ABSTRACT
INTRODUCTION: Genetic factors play an important role in the development of gastric cancer (GC), a prevalent malignancy in Central Asia. Recent studies have shown that single-nucleotide polymorphisms (SNPs) in several genes are associated with increased GC risk, indicating that genetic variation contributes to gastric carcinogenesis. Located on chromosome 8q24.2, the prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein related to the cell-proliferation inhibition and cell-death induction activity. SNPs in PSCA gene have been found to be associated with gastric cancer risk in a genome-wide association study, but results were not conclusive. This study aimed to investigate the association between two polymorphic variants of PSCA gene (rs2294008 and rs9297976) and the susceptibility to gastric cancer in Uzbekistan. METHODS: Two hundred sixty eight patients with gastric cancer and a control group of 248 healthy individuals were included in this study. DNA samples isolated from these groups were genotyped using PCR-RFLP method. Comparative analysis of resulting genotypes showed a statistically significant association between CT genotype and gastric cancer (p=0.03, additive model of inheritance, Cochran-Armitage trend test). RESULTS: Comparative analysis of the distribution of genotypes of rs2976392 polymorphism did not show a statistically significant difference; however, analysis of the distribution of the rs2976392 genotypes in a subgroup of young women revealed a statistically significant (p = 0.04, additive model of inheritance, Cochran-Armitage trend test) increase in the incidence of AA (38%) and AG (56%) genotypes in patients with GC, compared to the controls (20% and 40%). CONCLUSION: Our findings support that PSCA rs2294008 and rs9297976 polymorphism may contribute to the susceptibility to gastric cancer. Genotyping of these polymorphisms can potentially be recommended as one of the criteria for identification of high risk groups for gastric cancer development in Uzbekistan.
ABSTRACT
In order to better characterize and understand the mtDNA population genetics of Central Asia, the mtDNA control regions of over 1,500 individuals from Uzbekistan have been sequenced. Although all samples were obtained from individuals residing in Uzbekistan, individuals with direct ancestry from neighboring Central Asian countries are included. Individuals of Uzbek ancestry represent five distinct geographic regions of Uzbekistan: Fergana, Karakalpakstan, Khorezm, Qashkadarya, and Tashkent. Individuals with direct ancestry in nearby countries originate from Kazakhstan, Kyrgyzstan, Russia, Afghanistan, Turkmenistan, and Tajikistan. Our data reinforce the evidence of distinct clinal patterns that have been described among Central Asian populations with classical, mtDNA, and Y-chromosomal markers. Our data also reveal hallmarks of recent demographic events. Despite their current close geographic proximity, the populations with ancestry in neighboring countries show little sign of admixture and retain the primary mtDNA patterns of their source populations. The genetic distances and haplogroup distributions among the ethnic populations are more indicative of a broad east-west cline among their source populations than of their relatively small geographic distances from one another in Uzbekistan. Given the significant mtDNA heterogeneity detected, our results emphasize the need for heightened caution in the forensic interpretation of mtDNA data in regions as historically rich and genetically diverse as Central Asia.
