Identifying polymorphic cis-regulatory variants as risk markers for lung carcinogenesis and chemotherapy responses in tobacco smokers from eastern India.

Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case-control study with 3 promoter cis-eQTLs (p < 0.01) on 101 lung cancer patients and 401 healthy controls from eastern India with confirmed smoking history revealed an association of rs3764821 (ALDH3B1) (OR = 2.53, 95% CI = 1.57-4.07, p = 0.00014) and rs3748523 (RAD52) (OR = 1.69, 95% CI = 1.17-2.47, p = 0.006) with lung cancer risk. The effect of different chemotherapy regimens on the overall survival of lung cancer patients to the associated variants showed that the risk alleles of both variants significantly decreased (p < 0.05) patient survival.

No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population.

OBJECTIVES: Mitochondrial dysfunction has long been associated with the pathogenesis of lung cancer (LC). Mitochondrial DNA (mtDNA) haplogroups have been reported to modify the risk of LC in a few different populations; however, no study has been done among the Indians. Here, we explore the relationship between mtDNA haplogroups and LC in a representative eastern Indian sample set. METHODS: Different combinations of six mtDNA SNPs, which define the major Asian mtDNA haplogroups M and N, and their sub-haplogroups D, G, M7, R, and F were genotyped via polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) - sequencing approach in 94 smoker LC patients and 100 healthy smoker controls from an eastern Indian cohort. RESULTS: The distribution of 7 mtDNA haplogroups did not show any significant differences between patients and controls (p<0.05). We did not find sub-haplogroup M7 in our study population. CONCLUSIONS: Our study is the first to indicate that the major Asian mtDNA haplogroups have no significant (p<0.05) association with LC in East Indian population.

Prospective Observational Comparative Study of Response and Toxicities in Early Glottic Cancer Using Telecobalt Versus 3D-CRT.

The study was performed with 50 patients, 24 patients in Arm A and 26 patients in Arm B. Arm A-Conventional Telecobalt RT 66 Gy/33 fraction in stage T1N0M0 and stage T2N0M0 and Arm B-3D-CRT 66 Gy/33 fraction in T1N0M0 and T2N0M0 used. At the end of RT, 6 weeks, 3 months acute and late toxicities were noted by RTOG/EORTC morbidity scoring criteria for skin reaction, dysphagia and laryngeal toxicity. Fiber optic Laryngoscopy clinical assessment criteria were used to assess response after 6 weeks, 3 months of treatment completion. At 6 weeks of follow-up-Both Arm A and B complete response rate were 83.3% and 88.5% respectively and at 3 months rate were 85.0% and 95.7% respectively. There was no superiority of results with 3D-CRT over 2DRT. At the end of RT dysphagia grade 3 toxicity seen 1 patient (4.2%) but in Arm B (total 26 patients) no grade 3 toxicity found. At the end of 6 week and 3 month, one patient (4.3%) had grade 3 toxicity on Arm B only at 3 month. All these results are comparable. At the end of RT, one patient (3.8%) had incidentally dermatitis grade 3 toxicity in Arm B only. But all the results are comparable. On follow up, 6 week and 3 months, no grade 3 toxicity noted. At the end of RT, grade 3 laryngeal toxicity noted in 3 (12.5%) in Arm A and 2 (7.7%) in Arm B, not statistically significant. At 6 week, grade 3 toxicity found in 3/24 (12.5%) in Arm A and 2/26 (7.7%) in Arm B, at 3 months, 1/26 (4.3%) patient had incidental grade 3 toxicity only in Arm B. As conformal radiotherapy is more time consuming, less available in India and more costly than 2DRT, we can consider Conventional 2D planning for patients in India where most of people belong to low economic profile. Due to limitation in sample size and long-term follow-up further randomized studies are needed to validate the results.

Theory of mind deficit in women with breast cancer and depression: A comparative study.

