Evaluation of 17 genetic variants in association with leukemia in the north Indian population using MassARRAY Sequenom.

Leukemia is a heterogeneous disorder, characterized by elevated proliferation of white blood cells. In this study, we explored the association of 17 genetic variants with leukemia patients in the Jammu and Kashmir region of north India. The variants were genotyped by using a high-throughput Agena MassARRAY platform in 758 individuals (166 cases and 592 controls). Of the 17 single-nucleotide polymorphisms (SNPs) studied, five SNPs were showing significant association with the high risk of leukemia in the north Indian population, which includes rs10069690 of telomere reverse transcriptase (TERT) with OR = 0.34 (95% CI, 0.20-0.58; p = .0008), rs2972392 (​​​PSCA) with OR 1.86 (95% CI, 1.04-3.81; p = .035), rs4986764 (BRIP1) with OR 1.34 (95% CI, 1.00-1.80; p = .04), rs6990097 (TNKS) with OR 1.81 (95% CI, 1.2-2.6; p = .001) and rs12190287 (TCF21) with OR 2.87 (95% CI, 1.72-4.7; p = .0001) by allelic association using Plink and analyzed by SPSS. This is the first study to explore these variants with leukemia in the studied population.

MassARRAY-based single nucleotide polymorphism analysis in breast cancer of north Indian population.

BACKGROUND: Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. METHODS: SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. RESULTS: The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08-2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136-5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123-0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46-0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. CONCLUSION: It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Association of newly identified genetic variant rs2853677 of TERT with non-small cell lung cancer and leukemia in population of Jammu and Kashmir, India.

BACKGROUND: Telomere genetics has recently been emerged as an important field in molecular oncology. Various genome-wide association studies in different population groups have revealed that polymorphisms in Telomere maintenance gene (TERT) gene located on 5p15.33 is associated with susceptibility to leukemia and lung cancer risk. However, association of TERT with leukemia and lung cancer risk in north Indian population groups is still unknown. This study observed the association between genetic variant rs2853677 of TERT and leukemia and lung cancer in the state of Jammu and Kashmir, India. METHODS: A total of 781 subjects, out of which 381 cases (203 leukemic patients and 178 non-small cell lung cancer patients NSCLC) and 400 healthy controls were recruited for the study. Genetic variant rs2853677of TERT was detected using the real-time and Taqman Chemistry. Hardy-Weinberg Equilibrium was assessed using the chi square test. The allele and genotype- specific risks were estimated as odds ratio with 95% confidence interval. RESULTS: We observed that variant rs2853677 was strongly associated with lung cancer and leukemia risk with an odds ratio (OR) =1.8 (1.03-3.2 at 95% CI); p value (adjusted) = 0.03; odds ratio (OR) =2.9 (1.4-5.5.at 95% CI); p value (adjusted) = 0.002, respectively. CONCLUSION: The results of this study suggested that rs2853677 of TERT signifies association in multiple cancers and suggests that it can become potential marker for diagnosis of non-small cell lung cancer and leukemia. The study will provide an insight in understanding the genetic etiology and highlights the role of telomere-associated pathways in non-small cell lung cancer and leukemia. However, it would be quite interesting to explore the contribution of this variant in other cancers as well.

Psychological impact of COVID-19 pandemic on cancer patients: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) has globally impacted not only physical wellbeing but also the mental aspects in a far more extensive manner. The prevalence of psychological issues in cancer patients is much higher than in the general population, and the same has been impacted more during the COVID-19 pandemic. The purpose of this study was to estimate the psychological impact of COVID-19 on the mental health of cancer patients with no prior history of any form of mental disease. Methodology: A cross-sectional study of both inpatients and outpatients undergoing treatment and follow-up for different forms of cancer was conducted, and patients were assessed for perceived risk, anxiety, and depression. Results: Among the total of 150 participants, 31.8% of patients reported fear and concern. The major concern was regarding fear of treatment delay and fear of getting lonely. Over the prevalence of anxiety disorder with a cut-off score of ≥10 based on Generalized Anxiety Disorder-7 and Patient Depression Health Questionnaire-9 were 34% and 24%, respectively. Patient with female gender, married, being treated for ovarian cancer and who does not have metastatic changes were more anxious. Depressive symptoms were more in female patients, those who are married, and in the group with treatment delay due to COVID-19. Conclusion: There is urgent need for psychological intervention among cancer patients as there is an increase in mental health problems in this special group due to COVID-19 pandemic.

