Single Nucleotide Polymorphisms as Biomarkers for Drug Response and
Toxicity in the Management of Colorectal Cancer
Ashok Varma, Mathaiyan Jayanthi
*
and Deepak Gopal Shewade
Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India
*
Corresponding author: Mathaiyan Jayanthi, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India, Tel: 9442395291; E-mail:
mailjayanthi@gmail.com
Received date: April 16, 2018; Accepted date: May 07, 2018; Published date: May 17, 2018
Copyright: © 2018 Varma A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The current methods of cancer treatment don’t focus on the influence of interpatient genetic variations on the
treatment outcomes. Genetic variations in the genes which are involved with drug metabolism and targets can affect
treatment response and toxicity. In the recent time, many advances have been made to detect such candidate gene
variations and use them as biomarkers in predicting the treatment outcomes in colorectal cancer (CRC). CRC
remains one of the common causes of worldwide morbidity and mortality. In the last decade, many drugs have been
approved including targeted therapies for the management of CRC which lead to improvement in the median
survival and overall survival rate. However, there are significant variations in the response rate and toxicity among
CRC patients with the current anti-cancer drugs. Interindividual response variations to chemotherapy can be
influenced by several factors among them the genetic factor plays a key role. This emphasizes the need for the new
genetic biomarkers which enable the selection of optimal drugs to benefit the patient care. This review focuses on
single nucleotide polymorphisms which are known to affect the outcome of anticancer drugs used in the
management of colorectal cancer.
Keywords: Nucleotide; Biomarkers; Drug; Toxicity; Colorectal
cancer
Introduction
Colorectal cancer (CRC) also known as bowel cancer, ofen begin as
a small polyp on the inner wall of the colon or rectum. Polyps are
benign and adenomatous in nature. Few of these polyps become
cancerous over time [1]. Early fnding and removing of these polyps
can prevent development of CRC.
CRC is the third most commonly diagnosed cancer and the fourth
leading cause of cancer-related deaths worldwide [2]. Incidence rates
of CRC are similar in both the sexes, with a slight male predominance.
As per globacon report 2012, CRC is the third most commonly seen
cancer in men (10% of the total cancers) and second most in women
(9.2% of total cancer). In India as per the Indian Council of Medical
Research (ICMR) consensus document on management of colorectal
cancer released in 2014, the annual incidence rates (AARs) for colon
and rectal cancer in men and women are 4.4 and 3.9 per 100000
respectively [3].
Survival rate with CRC is highly dependent upon the disease stage
at the time of diagnosis. In Asian countries, the overall cure rate has
not been improved in spite of several improvements in CRC
management. Te fve-year survival rate remains 60% in Asian
countries. Te highest survival rates were found in China (60.8%), the
lowest rate was reported in India (31.2%). In the United States, the 5-
year survival rate of CRC is of 64%. Te failure to diagnose in early
stages due to lack of regular screening is the main reason for low
survival rates in Asian countries (Table 1) [4].
Drug Metabolism Drug targets
5-flurouracil & Capecitabine Dihydropyrimidine dehydrogenase Thymidylate synthase
Oxaliplatin Glutathione S transferase DNA adducts
Irinotecan UDP-glucuronosyl transferase Topoisomerase
Cetuximab Reticuloendothelial system Epidermal growth factor receptor
Panitumumab Reticuloendothelial system Epidermal growth factor receptor
Bevacizumab Reticuloendothelial system Vascular endothelial growth factor A
Table 1: Te table shows the current drugs used in CRC management, Respective metabolizing pathways and Drug targets.
Te efcacy of drugs used in the management of CRC is ofen
limited by signifcant interindividual variation. Such variations are
ofen linked to single nucleotide polymorphisms either in the drug-
metabolizing enzymes, DNA repair enzymes or in drug targets [5].
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ISSN: 2153-0645
Journal of Pharmacogenomics &
Pharmacoproteomics
Varma et al., J Pharmacogenomics
Pharmacoproteomics 2018, 9:2
DOI: 10.4172/2153-0645.1000178
Review Article Open Access
J Pharmacogenomics Pharmacoproteomics, an open access journal
ISSN: 2153-0645
Volume 9 • Issue 2 • 1000178