Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study.

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post-treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan-Meier analyses were performed. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35-80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was 0-1 in 28 patients and 2-3 in 12 patients. The best clinical response rate post-oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow-up was 6.4 months (4.5-9.2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade-I/II mucositis. Grade-III/IV mucositis were observed in 9 (22.5%) patients. Thirty-seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well-tolerated regime with good symptomatic control and low-moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade-III/IV thrombocytopenia.

Converting primary forests to cultivated lands: Long-term effects on the vertical distribution of soil carbon and biological activity in the foothills of Eastern Himalaya.

The conversion of primary forests to cultivation brings a significant change in soil carbon (C) forms. In the foothills of the Eastern Himalayan Region of India (Manipur), such conversions are prevalent. However, little is known about the response of C forms, particularly in deep soil, to land use conversion in the region. We evaluated changes in soil C forms (total organic, inorganic, and pools) and microbiological properties (up to 1.0 m depth) mediated by C when the 45-year-old forest had been cultivated for 18-25 years. The cultivated land uses were tree-based agroforestry (LAF: legumes, NAF: non-legumes), horticultural fruits (WHF: woody, NHF: non-wood, mainly vegetables), and paddy agriculture system (AUS: upland, ALS: lowlands). Forest conversion significantly (p < 0.05) decreased the total carbon (TC) in the surface soil (0.0-0.15 m) from 4.88 % to 3.04-3.93 % in the tree-based land uses (LAF, NAF, and WHF). TC further declined to 2.05-2.81 % under seasonal crops (NHF, AUS, and ALS). Seasonal crop cultivation also caused a higher decline in microbial biomass carbon, soil enzymes, and carbon pools (active and passive) than the tree-based land use with the soil depth. The vertical distribution of C in the soil profile was inconsistent: organic C (including C pools) decreased, while inorganic C increased. The profile TC stock to a depth of 1.0 m in the forest was 358.8 Mg ha-1, of which 81 % were organic C, and 19 % were inorganic C. In comparison with forest soil, total soil C stocks (organic and inorganic) decreased more (-44.1 to -55.1 %) in seasonal crops than in tree-based (-15.4 to -36.3 %) land uses. The degradation index (DI) also confirmed that seasonal crop cultivation caused a larger decline in surface soil quality (DI: -423 % to -623 %) than tree-based land use (DI: -243 % to -317 %). The topsoil (up to 0.45 m) of seasonal crops was more degraded than that of the subsoil (>0.45 m-1.0 m). Forests converted to seasonal cultivation (upland rice and vegetables) caused higher degradation of soil C forms and overall soil health in the Himalayan foothills of northeastern India. We suggest the promotion of Agroforestry based on legumes (Parkia spp.) and woody fruits (mango/citrus/guava) in the uplands to minimize soil C degradation while ensuring nutritional security in the hill agro-ecosystems of the Indian Himalayas.

Using PET for therapy monitoring in oncological clinical trials: challenges ahead.

Molecular imaging with PET has emerged as a powerful imaging tool in the clinical care of oncological patients. Assessing therapy response is a prime application of PET and so the integration of PET into multicentre trials can offer valuable scientific insights and shape future clinical practice. However, there are a number of logistic and methodological challenges that have to be dealt with. These range from availability and regulatory compliance of the PET radiopharmaceutical to availability of scan time for research purposes. Standardization of imaging and reconstruction protocols, quality control, image processing and analysis are of paramount importance. Strategies for harmonization of the final image and the quantification result are available and can be implemented within the scope of multicentre accreditation programmes. Data analysis can be performed either locally or by centralized review. Response assessment can be done visually or using more quantitative approaches, depending on the research question. Large-scale real-time centralized review can be achieved using web-based solutions. Specific challenges for the future are inclusion of PET/MRI scanners in multicentre trials and the incorporation of radiomic analyses. Inclusion of PET in multicentre trials is a necessity to guarantee the further development of PET for routine clinical care and may yield very valuable scientific insights.

