Aarohi Usapkar

What clinical and genetic variables are linked to colorectal cancer?

Started Nov. 21, 2023

Abstract or project description

Colorectal cancer, one of the most commonly diagnosed cancers, is caused by an overgrowth of cells in the colon or rectum. It typically appears as polyps, abnormal growths that develop in the lining of the large intestine. It can occur due to inherited germline mutations or acquired somatic mutations that affect oncogenes or tumor suppressor genes. This leaves the body unable to control tumor growth, resulting in invasive malignancies which are commonly treated with surgery, chemotherapy, and targeted radiation. A small portion of colorectal cancer cases are caused by inherited gene mutations, but their effects on specific genes can be corresponded to various cancerous syndromes, such as familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, or hereditary non-polyposis colon cancer (HNPCC). Other possible causes for acquired mutations include age, diet, and lifestyle factors. There are many major genes associated with colorectal cancer, several of which are explored further later on. These include APC, KRAS, MUTYH, PIK3CA, and ZFHX4. APC and MUTYH are tumor suppressor genes involved in the WNT signaling and base excision repair pathways, respectively. WNT signaling controls cell proliferation and is negatively regulated by APC, while MUTYH repairs oxidative DNA damage during BER. Across several data sets, these genes had high mutation rates, and are known to be associated with classic and attenuated polyposis. KRAS and PIK3CA are considered oncogenes, which promote uncontrolled cell growth and metastasis when mutated. KRAS encodes for a GTPase protein that regulates cell growth, differentiation, and survival. Mutations in PIK3CA lead to overstimulation of the PI3K pathway, which leads to cell overgrowth. On the other hand, ZFHX4 behaves similarly to an oncogene during metastasis, yet it is considered a tumor suppressor gene because of its role in tumor proliferation. Although these genes have lower mutation rates according to the data, they have a strong correlation with survival rates of colorectal cancer patients, similar to the previous tumor suppressor genes.