Multigene analysis in carcinogenesis of Colorectal Cancer.
Research type
Research Study
Full title
Mutational analysis of colorectal polyps and subsequent cancer and implications of certain mutations in carcinogenesis
IRAS ID
151356
Contact name
Jacqueline Jamison
Contact email
Sponsor organisation
Northern Health & Social Care Trust
Research summary
Colorectal cancer (CRC) is the 3rd most common type of cancer in the UK and the 2nd highest cause of cancer mortality, it is usually not detected until it has become large or has spread giving a generally poor prognosis. The most common type is adenocarcinoma, the majority of which arise from polyps (growth in the colon) which have acquired mutations (new damage to DNA) over many years which cause them to grow uncontrollably and eventually become malignant. Currently these mutations have limited clinical application; KRAS mutation analysis is used to predict the response to new treatments.
There may be a use for them in screening for CRC as the current screening techniques are not very reliable at detecting cancer early, although colonoscopy is able to excise polyps that it finds. These polyps are currently only analysed microscopically for signs of malignancy, it is proposed that testing for certain mutations at this stage can help to identify how close to malignancy a polyp is, informing appropriate surveillance and management.
The mutations to be tested in this study will be; KRAS, BRAF and PIK3CA, APC and p53m, these are well documented mutation in the colorectal cancer pathway.
KRAS occurs in 30-40% of CRCs, BRAF is less common but strongly suggests a distinct subtype of CRC and PIK3CA is not as strongly implicated but occurs at the transition to cancer. Testing for these mutations will be carried out using the built-for-purpose Randox KRAS/BRAF/PIK3CA Biochip array on paired polyp and cancer samples to determine if there is; (1) a significant occurrence of the mutations and (2) if mutations in the cancer reflect the mutations in the precursor lesion; to justify a larger, more thorough study to evaluate implementing mutation testing into CRC screening.REC name
London - Stanmore Research Ethics Committee
REC reference
14/LO/0564
Date of REC Opinion
20 Mar 2014
REC opinion
Favourable Opinion