Exome sequencing identifies ADGRG4 G-protein-coupled receptors gene as a novel cancer biomarker in ovarian cancer patients from North India.

Adhesion G protein-coupled receptor G4 (ADGRG4) is a G protein-coupled receptor (GPCR) that belongs to the adhesion family. Participation of ADGRG4 in cell adhesion and migration, signaling pathway activation, influence on angiogenesis, and modulation of immune responses are some of the possible ways through which it may contribute to oncogenesis. Conducting extensive omics studies poses budgetary challenges to small labs in peripheral areas, primarily due to restricted research funding and resource limitations. Here we propose a low-budget model for biomarker screening. A total of 11 ovarian cancer samples were sent for exome sequencing. Among various genes, ADGRG4 variants were present in all 11 samples and thus were chosen as a potential biomarker in the present population. However, the precise role of ADGRG4 in cancer is not fully understood. The present study aims to look at the association between the ADGRG4 gene variants and their risk of ovarian cancer in the North Indian region of Jammu and Kashmir, India. Overall, 235 individuals (115 cases and 120 healthy controls) were genotyped for the selected biomarker using Sanger sequencing. Logistic regression was used to assess the relationship between the variant and ovarian cancer. A statistically significant association was identified between the ADGRG4 variant rs5930932 polymorphism and the incidence of ovarian cancer among the study population. When corrected for age and BMI, the dominating OR of variant rs5930932 was 1.035 (1.003-1.069) under HWE patients (0.95) and controls (0.18), with a p-value of (0.03). According to the findings of the current investigation, the ADGRG4 gene variant rs5930932 increases the chance of developing ovarian cancer in the studied population.

Genetic analysis of colorectal carcinoma using high throughput single nucleotide polymorphism genotyping technique within the population of Jammu and Kashmir.

BACKGROUND: SNP genotyping has become increasingly more common place to understand the genetic basis of complex diseases like cancer. SNP-genotyping through MassARRAY™ is a cost-effective method to quantitatively analyse the variation of gene expression in multiple samples, making it a potential tool to identify the underlying causes of colorectal carcinogenesis. METHODS: In the present study, SNP genotyping was carried out using Agena MassARRAY™, which is a cost-effective, robust, and sensitive method to analyse multiple SNPs simultaneously. We analysed 7 genes in 492 samples (100 cases and 392 controls) associated with CRC within the population of Jammu and Kashmir. These SNPs were selected based on their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with colorectal cancer within the J&K population.7 SNPs with a call rate of 90% were selected for the study. Out of these, five SNPs rs2234593, rs1799966, rs2229080, rs8034191, rs1042522 were found to be significantly associated with the current study under the allelic model with an Odds Ratio OR = 2.981(1.731-5.136 at 95% CI); p value = 4.81E-05 for rs2234593,OR = 1.685(1.073-2.647 at 95% CI);; p value = 0.02292 for rs1799966, OR = 1.5 (1.1-2.3 at 95% CI), p value = 0.02 for rs2229080, OR = 1.699(1.035-2.791 at 95% CI); p value = 0.03521 for rs8034191, OR = 20.07 (11.26-35.75); p value = 1.84E-34 for rs1042522 respectively. CONCLUSION: This is the first study to find the relation of Genetic variants with the colorectal cancer within the studied population using high throughput MassARRAY™ technology. 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.

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.

Pre and post treatment quality of life among patients of hepatobiliary and pancreatic cancers in North India: A prospective study.

Context: Studies reporting quality of life (QOL) measures alongside conventional measures of effectiveness of interventions and outcome are essential. Aims: We aimed to compare QOL and mental well-being in hepatobiliary and pancreatic cancer patients before and after receiving treatment. Settings and Design: This was a hospital-based prospective study. Methods and Materials: The study was conducted in North India for a period of 1 year. QOL was assessed in 118 patients using the Functional Assessment of Cancer Therapy-Hepatobiliary Scale and Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Level 1 Cross-Cutting Symptom Measure-Adult was used to assess the psychiatric domains of subjects. Statistical Analysis Used: The data were analyzed using MS Excel and SPSS version 23. Statistical significance between QOL scores at baseline and 12 weeks was evaluated by Student's t-test. Pre- and post-Cronbach's alpha reliability coefficient was also calculated. Results: 59.4% of subjects were females and 40.6% were males. Carcinoma gallbladder was the predominant cancer (2/3rd) followed by carcinoma pancreas (1/3rd). Both pre- and posttreatment reliability coefficients showed values ≥ 0.75, indicating that the questionnaire reliably measured different domains of health-related QOL, both on generic and disease-specific scales. Using paired t-test, a significant difference was observed only in the physical (P = 0.001) and functional (P = 0.0002) domains. There was a slight increase in proportion of patients demonstrating improvement in severity of depression and anxiety at 6-12 weeks and the number of patients experiencing moderate symptoms of sleep disorders and somatic disorders. The number of patients experiencing severe symptoms of anger decreased posttreatment. Conclusions: QOL is amenable to improvement with timely interventions including counseling.

Solitary plasmacytoma of the proximal tibia in an adolescent.

This is the case report of a 14-year young female who was diagnosed with solitary bone plasmacytoma (SBP) of proximal tibia and was treated by local involved field radiotherapy. We present the clinical, radiological and pathological findings of the case and review of the available treatment options and prognosis of this rare site presentation of plasmacytoma in an adolescent female.

Genetic association of ARID5B with the risk of colorectal cancer within Jammu and Kashmir, India.

