All colon cancer tumours should be screened for genetic mutations associated with an inherited form of the disease, say US researchers. The team, based at the Ohio State Comprehensive Cancer Center, say that colon tumours should be tested after surgery, to identify patients and relatives who might benefit from genetic counselling for hereditary nonpolyposis colon cancer (HNPCC). Individuals found to be at risk of the syndrome could then undergo regular monitoring, say the scientists, who published their findings in the New England Journal of Medicine.
Most cases of colon cancer are not inherited, but a small proportion of patients have HNPCC, also known as Lynch syndrome. This hereditary form of the disease is caused by a mutation in one of several 'mismatch-repair' genes, which make proteins that fix genetic mistakes incurred when cells divide and multiply. The decreased ability of patients with HNPCC to repair such genetic errors increases the likelihood that a particular cell will acquire mutations that make it cancerous. Albert de la Chapelle, who led the current study, said: 'these are particularly bad mutations', adding 'a person who has one of these mutations has an almost 100 percent lifetime risk of cancer'. As well as colon cancer, people who inherit HNPCC are at increased risk of womb and other cancers.
The researchers looked at tumour cells taken from 1066 patients newly diagnosed with colorectal cancer, from six different Ohio hospitals. They tested all the samples for evidence of genetic instability, followed by specific tests for HNPCC gene mutations in tumours suspected of harbouring such changes. The team found that tumours from 23 patients (2.2 per cent) had such mutations, including five from people that did not meet the usual criteria for a diagnosis of HNPCC. The scientists then tested 117 first degree relatives of these 23 individuals, and identified a further 52 people at risk of the disease.
The team are now planning a state screening program for HNPCC gene mutations, before proposing a nation-wide program. 'It is important that people who have this syndrome know they have it because there is a good chance we can prevent cancer from developing or at least detect it early when it is more easily treated', said study first author Heather Hampel. Distinguishing HNPCC from non-inherited forms of colon cancer is also important from a treatment point of view, since HNPCC responds poorly to some chemotherapy drugs.
A commentary accompanying the study, written by Henry Lynch (after whom the disease was named), said the results were intriguing, but raised questions over who would pay for such screening. The preliminary test to detect genetic instability in a colon tumour costs around $300, whereas the test to detect HNPCC gene mutations costs more than $2000, he said. 'Should either test be performed routinely among all patients with colorectal cancer? Probably not', he concluded.