52-year old Jignesh was suffering from weight loss and changes in bowel movement. A similar incident in his brother had already been diagnosed as cancer. Jignesh did not want to take any chances and got a PET scan and an endoscopy mediated biopsy done. Biopsy results came out to be positive for colon cancer and Jignesh consulted Dr Rakshit Shah, consultant surgical oncologist, at the Kailash Cancer Hospital and Research Centre (KCHRC), Goraj, Gujarat. D. Shah reviewed the family history and endoscopy results carefully. Based on the endoscopy results showing the presence of >100 polyps in the colon and the biopsy results, Dr Shah performed a colectomy. In the meantime, because of the family history and the extent of polyps, Dr Shah strongly suspected Jignesh to have Familial Adenomatous Polyposis (FAP).
FAP is an autosomal dominant disorder that is caused due to a mutation in the adenomatous polyposis coli (APC) gene. The APC protein is a tumour suppressor gene and carriers with a mutation in the APC gene resulting in an inactive APC protein are at an almost 100% risk of colon cancer by the age of 40.
To confirm the diagnosis and to test other family members, Dr Shah counselled Jignesh and 26 of his family members to agree to undergo genetic testing. A total of 10 family members carried the mutation in the APC gene. 6 members were diagnosed with polyps, 3 of which were diagnosed with cancer and all 6 immediately underwent prophylactic colectomy. 4 members were younger and did not have polyps as yet. However, they have a strong predisposition of getting polyps and colon cancer later and are advised to undergo regular colonoscopies to monitor the generation of polyps.
Colon cancer can also be triggered due to mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2 or EPCAM gene which results in inactive MSH2 protein. These mutations result in the Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). Patients with Lynch syndrome also have an increased risk of developing colorectal cancer. Aneesh was one such patient who had come to Dr Shah with a relapsed case of colorectal cancer. After genetic testing, he had a mutation in the MLH1 gene. His family members were also counselled and underwent genetic testing. However, of the 13 members tested, only Aneesh and his brother were positive and the remaining family members were relieved to have been tested negative.
As per Dr Shah, some of the major challenges in getting patients to undergo genetic testing is the cost factor or the worry regarding social stigma. For these cases, the testing was done for free by MedGenome Labs, Bangalore. Further, because of the existing family history, these families willingly agreed for the testing.
Once operated, there is no need to undergo further treatment. However, colectomies may result in liquid stools with an increase in frequency of bowel movements per day. While this may not seem very enticing to someone to undergo prophylactic surgery, Dr Shah strongly advocates that “prevention is better than cure.” He advices that in such cases, family history is very important and the entire family should be counselled for genetic testing to ensure adequate surveillance and prophylactic therapy.
Currently, there are no targeted therapies to block the tumour-promoting changes that happen in FAP and Lynch syndrome patients. However, there is some hope that boosting the immune system of individuals after colectomy may prevent or delay the progression to full-blown colon cancer.