Risk of Colorectal Carcinoma May Predispose to the Genetic Variants of the GST, CYP450, and TP53 Genes Among Nonsmokers in the Saudi Community

Abstract

Purpose 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 ( x 2 Yates = 14.7; P = 0.00013, and x 2 Yates = 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.

Genetic Polymorphisms of Cytochromes P450 in Finno-Permic Populations of Russia

“…Thus, the maximum values of the 462Val variant were found in the indigenous peoples of North and South America (over 70%), as well as in the populations of East Asia (over 30%) and Kazakhstan (28.4%) [ 26 , 27 , 28 , 29 , 30 ]. The lowest values are typical for the population of Africa, Europe, and some populations of Western Asia (0–3%, 2–7% and 5.8–9.5%, respectively) [ 2 , 20 , 24 , 31 , 32 ].…”

Variations in TAP1 and PSMB9 Genes Involved in Antigen Processing and Presentation Increase the Risk of Vitiligo in the Saudi Community

“…Genomic DNA samples were isolated from buccal cells by gently scraping the mucosa using an Oragene.DNA-OGR-575 kit (DNA Genotek Inc., Ottawa, ON, Canada) following some modifications. 52 We implemented TaqMan real-time PCR (Thermo, Applied Biosystems, USA) to genotype individuals for the TAP1 rs1135216ʹ D637G’ (C____531909_20) and PSMB9 rs17587 “R60H” (C___8849004_1_) single nucleotide polymorphisms (SNPs) using a 7500 Fast-Dx Real-Time PCR System (ThermoFisher Scientific, USA) with the transcript accessions and protein IDs NM_000593.5 ( NP_000584.2 ) and NM_002800.4 ( NP_002791.1 ) on GRCH38. The probe sequences were 5`-CCC TGA CAG CTG GCT CCC AGC CTC G[C/T]C TAC CTC TGC AGA GCA AAG GGC CAA-3` for TAP1 rs1135216 and 5`-GAC AAG CTG TCC CCG CTG CAC GAG C[A/G]C ATC TAC TGT GCA CTC TCT GGT TCA-3` for PSMB9 rs17587.…”

Molecular pathology of colorectal cancer

“…The genetic variants that have been found to increase CRC risks in the Saudi population include the ABCC1 C218T, ADIPOQ G276T, CYP1A1wt/*2A, GSTM1, KIR 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1, IL17A rs2275913:GA and AA genotypes, NOTCH3 rs1043994: G>A, PARP1 Lys933Asn and Lys945Asn, PRNCR1 rs1456315: CC genotype, RETN rs1862513 and rs375367, TDG rs4135113, TLR9 rs352139, TNFA rs361525 )G238A(, TP53 rs1042522, TSLP rs10043985, VDR1 ApaI rs797232 and TaqI rs731236, and XRCC1 A399G. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Protective variants that have been found in the Saudi population include ABCB1 G2677T, ADIPOQ T45G, CTNNB1 rs44135385, rs2284396, CYP19A1 rs4774585, rs936308, rs4775936, IL7R rs1053496, LRP6 rs2284396, PARP1 rs8679, SFRP3 rs7775, TDG rs1866074, TLR4 rs10759931 and rs2770150, TLR9 rs187084 and rs352144, VDR1BsmI rs1544410 )Table 2(. 41,[50][51][52][53][54][55][56][57][58][59][60][61] Sporadic CRC.…”