Possible Association Between Genetic Alterations and Colorectal Cancer Prognosis

Possible Association Between Genetic Alterations and Colorectal Cancer Prognosis

colonA team of researchers from the Princess Margaret Cancer Centre, the University of Toronto and Memorial University in Canada conducted a study on the possible association between specific genetic alterations and colorectal cancer prognosis in a cohort of Canadian patients. The study was published in the journal Biomarker Research and is entitled “A genome wide association study on Newfoundland colorectal cancer patients’ survival outcomes.

Colorectal cancer is a common malignancy that usually develops from abnormal growths (polyps) in the inner walls of the large intestine. Screening and polyp removal can prevent the disease. Colorectal cancer is considered the second leading cause of cancer death in the United States. In Canada, the population of the island Newfoundland is known to have the highest incidence rates of colorectal cancer and the lowest cancer survival rates.

The identification of new prognostic markers that can help discriminate cancer patients with different risks of disease outcome is quite important. Many studies have focused on genetic predictors of cancer disease outcome such as single nucleotide polymorphisms (SNPs), which correspond to a genetic change in a single DNA base-pair that may modify the disease’s outcome risk. One method of identifying these potential genetic prognostic markers is genome wide association studies.

Microsatellite instability (MSI) can induce the development of colorectal cancer. MSI results from the impairment of the DNA mismatch repair mechanism that corrects errors in the DNA molecule generated during its replication. Cells without this mechanism are unable to correct genetic errors and create microsatellite fragments of genetic information. Colorectal tumors can be classified as microsatellite stable (MSS), MSI-low and MSI-high, with the latter ones having a better prognosis and being mainly found in colon cancer patients compared to rectal cancer patients.

This study aimed at testing the potential use of SNPs as prognostic markers in colorectal cancer using a genome wide survival association study in 431 Caucasian colorectal cancer patients with either MSS or MSI-low from Newfoundland in Canada. In addition, the potential genetic markers were also evaluated separately in colon cancer and rectal cancer.

Researchers were unable to find a SNP with genome wide significance levels in any of the groups analyzed, hypothesizing that this result might be due to the small number of patients evaluated. A small set of ten genetic markers were, however, identified as having a possible association to MSS/MSI-L, colon or rectal cancer patients. Further studies on these ten SNPs should be conducted in larger-sized cohorts to determine whether they are indeed associated with colorectal cancer prognosis.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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