The polymorphisms (rs3213801 and rs5744533) of DNA polymerase kappa gene are not related with glioma risk and prognosis: A case-control study.

DNA polymerase kappa (POLK), one of the specialized Y family DNA polymerases, functions in translesion synthesis and is suggested to be related with cancers. Single nucleotide polymorphisms (SNPs) in specialized DNA polymerases have been demonstrated to be associated with cancer risk. To evaluate the association of two common POLK variants (rs3213801 C>T and rs5744533 C>T) with glioma, we conducted a case-control study and genotyped these two POLK variants in 605 patients and 1300 healthy controls. The association analysis revealed no significant correlations were observed between these two POLK SNPs and glioma risk. However, the POLK rs3213801 CT genotype was found to be higher in older glioma patients (≥40) than in younger patients (P = .026). Compared with patients harboring the CC genotype, the frequencies of POLK rs5744533 CT and CT+TT genotypes were increased in patients with lower World Health Organization (WHO) grade glioma (P = .028, 0.044, respectively). According to Kaplan-Meier analysis and log-rank tests, POLK SNPs were not correlated with either the overall survival or progression-free survival. Nevertheless, multivariate analysis revealed that the age (≥40) could increase the risk of death in glioma patients (P < .05), while gross-total resection and temozolomide treatment were found to play protective roles in glioma prognosis (P < .001, respectively). Overall, our results indicated that POLK variants rs3213801 and rs5744533 are not associated with glioma risk and prognosis. However, these polymorphisms are likely to be associated with certain glioma characteristics, such as age and WHO grade. The age, surgery types, and chemotherapy could be independent prognostic factors in glioma. More studies are required to confirm our findings.

[Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients].

Objective: To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival. Methods: Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs. Results: Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P>0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR=0.87, 95% CI=0.77-0.97, P=0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P<0.05). Conclusion: These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients / 中华肿瘤杂志

Objective@#To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival.@*Methods@#Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs.@*Results@#Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P>0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR=0.87, 95% CI=0.77-0.97, P=0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P<0.05).@*Conclusion@#These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

William Polk Longmire Jr. y los primeros 60 años de la cirugía de puentes aorto-coronarios / William Polk Longmire Jr. and the first 60 years of coronary artery bypass graft surgery

Según datos publicados, en el año 1967 se iniciaron los procedimientos quirúrgicos de construcción de anastomosis para el aporte sanguíneo miocárdico, basados en las operaciones realizadas por el argentino René Gerónimo Avaloró en la Cleveland Clinic. Como muchos otros aspectos de la cirugía cardíaca, este hecho ha estado también ensombrecido por imprecisiones históricas, que no han sido adecuadamente dilucidadas; por lo que no se le ha dado el crédito que merece al hombre que realizó la primera anastomosis entre una arteria mamaria interna y un vaso coronario en humanos: el doctor William Polk Longmire Jr. El baipás coronario empezó a salir de su semilla en las expertas manos de Longmire, en Los Ángeles, quizás en una fría mañana del invierno de 1958; unos años antes de que Favaloro decidiera continuar regándola en la Cleveland Clinic. Sirva este artículo -quizás- como el primero de los merecidos homenajes que recibirá este año, sin dudas, el padre de la cirugía coronaria

According to published data, myocardial revascularization procedures to improve blood supply began in 1967, based on the procedures carried out by the Argentine René Gerónimo Favaloro at the Cleveland Clinic. Like many other aspects of cardiac surgery, this fact has also been overshadowed by historical inaccuracies, which have not been adequately clarified; so that the man who performed the first mammary-coronary anastomosis in humans has not been given the credit: Dr. William Polk Longmire Jr. Possibly, the coronary artery bypass began to spring from the seed in the expert hands of Longmire, in Los Angeles on a cold winter morning in 1958. A few years before Favaloro decided to continue watering it at the Cleveland Clinic. This article will hopefully serve as the first of the well-deserved tributes that the undisputed father of coronary surgery will receive this year

miR-20b downregulates polymerases κ and θ in XP-V tumor cells.

XP-V is a subtype of Xeroderma pigmentosum diseases with typical pigmentation and cancers in sun-exposed regions. The present study investigated the role of microRNA-20b (miR-20b) in the imbalance of polymerase expression levels in XP-V tumor cells. Following software prediction results, certain miRNAs were chosen as candidate regulators for the observed imbalance in polymerases in XP-V tumor cells. Reverse transcription-quantitative polymerase chain reaction and western blot were used to test candidate miRNAs for their ability to reduce the expression of these polymerases. A luciferase reporter assay was used to further verify the western blot results. Polymerases κ and θ were expressed at lower levels in XP-V tumor cells compared to normal control cells. A positive correlation was demonstrated between miR-20b and polymerases κ and θ. It was also demonstrated that a proportion of miRNAs had no effect on polymerases κ and θ, despite the software predicting that these miRNAs would target these two polymerases. Therefore, miR-20b may be responsible for the low expression levels of polymerase κ and θ in XP-V tumor cells, which accelerated mismatch in DNA replication repairing.

Increased dietary cholesterol promotes enhanced mutagenesis in DNA polymerase kappa-deficient mice.

DNA polymerase kappa (Polκ) bypasses planar polycyclic N2-guanine adducts in an error-free manner. Cholesterol derivatives may interact with DNA to form similarly bulky lesions. In accordance, these studies examined whether increased mutagenesis of DNA accompanies hypercholesterolemia in Polk-/- mice. These mice also carried apoE gene knockouts to ensure increased levels of plasma cholesterol following exposure to a high cholesterol diet. The mice carried a reporter transgene (the λ-phage cII gene) for subsequent quantitative analysis of mutagenesis in various tissues. We observed significantly increased mutation frequencies in several organs of apoE-/-Polk-/- mice following a high cholesterol diet, compared to those remaining on a standard diet. Regardless of dietary regime, the mutation frequency in many organs was significantly higher in apoE-/-Polk-/- than in apoE-/-Polk+/+ mice. As expected for polycyclic guanine adducts, the mutations mainly consisted of G:C transversions. The life expectancy of apoE-/-Polk-/- mice maintained on a high cholesterol diet was reduced compared to apoE-/-Polk+/+ mice. Overall, this study demonstrates a role for Polκ in bypass of cholesterol-induced guanine lesions.