Colorectal cancer (CRC), which includes the development of cancer from the colon or rectum, is one of the highly prevalent cancers in the populations of Jammu and Kashmir (J&K) in India. However, case-control genetic association studies on CRC are lacking in this population. Various genome-wide association studies have previously shown that single-nucleotide polymorphisms (SNPs) of the AT-rich interaction domain 5B (ARID5B) gene located on chromosome 10q21.2 contribute substantially to the development of colorectal cancer. The association between ARID5B and CRC risk in north Indian population groups is still unknown. To understand the role of ARID5B SNPs in CRC in the population of J&K, we designed a case-control study to investigate the association of the cancer susceptibility variant rs10740055 of ARID5B with CRC in the population of J&K. The study included 180 cases and 390 healthy controls. Genotyping of the rs10740055 variant was performed by RT-PCR using the TaqMan assay technique. Hardy-Weinberg equilibrium of the variant was assessed using the chi-squared test. The allele- and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). The rs10740055 variant showed a higher risk for colorectal cancer with an OR of 3.35 (1.99-5.65 at 95% CI) and P = 0.000005 corrected for age, gender, ethnicity, BMI, alcohol intake and smoking. Our results indicate that the A allele of rs10740055 imparts risk to the population and also that a larger sample size is needed for further statistical validation. The association of other variants in other ARID family genes should also be tested as their role cannot be ruled out.

Evaluation of newly identified Ikaros family zinc finger 1 loci in colorectal cancer.

AIM: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). MATERIALS AND METHODS: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. RESULTS: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34-2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011-4.76) at 95% CI, P > 0.05. CONCLUSIONS: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.

Evaluation of outcome and prognostic factors in patients of glioblastoma multiforme: A single institution experience.

AIMS: We present retrospective analysis of patients of glioblastoma multiforme (GBM) and discuss clinical characteristics, various treatment protocols, survival outcomes, and prognostic factors influencing survival. MATERIALS AND METHODS: From January 2002 to June 2009, 439 patients of GBM were registered in our department. The median age of patients was 50 years, 66.1% were males, and 75% underwent complete or near-total excision. We evaluated those 360 patients who received radiotherapy (RT). Radiotherapy schedule was selected depending upon pre-RT Karnofsky Performance Status (KPS). Patients with KPS < 70 (Group I, n = 48) were planned for RT dose of 30-35 Gy in 10-15 fractions, and patients with KPS ≥ 70 (Group II, n = 312) were planned for 60 Gy in 30 fractions. In group I, six patients and in group II, 89 patients received some form of chemotherapy (lomustine or temozolomide). STATISTICAL ANALYSIS USED: Statistical analysis was done using Statistical Package for Social Sciences, version 12.0. Overall survival (OS) was calculated using Kaplan-Meier method, and prognostic factors were determined by log rank test. The Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up was 7.53 months. The median and 2-year survival rates were 6.33 months and 2.24% for group I and 7.97 months and 8.21% for group II patients, respectively (P = 0.001). In multivariate analysis, site of tumor (central vs. others; P = 0.006), location of tumor (parietal lobe vs. others; P = 0.003), RT dose (<60 Gy vs. 60 Gy; P = 0.0001), and use of some form of chemotherapy (P = 0.0001) were independent prognostic factors for survival. CONCLUSIONS: In patients with GBM, OS and prognosis remains dismal. Whenever possible, we should use concurrent and/or adjuvant chemotherapy to maximize the benefits of post-operative radiotherapy. Patients with poor performance status may be considered for hypofractionated RT schedules, which have similar median survival rates as conventional RT.

Squamous cell carcinoma of supraglottic larynx with metastasis to all five distal phalanges of left hand.

Subcutaneous metastasis from carcinoma larynx is a rare presentation and to the phalynx is the rarest. We herein describe a case report of carcinoma supraglottic larynx, which is involving all five distal phalanges of left hand with simultaneous metastases to lung and liver. Acrometastasis is an unusual presentation, which might mimic an infectious or inflammatory pathology. The brief report highlights the importance of clinical awareness of metastatic dissemination to unusual sites in the face of increasing cancer survivorship.

Palliative and supportive care in acrometastasis to the hand: case series.

Acrometastasis to the hand is an unusual presentation which might mimic an infectious, inflammatory, or a metabolic pathology. We herein describe a case series of three patients of acrometastasis to the hand. We encountered three cases of acrometastasis to the hand attending the departmental clinics from 2007 to 2010. The median age at presentation was noted to be 55 years. All were males. The primaries included squamous cell carcinoma of the skin, larynx, and esophagus. In two patients, acrometastasis was detected at presentation and in one it was detected 2 years postcompletion of radical therapy. Two patients were offered palliative radiation to acrometastasis, and best supportive care was given to one. Palliation achieved after radiation was noted to be modest to good. The brief report highlights the importance of the clinical awareness of metastatic dissemination to unusual sites in the face of increasing cancer survivorship. Acrometastasis portends a poor prognosis with limited survival, and optimal integration of the best supportive care is mandatory. A short course of hypofractionated palliative radiation therapy results in modest to good palliation.

Quadruple malignancy in a single patient: a case report and comprehensive review of literature.

The occurrence of multiple primary malignant neoplasias (MPMN) is a rare but increasingly frequently reported event. Many theories have been proposed to explain MPMNs, but none have been proven. The key risk factors appear to be smoking and family history. While numerous studies have been published on the development of second malignancies following a first primary, the literature contains only few case reports and reviews of patients with three or more malignancies. We report a case of a young female who, over a period of 30 years, developed four different malignancies and was treated radically on each occasion.