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Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

ABSTRACT: Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.

SUBMITTER: Jahan N

PROVIDER: S-EPMC10138231 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

Jahan Nusrat N Begum Mobashera M Barek Md Abdul MA Aziz Md Abdul MA Hossen Md Shafiul MS Bhowmik Khokon Kanti KK Akter Tahmina T Islam Md Rabiul MR Abdulabbas Hadi Sajid HS Islam Mohammad Safiqul MS

Genes 20230329 4

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of ...[more]

PMID: 37107577

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Project description:Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating one-carbon metabolism. Polymorphisms within the MTHFR gene have been found to increase the risk of breast cancer in different populations. In this study, we evaluated the association of polymorphisms of the MTHFR gene (rs1801133 and rs1801131) with the risk of breast cancer in the Bangladeshi population. This case‒control study included 202 breast cancer patients and 104 healthy controls. After the organic extraction of DNA, genotyping was performed via the PCR-RFLP method. Sanger sequencing was performed to validate the RFLP data. Statistical analyses were performed to evaluate the associations of the polymorphisms. Different computational tools were used to predict the structural and functional consequences of the SNPs. Our study revealed that the MTHFR gene polymorphism rs1801131 is associated with an increased risk of developing breast cancer (p < 0.001, OR = 3.85, 95% CI = 2.06-7.25 for the AC genotype and p < 0.001, OR = 7.82, 95% CI = 2.69-22.05 for the CC genotype). An association was also observed in the dominant model (AC + CC) (p < 0.001, OR = 4.19, 95% CI = 2.28-7.78). For rs1801131, premenopausal status was significantly associated with breast cancer risk (p < 0.001). For rs1801133, no significant association was found with breast cancer risk (p > 0.05, OR = 1.57, 95% CI = 0.90-2.74 for the CT genotype; p > 0.05, OR = 1.35, 95% CI = 0.36-4.92 for the TT genotype). Computational analyses predicted rs1801131 to be tolerated and rs1801133 to be deleterious. Structural analyses demonstrated no significant changes in protein structure but revealed alterations in neighboring interactions according to both bond distances and angles. In conclusion, rs1801131 but not rs1801133 is significantly associated with breast cancer risk in the Bangladeshi population. Moreover, in silico analyses demonstrated changes in the interaction pattern of polymorphic residues with adjacent amino acids.

Project description:PurposeDRD2 gene is considered one of the most important candidate genes for the schizophrenia (SCZ) development due to its role in dopamine signaling and no genetic association study has been conducted yet on the Bangladeshi SCZ patients. The objective of the present study was to investigate the association of DRD2 genetic polymorphisms (rs4648317, rs4936270, and rs7131056) with SCZ in the Bangladeshi population.Patients and methodsThis case-control study consisted of 101 SCZ patients and 101 controls. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.ResultsThe average ages were 22.15 and 22.09 years in patients and controls, respectively (p > 0.05). CT genotype of rs4936270 showed a significantly higher risk for the development of SCZ compared to CC genotype (OR = 2.0, p = 0.023), whereas no association was found for TT genotype. For the dominant model and T allele, rs4936270 showed a higher risk for the development of SCZ (OR = 2.01, p = 0.020; OR = 1.76, p = 0.021, respectively), while the recessive model had no association with SCZ. A statistically significant (OR = 2.70, p = 0.036) higher risk was found for the AA genotype, but no association was found for GA genotype of rs4648317 SNP compared to GG genotype. In case of dominant and recessive models, rs4648317 showed no association with SCZ. 'A' allele of rs4648317 SNP was found to be significantly associated with the elevated risk of SCZ (OR = 1.50, p = 0.044). No association with SCZ of rs7131056 SNP was found for AC, CC genotypes, dominant, recessive, and allele models. Furthermore, from the haplotyping analysis, we found that CAA and TAA haplotypes of rs4936270, rs7131056 and rs4648317 SNPs are associated with SCZ (χ2 = 8.26, p = 0.004; χ2 = 5.31, p = 0.021, respectively). After Bonferroni correction, the association of SCZ did not withstand with any genotype, allele and haplotype (p < 0.017) except CAA haplotype.ConclusionOur results suggest that DRD2 gene polymorphisms may be associated with the susceptibility of SCZ in the young Bangladeshi population.

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Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

Publications

Evaluation of the Association between <i>FGFR2</i> Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

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