Hippocampal Neurometabolite Changes in Hypothyroidism: An In Vivo (1) H Magnetic Resonance Spectroscopy Study Before and After Thyroxine Treatment.

The hippocampus is a thyroid hormone receptor-rich region of the brain. A change in thyroid hormone levels may be responsible for an alteration in hippocampal-associated function, such as learning, memory and attention. Neuroimaging studies have shown functional and structural changes in the hippocampus as a result of hypothyroidism. However, the underlying process responsible for this dysfunction remains unclear. Therefore, the present study aimed to investigate the metabolic changes in the brain of adult hypothyroid patients during pre- and post-thyroxine treatment using in vivo proton magnetic resonance spectroscopy ((1) H MRS). (1) H MRS was performed in both healthy control subjects (n = 15) and hypothyroid patients (n = 15) (before and after thyroxine treatment). The relative ratios of the neurometabolites were calculated using the linear combination model (LCModel). Our results revealed a significant decrease of glutamate (Glu) (P = 0.045) and myo-inositol (mI) (P = 0.002) levels in the hippocampus of hypothyroid patients compared to controls. No significant changes in metabolite ratios were observed in the hypothyroid patients after thyroxine treatment. The findings of the present study reveal decreased Glu/tCr and mI/tCr ratios in the hippocampus of hypothyroid patients and these metabolite alterations persisted even after the patients became clinically euthyroid subsequent to thyroxine treatment.

Alterations of Functional Connectivity Among Resting-State Networks in Hypothyroidism.

Hypothyroidism affects brain functioning as suggested by various neuroimaging studies. The primary focus of the present study was to examine whether hypothyroidism would impact connectivity among resting-state networks (RSNs) using resting-state functional magnetic resonance imaging (rsfMRI). Twenty-two patients with hypothyroidism and 22 healthy controls were recruited and scanned using rsfMRI. The data were analysed using independent component analysis and a dual regression approach that was applied on five RSNs that were identified using fsl software (http://fsl.fmrib.ox.ac.uk). Hypothyroid patients showed significantly decreased functional connectivity in the regions of the right frontoparietal network (frontal pole), the medial visual network (lateral occipital gyrus, precuneus cortex and cuneus) and the motor network (precentral gyrus, postcentral gyrus, precuneus cortex, paracingulate gyrus, cingulate gyrus and supramarginal gyrus) compared to healthy controls. The reduced functional connectivity in the right frontoparietal network, the medial visual network and the motor network suggests neurocognitive alterations in hypothyroid patients in the corresponding functions. However, the study would be further continued to investigate the effects of thyroxine treatment and correlation with neurocognitive scores. The findings of the present study provide further interesting insights into our understanding of the action of thyroid hormone on the adult human brain.

A study of predictors for identification of risk of complications in patients with liver abscess.

BACKGROUND/AIMS: Liver abscess is a significant health problem in developing countries and the complications associated with it are frequently fatal. Hence identification of these complications and anticipating the same will lead to reduction in the mortality and morbidity rate. Such a work will facilitate in identifying patients with risk of complications and will allow for planning of an early intervention. The aim of this study was to identify the predictors of risk of complications in patients with liver abscess. MATERIALS AND METHODS: The data for this retrospective study was obtained from hospital records and included 100 patients diagnosed to have solitary or multiple liver abscess. Complications were defined and history, lab and radiological findings and course of treatment were observed and analyzed in correlation with occurrence of complications. A predictive scoring system was designed for 15 points by giving two points to the factors with 100% correlation and one point to other factors with strong correlation. The score was applied to a validation cohort of 114 different patients and results were noted. RESULTS: Out of the 100 cases studied 24 cases had complications of and the predictive factors included history of alcoholism (> 10 yrs), INR > 1.7 , TLC > 20000/cc and pleural effusion, while other factors had a varying degree of correlation with complication occurrence. It was observed that the new scoring system was successful in identifying patients at risk of developing complications with 100% sensitivity and 93.75% specificity. CONCLUSION: Management of liver abscess can be clearly defined by dividing patients into categories depending upon a new scoring system described in the study and intervention can be planned.