Sexual function status after adjuvant radiation including vaginal cuff brachytherapy in survivors of cancer cervix.

CONTEXT: Adjuvant radiation therapy plays an important role in the management of high-risk cervical cancer after radical hysterectomy or inadvertent hysterectomy. The prime concern with the use of dual modality is steep decline in sexual well-being in cervical cancer survivors. Intravaginal brachytherapy (IVBT) delivered by vaginal cylinder or ovoids is essential for local control but at the cost of impairment of sexual function. AIM: The purpose of this study was to assess the sexual well-being of cervical cancer survivors, who underwent surgery followed by adjuvant radiation and compare the subgroups of ovoids with sorbo brachytherapy. SETTINGS AND DESIGN: This was an observational, cross-sectional, and analytical study, whereby we evaluated sexual function of cervical cancer survivors by the Female Sexual Function Index (FSFI) instrument. SUBJECTS AND METHODS: Seventy-five women, identified as cervical cancer survivors who had received adjuvant radiation and IVBT, were administered FSFI questionnaire in face-to-face interviews. RESULTS: The mean age of 75 interviewed women was 48.64 years. Fifty survivors had received IVBT with a sorbo applicator and twenty-five with ovoids. FSFI full score ranged from 4.4 to 32.40. The mean full score for the whole group was 11.3. The mean FSFI full score was 24.91 (± standard deviation [SD] 5.71) in the ovoid group versus 4.49 (± SD 0.35) in the sorbo group. On Pearson's correlation analysis, age and type of brachytherapy were significantly correlated with FSFI full score (P = 0.006) with correlation coefficient of - 0.312 and - 0.948, respectively. CONCLUSIONS: Sexual dysfunction was found prevalent in 83% of cervical cancer survivors. The patients treated with IVBT with sorbo had worse sexual functioning than those treated with ovoids.

Evaluation of clinically significant prostate cancer using biparametric magnetic resonance imaging: An evolving concept.

Background: Multiparametric magnetic resonance imaging (mp-MRI) of prostate involves a combination of T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced (DCE) scans. However, controversy exists in the literature regarding the true value of DCE in the detection of clinically significant (CS) prostate cancer (PCa). Aim: The aim of this study is to compare the role of biparametric MRI (bp-MRI) and mp-MRI in the detection of CS PCa. Materials and Methods: Thirty-six patients with raised serum prostate-specific antigen levels were included. Bp-MRI was performed in all patients, whereas mp-MRI was performed in 30 cases only. The findings were characterized on the basis of prostate imaging reporting and data system (PI-RADS) v2 grading. PI-RADS v2 score of 3 or more was considered CS PCa. All patients underwent transrectal ultrasound-guided biopsy. Gleason score >6 was considered CS. Statistical analysis was done using the SPSS software and results interpreted. Results: CS PCa was observed in 31 cases on histopathology. On bp-MRI, CS PCa was seen in 31 patients. Five cases of PI-RADS v2 score 3 were seen on bp-MRI and 3 of them were upgraded to PI-RADS 4 on DCE images. One case of PI-RADS 3 had low Gleason score on biopsy, whereas 1 case of PI-RADS 2 had CS PCa on biopsy. No significant difference was observed between bp-MRI and mp-MRI in the detection of CS PCa. Conclusions: Both bp-MRI and mp-MRI have high sensitivity, specificity, and diagnostic accuracy and were nearly identical in the detection of CS PCa with no significant advantage of DCE images.

Incidence of xerostomia in locally advanced head-and-neck cancers in elderly patients treated with intensity-modulated radiotherapy.

