Molecular Biomarkers for Cancer Chemotherapy in Indian Population

Abstract

A large pool of knowledge about the genetic variants is available; however, the elucidation of the functional effect of these variants on human health and disease still poses a challenge for the scientists. A number of studies have been conducted globally to understand the functional association of genetic variability but due to vast differences in the frequency distribution among different populations, it is warranted that an association study be conducted specific to each population. In this study we evaluated the distribution of the variant alleles in our Indian population and compared it with those observed in the other populations that have been studied. There were significant differences in the distribution of some of the alleles in comparison to other ethnic groups like Chinese, Japanese, Caucasians, Africans and many others. Also an association of genetic variants with the development of head and neck, and breast cancer was evaluated where a significant correlation was observed for some of the variants studied. In case of DPYD, there was a significant correlation between the variants of 85T>C and susceptibility to head and neck cancer (p= 0.006) and breast cancer (p= 0.024); and a significant correlation for variants of IVS14+1G>A and susceptibility to breast cancer (p= 0.021). In case of GSTT1, there was a strong association with susceptibility to head and neck cancer (p= 0.001) and for GSTM1 there was a strong association with susceptibility to head and neck cancer (p= 0.024) and breast cancer (p= 0.018). The variants of CYP2C9 were found to be susceptible to head and neck cancer (p< 0.0001) and breast cancer (p< 0.0001); and variants of CYP2C19 had a significant correlation with susceptibility to breast cancer (p= 0.0006). Cancer therapeutics have a narrow therapeutic index and lead to many adverse reactions in patients. Hence, it is desirable for the patients if it is known prior to drug prescription whether a drug would be effective and/or toxic to that individual based on the genetic profile of that individual. However, an association of the genetic variability and the phenotype in terms of efficacy and/or toxicity needs to be established before these tests can be applied on a routine basis in the clinic. In this X study we aimed to establish such a correlation in the Indian patients suffering from head and neck cancer and prescribed 5-Fluorouracil and Cisplatin; and breast cancer patients prescribed 5-Fluorouracil, Cyclophosphamide and Adriamycin. In case of head and neck cancer patients we observed a significant correlation between variants of Glutathione S-transferase M1 and toxicity to cisplatin (p= 0.043). However, due to unavailability of data on efficacy we could not correlate the genetic variability with the efficacy of the drugs. Also, clinical data for the breast cancer patients in terms of toxicity and efficacy was unavailable and so correlation could not be established in case of breast cancer. This preliminary study should be replicated on larger patient pool and may prove to be a stepping-stone for exploring the applicability of such accompanying genotyping tests in the clinic.