Diffusion tensor tractography in hypothyroidism and its correlation with memory function.

Diffusion tensor tractography (DTT) was performed to determine the microstructural changes in the white matter fibre tracts of hypothyroid patients compared to controls and to correlate these changes with memory dysfunction scores. DTT and Postgraduate Institute Memory Scale test were performed in eight hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was made between the patient group and controls. Pearson's correlation was performed between Memory Dysfunction score and DTI measures. Significant changes in DTI measures were observed in various white matter fibre tracts in hypothyroid patients compared to controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction score with FA was observed in the right and left inferior fronto-occipital fasciculus, whereas a positive correlation with MD was observed in the right anterior thalamic radiation among all white matter tracts. These findings suggest that microstructural changes in white matter fibres may contribute to the underlying dysfunction in memory in hypothyroid patients.

Voxel-based morphometric analysis in hypothyroidism using diffeomorphic anatomic registration via an exponentiated lie algebra algorithm approach.

The present study aimed to investigate whether brain morphological differences exist between adult hypothyroid subjects and age-matched controls using voxel-based morphometry (VBM) with diffeomorphic anatomic registration via an exponentiated lie algebra algorithm (DARTEL) approach. High-resolution structural magnetic resonance images were taken in ten healthy controls and ten hypothyroid subjects. The analysis was conducted using statistical parametric mapping. The VBM study revealed a reduction in grey matter volume in the left postcentral gyrus and cerebellum of hypothyroid subjects compared to controls. A significant reduction in white matter volume was also found in the cerebellum, right inferior and middle frontal gyrus, right precentral gyrus, right inferior occipital gyrus and right temporal gyrus of hypothyroid patients compared to healthy controls. Moreover, no meaningful cluster for greater grey or white matter volume was obtained in hypothyroid subjects compared to controls. Our study is the first VBM study of hypothyroidism in an adult population and suggests that, compared to controls, this disorder is associated with differences in brain morphology in areas corresponding to known functional deficits in attention, language, motor speed, visuospatial processing and memory in hypothyroidism.

Hydrocarbon phenotyping of algal species using pyrolysis-gas chromatography mass spectrometry.

BACKGROUND: Biofuels derived from algae biomass and algae lipids might reduce dependence on fossil fuels. Existing analytical techniques need to facilitate rapid characterization of algal species by phenotyping hydrocarbon-related constituents. RESULTS: In this study, we compared the hydrocarbon rich algae Botryococcus braunii against the photoautotrophic model algae Chlamydomonas reinhardtii using pyrolysis-gas chromatography quadrupole mass spectrometry (pyGC-MS). Sequences of up to 48 dried samples can be analyzed using pyGC-MS in an automated manner without any sample preparation. Chromatograms of 30-min run times are sufficient to profile pyrolysis products from C8 to C40 carbon chain length. The freely available software tools AMDIS and SpectConnect enables straightforward data processing. In Botryococcus samples, we identified fatty acids, vitamins, sterols and fatty acid esters and several long chain hydrocarbons. The algae species C. reinhardtii, B. braunii race A and B. braunii race B were readily discriminated using their hydrocarbon phenotypes. Substructure annotation and spectral clustering yielded network graphs of similar components for visual overviews of abundant and minor constituents. CONCLUSION: Pyrolysis-GC-MS facilitates large scale screening of hydrocarbon phenotypes for comparisons of strain differences in algae or impact of altered growth and nutrient conditions.

Lessons learned from independent central review.