Introduction: Dysphagia and xerostomia are the main sequelae of radiotherapy for head and neck cancer (HNC) and the main factors in reducing the longterm patient quality of life. Intensitymodulated radiotherapy (IMRT) uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of noninvolved tissues. Material and Methods: During 2016-2017, 44 patients of locally advanced HNCs were treated with a curative intent with IMRT. They were in the age range of 65-75 years. The median age was 69 years. Thirtyfive patients were male and nine patients were female. Histopathologically, all had squamous cell carcinoma. Stage wise all were T3N2 or more. No concurrent chemotherapy was given. The Eastern Clinical Oncology Group criteria were used for grading the toxicities. Patients were assessed after 4 weeks of completion of treatment. Results and Conclusion: The incidence of mucositis was of Grade 1-2 in 37 patients. Moreover, patients experienced severe mucositis. Six patients had treatment interruptions due to mucositis. Xerostomia was Grade 1-2 in 42 patients and Grade 3 in 2 patients. Dysphagia was Grade 1-2 only. No hematological toxicity was seen. Patients having dysphagia during the treatment were given nasogastric feed. Response wise 14 patients achieved complete response, 28 patients had partial response, and 2 had stable disease. There was no treatmentrelated mortality.

Intensity-modulated radiotherapy in locally advanced head-and-neck cancers in elderly patients.

Introduction: Head and neck cancer is one of the most common malignancies in Indian males. Due to poor socioeconomic status, presentation is usually in advanced stage. Treatment option is limited to radiotherapy with or without chemotherapy. Intensity-modulated radiotherapy (IMRT) provides highly conformal dose distributions creating nonuniform spatial intensity using different segments in the beam. Concomitant chemoradiation is highly toxic in this age group. Material and Methods: During 2016-2017, 44 patients with locally advanced head-and-neck cancers were treated with a curative intent with IMRT. They were in the age range of 65-75. The median age was 69 years. Thirty five were male and nine were female. Histopathologically, all had squamous cell carcinoma. Stage wise, all were T3N2 or more. The standard technique of IMRT was used with sparing of organs at risk and defining treatment volumes: gross, clinical, and planning. Patients were assessed after 4 weeks of completion of treatment for response and toxicities. Results: Response vise, 14 patients achieved complete response, 28 patients had partial response, and 2 had stable disease. There was no treatment-related mortality. Six patients had treatment interruptions due to toxicity. Incidence of mucositis was of Grade 1-2 in all patients. No hematological toxicity was seen. Patients having dysphagia during treatment were given nasogastric feed.

Gastric cancer in Jammu and Kashmir, India: A review of genetic perspectives.

Gastric Carcinoma (GC) is one of the most common malignancies, which accounts for 6.8% of total cancer population worldwide. In India, the northeastern region has the highest gastric cancer incidence, and the Kashmir Valley has a very high incidence of gastric cancer as compared to other parts of Northern India. It exceeds 40% of total cancers with an incidence rate of 3-6-fold higher than other metro cities of India. Gastric cancer is a heterogeneous disease where most of the cases are sporadic, and <15% are due to obvious familial clustering. The heterogeneous nature of the disease can be associated with differences in genetic makeup of an individual. A better understanding of genetic predisposition toward GC will be helpful in promoting personalized medicine. The aim of this review is to analyze the development and progression of GC and to explore the genetic perspectives of the disease with special emphasis on Jammu and Kashmir, India.

Genetic evaluation of the variants using MassARRAY in non-small cell lung cancer among North Indians.

Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). The present case-control association study focused on the cost effective high throughput genotyping using Agena MassARRAY matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) platform to analyze the genetic association of candidate genetic variants. We performed multiplex PCR and genotyped twelve single nucleotide polymorphisms (SNPs) in 723 samples (162 NSCLC cases and 592 healthy controls). These genetic variants were selected from literature for their association with various cancers worldwide and this is the first study from the region to examine these critically important genetic variants. With prospective case-control association study design, twelve variants from ten genes were evaluated. Amongst these six variants, TCF21 (rs12190287), ERCC1 (rs2298881, 11615), ERCC5 (rs751402), ARNTL (rs4757151), BRIP1 (rs4986764) showed significant association with NSCLC risk (p ≤ 0.003) in Jammu and Kashmir population. In-silico findings of these genetic variants showed remarkable functional roles that needs in-vitro validations. It is further anticipated that such case control studies will help us in understanding the missing heritability of non-small cell lung cancer.

