الوصف: |
Ikhlas A Sindi,1 Ahmed O Babalghith,2 Mohammed T Tayeb,2 Ahmad H Mufti,2 Hind Naffadi,3 Samar N Ekram,2,4 Ezzeldin N Elhawary,5,6 Munaifah Alenezi,2 Nasser A Elhawary2,7 1Department of Biotechnology, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca, 21955, Saudi Arabia; 3Common Science, First Year Deanship, Umm Al-Qura University, Mecca, Saudi Arabia; 4Department of Medical Oncology, King Abdullah City Hospital, Mecca, Saudi Arabia; 5MS Genomic Medicine Program, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK; 6Faculty of Biotechnology, October Modern Sciences and Arts University, Giza, Egypt; 7Department of Genetics, Faculty of Medicine, Ain Shams University, Cairo, EgyptCorrespondence: Nasser A ElhawaryDepartment of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi ArabiaTel +966 55 369 2180Email naelhawary@uqu.edu.saIkhlas A SindiDepartment of Biotechnology, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaEmail easindi@kau.edu.saPurpose: Colorectal carcinoma (CRC) represents a considerable public health burden in Saudi Arabia. Several candidate genes and genetic variants have been associated with morbidity and mortality among patients with CRC. We explored whether allelic variants of the GSTM1, GSTT1, CYP450 (rs4646903 and rs1048943), and TP53 (rs1042522) genes predisposed nonsmoking Saudi individuals to increased risk for CRC.Patients and Methods: DNA from buccal cells of 158 participants (80 with CRC and 78 healthy controls) were analyzed for five SNPs using conventional PCR and TaqMan genotyping assays. The SNPStats software was utilized to choose the best interactive inheritance mode for selected SNPs (https://www.snpstats.net).Results: The mean age of diagnosis was 62.4± 13.5 years (range, 40– 83 years), with those aged 71– 80 years and those aged 40– 50 years accounting for the most diagnoses (35.7% and 28.6% of diagnosis, respectively). The GSTM1 and TP53 rs1042522 SNPs were associated with CRC (OR= 3.7; P< 0.0001, and OR= 1.6; P= 0.033, respectively). A plausible contribution to CRC was observed for the GSTM1 and TP53 rs1042522 SNPs (x2Yates= 14.7; P= 0.00013, and x2Yates= 11.2; P= 0.0008, respectively), while the GSTT1 null variant did not affect risk. Heterozygosity in the CYP450 (rs4646903 and rs1048943 SNPs) was associated with a significant risk for CRC. The GSTM1/GSTT1 and CYP450 rs4646903/rs1048943 SNP pairs were in linkage disequilibrium, and the associations were statistically significant (P= 0.01 and P= 4.6x10‒7, respectively).Conclusion: The GSTM1 and TP53 rs1042522 variants can increase the development of CRC in Saudi nonsmokers. Even the presence of one copy of a variant allele in the CYP1A1 gene can predispose CRC risk. Additional studies should also examine other SNP combinations with lifestyle factors that may help prevent, rather than facilitate, colorectal tumorigenesis.Keywords: colorectal carcinoma, single nucleotide polymorphism, TaqMan genotyping, linkage disequilibrium, age at diagnosis, nonsmokers |