Abstract 486P
Background
Colorectal cancer (CRC) is one of the leading causes of mortality from cancer. Cetuximab is a chimeric antibody inhibiting the epidermal growth receptor (EGFR) and has been demonstrated to be effective to treat CRC. However, there are number of single nucleotide polymorphisms (SNPs) leading to a change in the effectiveness of cetuximab treatment. The aim of this study was to investigate SNPs associated with cetuximab efficiency in a Kazakhstan population.
Methods
Genotyping of 9 SNPs associated with cetuximab efficiency (located in 7 different genes on 5 different chromosomes) was performed by QuantStudio 12K Flex PCR and analysed with Thermo Fisher Scientific Cloud service. Statistical analysis was performed with web source [https://www.snpstats.net/]. Log-additive and codominant inheritance models were used for identifying associations.
Results
243 patients with CRC aged from 24 to 87 (female =110; male = 133) and 71 persons from control group, comparable by age and gender, were analysed. Chi-square criteria for SNPs minor allele frequencies (MAF) were calculated. One polymorphism demonstrated significant results (rs2227983 (G/A)) (P=0.02). For rs2227983, MAF was detected in 44% of the control group and 33% of the CRC group. MAF for rs2227983 in Kazakhstan population is nearest to the Southern Asians (35%), while East Asians demonstrate 52% of MAF in this SNP. The MAF for this polymorphism is 29% in the total population. SIFT and PolyPhen predictive models determined rs2227983 as benign. However, PharmGKB indicates that patients with the AA genotype may have decreased survival when treated with cetuximab when compared to patients with the GG genotype. Rs2227983 is located on Chromosome 7:55161562 in the EGRF gene and is involved in PI3K/AKT signalling, so it would be appropriate to consider its inheritance models. According to log-additive genetic modelling of inheritance we found that rs2227983 had a significant association with cetuximab efficiency (P = 0.016) and showed a highly significant inheritance codominant model with odds ratio (OR) 3.55 (P= 0.018).
Conclusions
One polymorphism (rs2227983) was found to be significantly different between cohorts. In the future, cetuximab efficiency should be further explored in the Kazakhstan population in CRC patients including additional influencing factors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Karaganda Medical University.
Funding
Ministry of Education and Science of the Republic of Kazakhstan (Research project # BR05236771).
Disclosure
All authors have declared no conflicts of interest.