Genetic variant rs2494938 of LRFN2 gene is associated with non-small cell lung cancer risk in North-Indian population.

Various Genome-wide association studies (GWAS) have reported the association of variant rs2494938 with lung cancer. However, genetic association of LRFN2 genetic variation with non-small cell lung cancer (NSCLC) in North Indian population remained unexplored. We conducted a case-control association study using TaqMan-based chemistry in which a total of 619 individuals, 189 NSCLC cases and 430 controls, were genotyped to explore the association of rs2494938 genetic variant of the LRFN2 gene with NSCLC patients from North India. The allele 'G' (risk allele) of the genetic variant rs2494938 was significantly associated with the NSCLC [OR = 1.51 (1.18-1.93 at 95% CI); p value = 0.0009]. Genetic association was also explored by applying different genetic models (Dominant, Additive). These results suggest that rs2494938 polymorphism of the LRFN2 gene is a risk factor in the North Indian populations to develop NSCLC. The LD (Linkage Disequilibrium) plot demonstrates the variant and its LD SNPs (r 2 > 0.8) and the variant has direct regulatory effect, which could affect the overall physiology of the gene. These findings could be used as diagnostic and prognostic markers in clinical studies of lung cancer patients in North Indian population groups. The present study also provides an important evidence on the genetic etiology of NSCLC in North Indian populations and further expounds GWAS findings on the role of LRFN2 in lung cancer risk. This study provides the holistic view about the non-small cell lung cancer in Jammu and Kashmir, North Indian population and it can be a hallmark of cancer if verified on a very large sample size (cohort).

Sexual Dysfunction in Carcinoma Cervix: Assessment in Post Treated Cases by LENTSOMA Scale.

Treatment for cervical cancer consists of hysterectomy, radiotherapy, chemotherapy and targeted therapy in different combination based on stage at presentation. However, late consequences of such radical treatments are known but not many Indian studies have reported it. Quality of life and impact on sexual health has become an important issue in view of long survival of cervical cancer patients. LENTSOMA scale is one such scale validated for scoring radiotherapy related morbidity. However, there is need for a comprehensive scale covering all aspects of physical and psychological disruptions to provide complete recovery and rehabilitation. The study was prospective and patients who were treated for cervical cancer on follow up were included in this study. A total of 85 patients, who were treated with surgery, radiotherapy, chemotherapy alone or in combination, comprising of stage I to stage IV disease, participated in this study. Findings of this study showed that pain during intercourse and altered sexual life were reported by 32.9% and 25.9% patients respectively whereas 24.7% found it problematic and in 22.3% patients, alteration in interest in sex were reported. Vaginal stenosis was seen in 75.29% of patients after treatment with decreased frequency of intercourse after treatment was seen in 16.4 % of patients. Combination of surgery and radiotherapy in cervical cancer patients caused more sexual dysfunction and dissatisfaction, especially in lower age group. Treatment morbidity in term of sexual function was more with advanced stage disease and with the patients on longer follow up. Sexual function is an important aspect of quality of life but there is no single self-report measure in routine clinical follow up use which is brief, easy to complete and incorporates all (physical, psychological, emotional) aspects of sexual health for people affected by cancer.
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Genetic variants of DNAH11 and LRFN2 genes and their association with ovarian and breast cancer.