Independent central review (ICR) is advocated by regulatory authorities as a means of independent verification of clinical trial end-points dependent on medical imaging, when the data from the trials may be submitted for licensing applications [Food and Drug Administration. United States food and drug administration guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. Rockville, MD: US Department of Health and Human Services; 2007; Committee for Medicinal Products for Human Use. European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) guideline on the evaluation of anticancer medicinal products in man. London, UK: European Medicines Agency; 2006; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 21-492 (oxaliplatin). Rockville, MD: US Department of Health and Human Services; 2002; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 21-923 (sorafenib tosylate). Rockville, MD: US Department of Health and Human Services; 2005; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 22-065 (ixabepilone). Rockville, MD: US Department of Health and Human Services; 2007; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 22-059 (lapatinib ditosylate). Rockville, MD: US Department of Health and Human Services; 2007; United States Food and Drug Administration Center for Biologics Evaluation and Research. Approval package for BLA numbers 97-0260 and BLA Number 97-0244 (rituximab). Rockville, MD: US Department of Health and Human Services; 1997; United States Food and Drug Administration. FDA clinical review of BLA 98-0369 (Herceptin((R)) trastuzumab (rhuMAb HER2)). FDA Center for Biologics Evaluation and Research; 1998; United States Food and Drug Administration. FDA Briefing Document Oncology Drugs Advisory Committee meeting NDA 21801 (satraplatin). Rockville, MD: US Department of Health and Human Services; 2007; Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. JCO 2007(November):5210-7]. In addition, clinical trial sponsors have used ICR in Phase I-II studies to assist in critical pathway decisions including in-licensing of compounds [Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. JCO 2007(November):5180-6; Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. JCO 2007(August):3407-14; Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. JCO 2007(June):2171-7; Ghassan KA, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. JCO 2006(September):4293-300; Boué F, Gabarre J, GaBarre J, et al. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. JCO 2006(September):4123-8; Chen HX, Mooney M, Boron M, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. JCO 2006(July):3354-60; Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. JCO 2006(June):2502-12; Jaffer AA, Lee FC, Singh DA, et al. Multicenter phase II trial of S-1 plus cisplatin in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma. JCO 2006(February):663-7; Bouché O, Raoul JL, Bonnetain F, et al. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Fédération Francophone de Cancérologie Digestive Group Study-FFCD 9803. JCO 2004(November):4319-28]. This article will focus on the definition and purpose of ICR and the issues and lessons learned in the ICR setting primarily in Phase II and III oncology studies. This will include a discussion on discordance between local and central interpretations, consequences of ICR, reader discordance during the ICR, operational considerations and the need for specific imaging requirements as part of the study protocol.

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

BACKGROUND: Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. FUTURE WORK: A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

Recommendations for the assessment of progression in randomised cancer treatment trials.

Progression-free survival (PFS) is an increasingly important end-point in cancer drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over-estimated (or under-estimated) and, consequently, bias may be introduced when comparing treatments. In addition, the assessment of progression is subject to measurement variability which may introduce error or bias. Ideally trials with PFS as the primary end-point should be randomised and, when feasible, double-blinded. All patients eligible for study should be evaluable for the primary end-point and thus, in general, have measurable disease at baseline. Appropriate definitions should be provided in the protocol and data collected on the case-report forms, if patients with only non-measurable disease are eligible and/or clinical, or symptomatic progression are to be considered progression events for analysis. Protocol defined assessments of disease burden should be obtained at intervals that are symmetrical between arms. Independent review of imaging may be of value in randomised phase II trials and phase III trials as an auditing tool to detect possible bias.

Validation of novel imaging methodologies for use as cancer clinical trial end-points.

