US scientists have developed a new online tool for identifying people at risk of the most common form of hereditary colon cancer. The questionnaire, designed by researchers at the Brigham and Women's Hospital and Dana-Faber Cancer Institute, aims to help doctors identify who should be offered genetic testing for the condition. Published in the Journal of the American Medical Association (JAMA), the new quiz is based on a five year study of clinical and genetic data from almost 2,000 patients.
Most cases of colon cancer are not inherited, but a small proportion of patients have hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome. This hereditary form of the disease is caused by a mutation in one of several 'mismatch-repair' genes - such as MLH1 and MSH2 - 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. As well as colon cancer, people who inherit HNPCC are at increased risk of womb and other cancers.
The new questionnaire aims to detect people at risk of harbouring a mutated MLH1 or MSH2 gene, so that they can receive extra screening designed to detect the cancer in its early stages. For some individuals, preventative surgery might also be an option. 'We hope the model, and the ease of accessing it on the Web, will lead to healthcare providers being easily able to identify at-risk patients and result in screening at an early age, said lead author Sapna Syngal, adding 'prevention remains one of our best weapons against colon and other cancers'.
US genetic test firm Myraid Genetics provided anonymised data on 898 patients for the study. The researchers matched up samples that tested positive for HNPCC gene mutations with reports of the patient's medical history. Once they had devised the 22 question model, they then tested it with data from another 1,016 patients. Syngal hopes that the questionnaire, called PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) will be easy enough for individuals who think they may be at risk to use themselves. 'We're hoping that it's an easier way to figure out people's risk', she said, adding 'the criteria that existed before was very complicated, and it was hard to know if you were high-risk or not'.
Another risk prediction model for HNPCC was also published in the same issue of JAMA. Researchers at the Johns Hopkins Bloomberg School of Public Health developed the MMRpro software, which can be downloaded from a website. However, according to Dr Jerald Wishner, director of colon and rectal surgery at Northern Westchester Hospital Center in Mount Kisco, New York, the MMRpro requires collecting so much data that 'there's more potential for inaccuracies', adding 'clearly, more research needs to be done'.