OBJECTIVE: To investigate the association of newly identified genetic variants G>A (rs2285947) of the DNAH11 gene and G>A (rs2494938) of the LRFN2 gene with ovarian and breast cancers in women belonging to Jammu and Kashmir state, where the prevalence of ovarian and breast cancers is remarkably high in the population. METHODS: A candidate gene prospective case-control association study design was adopted, in which 354 cases (219 cases of ovarian cancer and 135 cases of breast cancer) were histopathologically confirmed and 330 healthy controls matched for age and ethnicity were recruited. The details of cases and controls were also recorded in a predesigned pro forma after their written informed consent. Both variants were genotyped by TaqMan allele discrimination assay using real-time polymerase chain reaction. Logistic regression analysis was performed to estimate the corrected odds ratio (OR), confidence interval (CI), and level of significance (P value) for potential confounding factors. RESULTS: The rs2285947 variant of DNAH11 was found to be significantly associated with both ovarian and breast cancers with adjusted ORs of 1.7 (95% CI 1.2-2.4; P=0.004) and 1.70 (95% CI 1.13-2.54; P=0.0009), respectively. However, no significant association of variant rs2494938 of LRFN2 was observed with ovarian cancer (estimated OR 0.9, 95% CI 0.6-1.4; P=0.919) or breast cancer (estimated OR 1.27, 95% CI 0.8-1.9; P=0.216). CONCLUSIONS: The collected data proposed that the variant rs2285947 of DNAH11 gene is a potential risk factor for ovarian and breast cancers in the studied population.

DNA base excision repair genes variants rs25487 (X-ray repair cross-complementing 1) and rs1052133 (human 8-oxoguanine glycosylase 1) with susceptibility to ovarian cancer in the population of the Jammu region, India.

BACKGROUND: Ovarian cancer is highly prevalent in the population of Jammu, in India; the ovarian cancer ranks third among other types of cancer prevalent in females. However, association studies on ovarian cancer are lacking in this region. We aimed to investigate the disease susceptible variants rs1052133 (human 8-oxoguanine glycosylase 1 [hOGG1]) and rs25487 (X-ray repair cross-complementing 1 [XRCC1]) with ovarian cancer in population of Jammu, India. MATERIALS AND METHODS: The study conducted in the Shri Mata Vaishno Devi University is a 3-year study which included a total of 280 well-characterized samples (130 ovarian cancer cases and 150 healthy controls). hOGG1 and XRCC1 polymorphisms were determined by polymerase chain reaction-based restriction fragment length polymorphism, and these genotyping results were confirmed by Sanger sequencing. Hardy-Weinberg equilibrium for both single-nucleotide polymorphisms (SNPs) was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios with 95% confidence intervals. RESULTS: In this preliminary study, SNP rs1052133 showed protection with ovarian cancer (P = 0.042). The SNP rs25487 was not found associated with ovarian cancer (P = 0.271). CONCLUSION: Our results indicate that the G allele of rs1052133 imparts protection to the population whereas variant rs25487 was not associated with ovarian cancer in population from the Jammu region, indicating that larger sample size is needed for further statistical validation. Further, association of other SNPs in these genes should also be carried out as their role cannot be ruled out.

Genetic variant rs10937405 of TP63 and susceptibility to lung cancer risk in north Indian population.

Several studies including genomewide association studies (GWASs) in diverse ethnic populations have reported a significant association of genetic variant rs10937405 of TP63 with nonsmall cell lung cancer (NSCLC). However, no data are available from any Indian population on the association of this variant with NSCLC. Using TaqMan genotyping chemistry, we conducted a case-control study involving 190 NSCLC cases and 400 ethnic, age-matched controls to explore the association of rs10937405 genetic variant with NSCLC in patients from north India. Our data support that the rs10937405 variant is also significantly associated with the NSCLC and is a risk factor in the north Indian populations to develop NSCLC. However, unlike most other studies, the wild-type allele T appears to be the risk allele, as its frequency was significantly higher in the cases than controls (0.439 in cases versus 0.383 in controls. OR=1.95 (1.23-3.09 at 95% CI); P value (adjusted)= 0.004). Genetic association was also observed by applying different genetic models. The present study provides important information of the genetic aetiology of NSCLC and strengthens GWAS findings, highlighting the role of TP63 in lung cancer risk.