The success or failure of a clinical trial, of any phase, depends critically on the choice of an appropriate primary end-point. In the setting of phases II and III cancer clinical trials, imaging end-points have historically, and continue presently to play a major role in determining therapeutic efficacy. The primary goal of this paper is to discuss the validation of imaging-based markers as end-points for phase II clinical trials of cancer therapy. Specifically, we outline the issues that must be considered, and the criteria that would need to be satisfied, for an imaging end-point to supplement or potentially replace RECIST- defined tumour status as a phase II clinical trial end-point. The key criteria proposed to judge the utility of a new end-point primarily relate to its ability to accurately and reproducibly predict the eventual phase III end-point for treatment effect, which is usually assessed by a difference between two arms on progression free or overall survival, both at the patient and more importantly at the trial level. As will be demonstrated, the level of evidence required to formally and fully validate a new imaging marker as an appropriate end-point for phase II trials is substantial. In many cases, this level of evidence will only become available by conducting a series of coordinated prospectively designed multicentre clinical trials culminating in a formal meta-analysis. We also include a discussion of situations where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate inevitable real-world feasibility constraints.

Evaluation of lymph nodes with RECIST 1.1.

Lymph nodes are common sites of metastatic disease in many solid tumours. Unlike most metastases, lymph nodes are normal anatomic structures and as such, normal lymph nodes will have a measurable size. Additionally, the imaging literature recommends that lymph nodes be measured in the short axis, since the short axis measurement is a more reproducible measurement and predictive of malignancy. Therefore, the RECIST committee recommends that lymph nodes be measured in their short axis and proposes measurement values and rules for categorising lymph nodes as normal or pathologic; either target or non-target lesions. Data for the RECIST warehouse are presented to demonstrate the potential change in response assessment following these rules. These standardised lymph node guidelines are designed to be easy to implement, focus target lesion measurements on lesions that are likely to be metastatic and prevent false progressions due to minimal change in size.

Cancer lung: An unusual presentation.

Phalanx bone metastasis as the initial manifestation of lung cancer is a rare presentation. A 70-year-old man presented with swelling and pain in his right ring finger. He had no other complaints or abnormal findings on clinical examination. A right hand radiograph showed an osteolytic lesion in the first phalanx of the ring finger. Fine needle aspiration cytology of the swelling suggested a metastatic adenocarcinoma. A skeletal survey, hematological, biochemical, and other radiological tests were found to be normal, except for an opacity seen in the right lung midzone. A bronchoscopic biopsy revealed adenocarcinoma of the lung.

Magnetic resonance spectroscopy as a diagnostic modality for carcinoma thyroid.

AIM: The aim of this study was to observe the findings of magnetic resonance spectroscopy of solitary thyroid nodules and its correlation with histopathology. MATERIALS AND METHODS: In this study, magnetic resonance spectroscopy was carried out on 26 patients having solitary thyroid nodules. Magnetic resonance spectroscopy (MRS) was performed on a 1.5T super conductive system with gradient strength of 33mTs. Fine needle aspiration cytology was done after MRS. All 26 patients underwent surgery either because of cytopathologically proven malignancy or because of cosmetic reasons. Findings of magnetic resonance spectroscopy were compared with histopathology of thyroid specimens. RESULTS AND CONCLUSION: It was seen that presence or absence of choline peak correlates very well with presence or absence of malignant foci with in the nodule (sensitivity=100%; specificity=88.88%). These results indicate that magnetic resonance spectroscopy may prove to be an useful diagnostic modality for carcinoma thyroid.

The uterine compression suture--a valuable approach to control major haemorrhage at lower segment caesarean section.

The aim of this article is to review the efficacy of a modified uterine compression suture in controlling major haemorrhage at lower segment caesarean section. This is a descriptive study of patients who had major obstetric haemorrhage where a compression suture was used to control bleeding at the two obstetrics unit in Cardiff between January 1998 and December 2003 (n = 11).

Genetic polymorphism of drug metabolizing enzymes (CYP2E1, GSTP1) and susceptibility to bladder cancer in North India.

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca-B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype prevalence and their associations between patient and the control group. We observed a non-significant association in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination with tobacco users were highly significant (OR=24.06; 95% CI: 4.80- 120.42; P =0.000) when compared to the controls. The results of our study demonstrated that the GSTP1 313 G/G polymorphism is a strong predisposing risk factor for bladder cancer in the North Indian population.