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Abstract: Objective: Matrix metalloproteinases (MMPs) are expressed in melanocytes and their overexpression has been linked to tumor development, progression, and metastasis. At the genetic level, following functional promoter polymorphisms are known to modify the gene transcription: −1306 C > T, −735 C > T in MMP2, and 799 C > T in MMP8 gene. Hence we hypothesize that functional polymorphisms in the 2 MMP SNPs in promoter region may modulate the risk for bladder cancer (BC) progression in North Indian population. Materials and methods: Genotyping for these polymorphisms were done in a group of 200 BC and 200 age matched, similar ethnicity unrelated healthy controls using PCR-based methods. Two-sided χ2, Cox-regression was utilized to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known BC confounders such as age and gender. Survival analysis was done using the Kaplan-Meier method and differences in survival were assessed using the log rank test. Results: Individuals with MMP2 (−1306) TT genotype as well as T allele were at higher risk of BC (P, 0.042; OR, 2.85; P, 0.001; OR, 1.76). This effect was even more apparent in case of CT+TT (P < 0.001; OR, 2.61). In MMP2 (735), CT+TT demonstrated significant risk (P, 0.034; OR, 1.66). In MMP8 (799), reduced risk was observed with TT genotype (P, 0.006; OR, 0.27). Haplotype analysis showed that individuals with haplotype 735C-1306T and 735T-1306C were at 1.9- and 1.5-fold higher risk. MMP2 −1306CC in combination with MMP8 799CT genotype showed protective effect. The genotype CT and CT+TT of MMP2 1306C > T were associated with high risk of recurrence in BCG treated patients (HR, 4.32; P, 0.006 and HR, 2.06; P, 0.047) thus showing reduced recurrence free survival (CT+TT/CC = 34/45 months; log rank P, 0.039). Conclusion: Our data suggested that variant allele of MMP2 1306C > T was associated with high risk of tumor recurrence and reduced recurrence free survival in superficial BC patients. [Copyright &y& Elsevier]

Background and Aims: Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity. We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism (SNPs) like TLR2 (−196 to−174del), TLR3 (C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes in patients with bladder cancer in a North Indian population. Methods: SNPs were comprised of TLR2 (−196 to −174 Del), TLR3(C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes. Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer (n = 200) and unrelated healthy controls of similar ethnicity (n = 200) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Results: In TLR2 I/D gene polymorphism, the combination of ID+DD showed a significant 3-fold increased risk (p = 0.001). TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype (ID+DD) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer. The other genotypes of TLR3, 4 and 9 did not exhibit any significant association with bladder cancer risk. Conclusions: Our results suggested the involvement of TLR2 (−196 to−174 del) in bladder cancer susceptibility; however, TLR3, 4 and 9 genes were not associated with risk of bladder cancer, implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer. [Copyright &y& Elsevier]

Schizophrenia is a severe psychiatric disorder with lifetime prevalence of ~ 1% worldwide. A genotyping study was conducted using a custom panel of Illumina 1536 SNPs in 840 schizophrenia cases and 876 controls (351 patients and 385 controls from North India; and 436 patients, 401 controls and 143 familial samples with 53 probands containing 37 complete and 16 incomplete trios from South India). Meta-analysis of this population of Indo-European and Dravidian ancestry identified three strongly associated variants with schizophrenia: STT3A (rs548181, p = 1.47 × 10 − 5 ), NRG1 (rs17603876, p = 8.66 × 10 − 5 ) and GRM7 (rs3864075, p = 4.06 × 10 − 3 ). Finally, a meta-analysis was conducted comparing our data with data from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ) that supported rs548181 ( p = 1.39 × 10 − 7 ). In addition, combined analysis of sporadic case–control association and a transmission disequilibrium test in familial samples from South Indian population identified three associations: rs1062613 ( p = 3.12 × 10 − 3 ), a functional promoter variant of HTR3A ; rs6710782 ( p = 3.50 × 10 − 3 ), an intronic variant of ERBB4 ; and rs891903 ( p = 1.05 × 10 − 2 ), an intronic variant of EBF1 . The results support the risk variants observed in the earlier published work and suggest a potential role of neurodevelopmental genes in the schizophrenia pathogenesis. [ABSTRACT FROM AUTHOR]