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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: CAPOX-toxicities,Predictive-markers,DPYD*9A,DPYD*6,GSTP1 ile105va
- چکیده:
- چکیده انگلیسی: Aim: CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. Patients and Methods: We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. Results: The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. Conclusion: A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker.
- انتشار مقاله: 26-04-1398
- نویسندگان: Ashok Varma K,M Jayanthi,Biswajit Dubashi,D G Shewade
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Hodgkin lymphoma,polymorphisms,DNA Repair,PMAIP1/Noxa,TLR4
- چکیده:
- چکیده انگلیسی:
Background: Single nucleotide polymorphisms (SNPs) in DNA repair and Toll-like receptor (TLR) genes have been reported to be associated with Hodgkin Lymphoma (HL) risk. Since such associations may be ethnicity dependent, polymorphisms in TLR4 rs1554973, Xeroderma pigmentosum C (XPC) rs2228000, rs2228001 and a variant near PMAIP1/Noxa gene rs8093763 were here investigated with regard to HL susceptibility in a south Indian population. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: We conducted a case control study consisting of 200 healthy volunteers and 101 cases with HL. DNA samples were genotyped using real-time PCR. Linkage disequilibrium (LD) analysis between rs2228000 and rs2228001 was performed using HaploView (version 4.2). Results: Among the studied variants, we observed that a variant rs8093763 located near PMAIP1/Noxa gene was associated with HL risk (OR=1.72 and 95% CI=1.004-2.93). The major allele frequencies of XPC (rs2228000 and rs2228001), TLR4 (rs1554973) and PMAIP1/NOXA (rs8093763) variants were 79%, 66%, 67% and 59% respectively. The studied frequencies were significantly different from 1000 genome populations. Conclusion: The results suggest that a variant rs8093763 located near the PMAIP1/Noxa gene may modify risk of HL. We found variation in distribution of polymorphic frequencies between the study population and 1000 genome populations. The results may help identify individual risk of development of HL in our south Indian population.- انتشار مقاله: 14-03-1396
- نویسندگان: Dimpal N Thakkar,Sunitha Kodidela,Sandhiya Selvarajan,Biswajit Dubashi,Steven Dkhar
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Hodgkin lymphoma,polymorphisms,DNA Repair,PMAIP1/Noxa,TLR4
- چکیده:
- چکیده انگلیسی:
Background: Single nucleotide polymorphisms (SNPs) in DNA repair and Toll-like receptor (TLR) genes have been reported to be associated with Hodgkin Lymphoma (HL) risk. Since such associations may be ethnicity dependent, polymorphisms in TLR4 rs1554973, Xeroderma pigmentosum C (XPC) rs2228000, rs2228001 and a variant near PMAIP1/Noxa gene rs8093763 were here investigated with regard to HL susceptibility in a south Indian population. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: We conducted a case control study consisting of 200 healthy volunteers and 101 cases with HL. DNA samples were genotyped using real-time PCR. Linkage disequilibrium (LD) analysis between rs2228000 and rs2228001 was performed using HaploView (version 4.2). Results: Among the studied variants, we observed that a variant rs8093763 located near PMAIP1/Noxa gene was associated with HL risk (OR=1.72 and 95% CI=1.004-2.93). The major allele frequencies of XPC (rs2228000 and rs2228001), TLR4 (rs1554973) and PMAIP1/NOXA (rs8093763) variants were 79%, 66%, 67% and 59% respectively. The studied frequencies were significantly different from 1000 genome populations. Conclusion: The results suggest that a variant rs8093763 located near the PMAIP1/Noxa gene may modify risk of HL. We found variation in distribution of polymorphic frequencies between the study population and 1000 genome populations. The results may help identify individual risk of development of HL in our south Indian population.- انتشار مقاله: 14-03-1396
- نویسندگان: Dimpal N Thakkar,Sunitha Kodidela,Sandhiya Selvarajan,Biswajit Dubashi,Steven Dkhar
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Hodgkin lymphoma,polymorphisms,DNA Repair,PMAIP1/Noxa,TLR4
- چکیده:
- چکیده انگلیسی:
Background: Single nucleotide polymorphisms (SNPs) in DNA repair and Toll-like receptor (TLR) genes have been reported to be associated with Hodgkin Lymphoma (HL) risk. Since such associations may be ethnicity dependent, polymorphisms in TLR4 rs1554973, Xeroderma pigmentosum C (XPC) rs2228000, rs2228001 and a variant near PMAIP1/Noxa gene rs8093763 were here investigated with regard to HL susceptibility in a south Indian population. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: We conducted a case control study consisting of 200 healthy volunteers and 101 cases with HL. DNA samples were genotyped using real-time PCR. Linkage disequilibrium (LD) analysis between rs2228000 and rs2228001 was performed using HaploView (version 4.2). Results: Among the studied variants, we observed that a variant rs8093763 located near PMAIP1/Noxa gene was associated with HL risk (OR=1.72 and 95% CI=1.004-2.93). The major allele frequencies of XPC (rs2228000 and rs2228001), TLR4 (rs1554973) and PMAIP1/NOXA (rs8093763) variants were 79%, 66%, 67% and 59% respectively. The studied frequencies were significantly different from 1000 genome populations. Conclusion: The results suggest that a variant rs8093763 located near the PMAIP1/Noxa gene may modify risk of HL. We found variation in distribution of polymorphic frequencies between the study population and 1000 genome populations. The results may help identify individual risk of development of HL in our south Indian population.- انتشار مقاله: 14-03-1396
- نویسندگان: Dimpal N Thakkar,Sunitha Kodidela,Sandhiya Selvarajan,Biswajit Dubashi,Steven Dkhar
- مشاهده