Genetic and epigenetic alterations in MGMT gene and correlation with concomitant chemoradiotherapy (CRT) in cervical cancer.

PURPOSE: The MGMT (O6-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer. METHODS: A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0. RESULTS: Individuals with GG genotype, G allele of rs2308327, and haplotype 'TA' of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25 months significant in comparison to methylated MGMT promoter. CONCLUSION: Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.

Higher order genes interaction in DNA repair and cytokine genes polymorphism and risk to lung cancer in North Indians.

Context: Lung cancer pathological process involves cumulative effects exerted by gene polymorphism(s), epigenetic modifications, and alterations in DNA repair machinery. Further, DNA damage due to oxidative stress, chronic inflammation, and the interplay between genetic and environmental factors is also an etiologic milieu of this malignant disease. Aims: The present study aims to assess the prognostic value of DNA repair, cytokines, and GST gene polymorphism in lung cancer patients who had not received any neoadjuvant therapy. Materials and Methods: In this case-control study, 127 cases and 120 controls were enrolled. DNA from the blood samples of both patients and controls was used to genotype XRCC1Arg399Gln, XPDLys751Gln, and interleukin-1 (IL-1ß) genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas multiplex PCR was performed to genotype GSTT1 and GSTM1. Results: Binary logistic regression analysis showed that XRCC1Arg399Gln-mutant genotype (Gln/Gln, odds ratio [OR] = 4.6, 95% confidence interval [CI]: 2.2-9.6) and GSTT1 null (OR = 2.7, 95% CI: 1.6-4.5) were linked to cancer susceptibility. Generalized multidimensional reduction analysis of higher order gene-gene interaction using cross-validation testing (CVT) accuracy showed that GSTT1 (CVT 0.62, P = 0.001), XPD751 and IL-1ß (CVT 0.6, P = 0.001), and XRCC1399, XPD751, and interleukin-1 receptor antagonists (IL-1RN) (CVT 0.98, P = 0.001) were single-, two-, and three-factor best model predicted, respectively, for lung cancer risk. Classification and regression tree analysis results showed that terminal nodes which contain XRCC1399-mutant genotype (AA) had increased the risk to lung cancer. Conclusion: The present study demonstrated that XRCC1399 (Gln/Gln), GSTT1, and IL-1RN allele I, I/II served as the risk genotypes. These genes could serve as the biomarkers to predict lung cancer risk.

Cytokine gene variants and socio-demographic characteristics as predictors of cervical cancer: A machine learning approach.

Cervical cancer is still one of the most prevalent cancers in women and a significant cause of mortality. Cytokine gene variants and socio-demographic characteristics have been reported as biomarkers for determining the cervical cancer risk in the Indian population. This study was designed to apply a machine learning-based model using these risk factors for better prognosis and prediction of cervical cancer. This study includes the dataset of cytokine gene variants, clinical and socio-demographic characteristics of normal healthy control subjects, and cervical cancer cases. Different risk factors, including demographic details and cytokine gene variants, were analysed using different machine learning approaches. Various statistical parameters were used for evaluating the proposed method. After multi-step data processing and random splitting of the dataset, machine learning methods were applied and evaluated with 5-fold cross-validation and also tested on the unseen data records of a collected dataset for proper evaluation and analysis. The proposed approaches were verified after analysing various performance metrics. The logistic regression technique achieved the highest average accuracy of 82.25% and the highest average F1-score of 82.58% among all the methods. Ridge classifiers and the Gaussian Naïve Bayes classifier achieved the highest sensitivity-85%. The ridge classifier surpasses most of the machine learning classifiers with 84.78% accuracy and 97.83% sensitivity. The risk factors analysed in this study can be taken as biomarkers in developing a cervical cancer diagnosis system. The outcomes demonstrate that the machine learning assisted analysis of cytokine gene variants and socio-demographic characteristics can be utilised effectively for predicting the risk of developing cervical cancer.

Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion.

This paper describes a rare case in which the oral administration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-aminosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, diarrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the importance of ruling out mesalamine as the causative agent in cases of UC exacerbations.