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Implication of alterations in Parkin gene among North Indian patients with colorectal cancer.

ABSTRACT: BACKGROUND/AIMS:Alterations in Parkin (PRKN) have been described in many cancers; however, the molecular mechanism that contributes to loss of Parkin expression in colorectal cancer (CRC) remains unclear. The aim of this study was to investigate the involvement of PRKN mutation and loss of heterozygosity (LOH) in loss of Parkin expression. To understand the role of PRKN in cancer progression, we also evaluated the association of Parkin expression with clinicopathological parameters in North Indian population. MATERIALS AND METHODS:We studied 219 CRC samples and their adjacent normal tissues (control) obtained from North Indian patients with CRC. The expression of Parkin was analyzed by immunohistochemistry (IHC). PRKN mutations were analyzed by single-stranded conformational polymorphism (SSCP) and sequencing. For loss of heterozygosity (LOH), we employed two intragenic, D6S305 and D6S1599, and one telomeric marker, D6S1008. RESULTS:In our study, we found four novel somatic mutations, namely, C166G, K413N, R420P (exon 4), and V425E (exon 11). Both mutation in Parkin (p = 0.0014) and LOH (p = 0.0140) were significantly associated with loss of Parkin expression. Additionally, Parkin mutations were not associated with the clinicopathological parameters of the patients. Furthermore, both, LOH in Parkin and Parkin expression were significantly correlated with different clinicopathological variables (p<0.05). CONCLUSION:Our results indicate that Parkin expression is not regulated by a single mechanism, but both mutation and LOH contribute to loss of Parkin expression. We also provide evidence of involvement of Parkin in metastasis and cancer progression. We, therefore, suggest Parkin as a potential prognostic marker and warrant further analysis in this direction.

SUBMITTER: Tiwari RR

PROVIDER: S-EPMC7197922 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae and mainly affects skin, peripheral nerves. Vitamin D receptor (VDR) gene polymorphism has been found to be associated with leprosy. Vitamin D has been shown to control several host immunomodulating properties through VDR gene. Vitamin D deficiency was also found to be linked to an increased risk for several infections and metabolic diseases.ObjectiveIn the present study, we investigated the association of VDR gene polymorphism, mRNA gene expression of VDR and the vitamin D levels with leprosy and its reactional states.MethodologyA total of 305 leprosy patients consisting of tuberculoid (TT), borderline tuberculoid (BT), borderline lepromatous (BL), lepromatous leprosy (LL), as well as 200 healthy controls were enrolled in the study. We identified single nucleotide polymorphisms (SNPs) of VDR Taq1, Fok1 and Apa1, as well as the expression of VDR mRNA gene using PCR-based restriction fragment length polymorphism (RFLP) analysis and real-time PCR respectively. We also performed ELISA to measure vitamin D levels.ResultWe observed that SNP of VDR gene (Fok1 and Taq1) are associated with the leprosy disease. The allelic frequency distribution of T and t allele (p = 0.0037), F and f allele (p = 0.0024) was significantly higher in leprosy patients and healthy controls. ff genotype of Fok1 was found to be associated with leprosy patients [p = 0.0004; OR (95% CI) 3.148 (1.662-5.965)]. The recessive model of Fok1 genotype was also found to be significantly associated in leprosy patients in comparison to healthy controls [p = 0.00004; OR (95% CI) 2.85 (1.56-5.22)]. Leprosy patients are significantly associated with t-F-a haplotype. Further, VDR gene expression was found to be lower in non-reaction group compared to that of reaction group of leprosy and healthy controls. Paradoxically, we noted no difference in the levels of vitamin D between leprosy patients and healthy controls.ConclusionBlood levels of vitamin D do not play any role in clinical manifestations of any forms of leprosy. ff genotype of Fok1 and tt genotype of Taq1 was found to be associated with leprosy per se. Association of t-F-a haplotype with leprosy was found to be significant and could be used as a genetic marker to identify individuals at high risk for developing leprosy. VDR gene expression was lower in TT/BT and BL/LL groups of leprosy in comparison to that of healthy controls.

Project description:BackgroundCell surface biomarker CD44 plays an important role in breast cancer cell growth, differentiation, invasion, angiogenesis and tumour metastasis. Therefore, we aimed to investigate the role of CD44 gene polymorphisms in breast cancer risk and prognosis in North Indian population.Materials & methodsA total of 258 breast cancer patients and 241 healthy controls were included in the case-control study for risk prediction. According to RECIST, 114 patients who received neo-adjuvant chemotherapy were recruited for the evaluation of breast cancer prognosis. We examined the association of tagging SNP (rs353639) of Hapmap Gujrati Indians in Houston (GIH population) in CD44 gene along with a significant reported SNP (rs13347) in Chinese population by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. In-silico analysis for prediction of functional effects was done using F-SNP and FAST-SNP.ResultsNo significant association of both the genetic variants of the CD44 gene polymorphisms was found with breast cancer risk. On performing univariate analysis with clinicopathological characteristics and treatment response, we found significant association of genotype (CT+TT) of rs13347 polymorphism with earlier age of onset (P = 0.029, OR = 0.037). However, significance was lost in multivariate analysis. For rs353639 polymorphism, significant association was seen with clinical tumour size, both at the genotypic (AC+CC) (P = 0.039, OR = 3.02) as well as the allelic (C) (P = 0.042, OR = 2.87) levels. On performing multivariate analysis, increased significance of variant genotype (P = 0.017, OR = 4.29) and allele (P = 0.025, OR = 3.34) of rs353639 was found with clinical tumour size. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs353639 polymorphism.ConclusionsThese findings suggest that CD44 rs353639 genetic variants may have significant effect in breast cancer prognosis. However, both the polymorphisms- rs13347 and rs353639 had no effect on breast cancer susceptibility.

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Implication of alterations in Parkin gene among North Indian patients with colorectal cancer.

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