Background: Studies have established that Theory of Mind (ToM) is impaired in patients with depression, but few studies have investigated the status of ToM in breast cancer patients who often suffer from depression. Our objective was to compare the ToM deficits in women with breast cancer with and without depression with a control group. Methods: The study was conducted at the Oncology department of a multi-speciality hospital in Kolkata. It was a cross sectional matched control study. We compared the ToM performance of women with breast cancer and depression (N=39), breast cancer without depression (N=63) and a healthy control group (N=34) using the widely used ToM task, Reading the Mind in the Eyes test (Eyes Test). Depression was diagnosed using Mini - International Neuropsychiatric Interview following International Classification of Diseases - 10th edition guidelines. Chi-square and one-way analysis of variances was done. Results: Both groups of patients had greater impairment in ToM compared to healthy controls (p<0.05). Among breast cancer patients, presence of depression predicted even greater impairment of ToM (p<0.05). Lower income, less education and not being in any occupation other than homemaking were associated with greater ToM impairment across all groups (p <0.05). Conclusion: Breast cancer patients suffering from depression may have an additional burden of impaired social cognition, which may reduce their ability to shore up social support when it is most required. This needs to be addressed urgently to ensure better quality of life.

A rare synchronous presentation of double primary malignancies - lung and prostate.

Synchronous (SC) diagnosis of double primaries is not very rare in this era of advanced technology where underlying malignancies can easily be detected by the modern imaging techniques. However, the treatment of such patients is quite challenging and often a therapeutic dilemma. A 74-year-old male smoker with no significant past or family history, presented with cough, hemoptysis, and difficulty in voidance of urine within 1 month of each other, i.e., SC presentation. Abnormalities were detected on the clinical examination and radiological imaging in the lung and prostate, which confirmed to be double primary malignancies of different histology on histopathology and immunohistochemistry, i.e., adenocarcinoma prostate and squamous cell carcinoma of the right lung.

A comprehensive meta-analysis and a case-control study give insights into genetic susceptibility of lung cancer and subgroups.

Reports of genetic association of polymorphisms with lung cancer in the Indian subcontinent are often conflicting. To summarise and replicate published evidence for association with lung cancer and its subgroups. We performed a meta-analysis of candidate associations on lung cancer, its histological subtypes and smoking status in the Indian subcontinent following PRISMA guidelines. Multiple testing corrections were done by the Benjamini-Hochberg method through assessment of significance at a false discovery rate of 10%. We genotyped and investigated rs1048943/CYP1A1 in a case-control sample from eastern India, followed by its global meta-analysis using a similar protocol. Meta-analysis of 18 variants of 11 genes reported in 39 studies (7630 cases and 8169 controls) showed significant association of rs1048943/CYP1A1 [2.07(1.49-2.87)] and rs4646903/CYP1A1 [1.48(1.93-1.95)] with overall lung cancer risk at 10% FDR, while nominal association (p < 0.05) was observed for del1/GSTT1, del2/GSTM1, rs1695/GSTP1 and rs17037102/ DKK2. Subtype analysis showed a significant association of del1/GSTT1 with adenocarcinoma, rs4646903/CYP1A1 with squamous carcinoma, and rs1048943/CYP1A1 with both. Association of rs4646903/CYP1A1 in smokers and effect modification by meta-regression analysis was observed. Genotyping of rs1048943/CYP1A1 that presented significant heterogeneity (p < 0.1) revealed an association with adenocarcinoma among eastern Indian smokers, while a global meta-analysis in 10458 cases and 10871 controls showed association with lung cancer and its subgroups. This study identified the susceptibility loci for lung cancer and its covariate-subgroups.

Choroidal melanoma of left eye with very early liver metastasis.

Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is 5-7 months. We report here a rare case of choroidal melanoma in a 45-year-old male smoker presented with liver metastasis within just 8 months after completion of initial treatments consists of enucleation of eye and 3 Dimensional conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease.

Primary synovial sarcoma of lung.

A synovial sarcoma (SS) is a rare form of cancer which usually occurs near the joints of the arm, neck, or leg, but has been documented in most human tissues and organs, including the brain, prostate, and heart. Primary pulmonary SS is an extremely rare tumor. We report a case of primary SS of lung who presented with severe chest pain and a large right lung mass with right-sided pleural effusion in computed tomography (CT) scan of thorax. The diagnosis was made on the basis of CT-guided core biopsy and immunohistochemistry. On immunohistochemistry, tumor cell expressed epithelial membrane antigen, bcl 2, Vimentin and smooth muscle actin and were immunonegative for S100 and cytokeratin. So, the final diagnosis was primary SS.