor recurrence and cancer-related death in CRC. BAMBI may be usable as a target for diagnostic and antibody medicine.
A research article to be published on August 21, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Ohwada S from department of surgery, graduate school of medicine, Gunma University used BAMBI antibody, which is a transmembrane glycoprotein induced by BMP signaling that is related to TGF-β-type I receptors. BAMBI inhibits TGF-β signaling by forming a heterodimer with TGF-β-type II receptors. Previously, authors found that both Wnt/β-catenin signaling and TGF-β signaling activate transcription of BAMBI and that BAMBI expression is aberrantly elevated in most colorectal cancers. To analyze the clinical significance of BAMBI, they studied its expression in CRC using immunohistochemical staining.
BAMBI overexpression is correlated with aggressive tumor phenotypes and predicts tumor recurrence and cancer-related death in CRC. BAMBI may be usable as a target for diagnostic and antibody medicine.
The expression level of BAMBI plays an important role in the pathogenesis of colorectal cancer. The development of a new active monoclonal anti-BAMBI antibody may offer a great improvement in survival of CRC patients and might also serve as a diagnostic tool for CRC prognosis. This is an extremely well written and researched paper. It discovers yet another marker of prognosis for colorectal carcinoma.
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Reference: Togo N, Ohwada S, Sakurai S, Toya H, Sakamoto I, Yamada T, Nakano T, Muroya K, Takeyoshi I, Nakajima T, Sekiya T, Yamazumi Y, Nakamura T, Akiyama T. Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer. World J Gastroenterol 2008; 14(31): 4880-4888
http://www.wjgnet.com/1007-9327/14/4880.asp
Correspondence to: Susumu Ohwada, Department of Surgery, Graduate School of Medicine, Gunma University,3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. go.go.ohwada@gmail.com
Telephone: +81-279-233030 Fax: +81-279-232740