Microbes in gynecologic cancers: Causes or consequences and therapeutic potential.

Gynecologic cancers, starting in the reproductive organs of females, include cancer of cervix, endometrium, ovary commonly and vagina and vulva rarely. The changes in the composition of microbiome in gut and vagina affect immune and metabolic signaling of the host cells resulting in chronic inflammation, angiogenesis, cellular proliferation, genome instability, epithelial barrier breach and metabolic dysregulation that may lead to the onset or aggravated progression of gynecologic cancers. While microbiome in gynecologic cancers is just at horizon, certain significant microbiome signature associations have been found. Cervical cancer is accompanied with high loads of human papillomavirus, Fusobacteria and Sneathia species; endometrial cancer is reported to have presence of Atopobium vaginae and Porphyromonas species and significantly elevated levels of Proteobacteria and Firmicutes phylum bacteria, with Chlamydia trachomatis, Lactobacillus and Mycobacterium reported in ovarian cancer. Balancing microbiome composition in gynecologic cancers has the potential to be used as a therapeutic target. For example, the Lactobacillus species may play an important role in blocking adhesions of incursive pathogens to vaginal epithelium by lowering the pH, producing bacteriocins and employing competitive exclusions. The optimum or personalized balance of the microbiota can be maintained using pre- and probiotics, and fecal microbiota transplantations loaded with specific bacteria. Current evidence strongly suggest that a healthy microbiome can train and trigger the body's immune response to attack various gynecologic cancers. Furthermore, microbiome modulations can potentially contribute to improvements in immuno-oncology therapies.

Genetic Variant XRCC1 rs1799782 (C194T) and Risk of Cancer Susceptibility in Indian Population: A Meta-analysis of Case-Control Studies.

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. Several studies have reported contradictory results for XRCC1 exon 6 C>T (rs1799782) gene polymorphism and cancer risk in Indian population has provided inconsistent results. Therefore, we have performed this meta-analysis to evaluate the relationship between XRCC1 exon 6 C>T gene polymorphism and risk of cancer by published studies. We searched PubMed and Google scholar web databases to cover all studies published on association between XRCC1 exon 6 C>T gene polymorphism and cancer risk. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. In order to derive a more precise estimation of the association, A total of 3197 confirmed cancer cases and 3819 controls were included from eligible seventeen case-controls studies. Results from overall pooled analysis demonstrated suggested that that variant allele (T vs. C: OR 1.301, 95% CI 1.003-1.688, p = 0.047) was associated with the risk of overall cancer. Other genetic models; heterozygous (TC vs. CC: OR 1.108, 95% CI 0.827-1.485, p = 0.491), homozygous (TT vs. CC: OR 1.479, 95% CI 0.877-2.493, p = 0.142), dominant (TT+TC vs. CC: OR 1.228, 95% CI 0.899-1.677, p = 0.196) and recessive (TT vs. TC+CC: OR 1.436, 95% CI 0.970-2.125, p = 0.071) did not reveal statistical association. Publication bias observation was also considered and none was detected during the analysis. The present meta-analysis suggested that the variant allele T of XRCC1 exon 6 gene polymorphism was associated with the risk of cancer. It is therefore pertinent to confirm this finding in a large sample size to divulge the mechanism of this polymorphism and cancer risk in Indian population.

Bioengineered intravaginal isolate of Lactobacillus plantarum expresses algal lectin scytovirin demonstrating anti-HIV-1 activity.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.

Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases.

BACKGROUND: Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. METHODS: We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. RESULTS: We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. CONCLUSION: Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Polymorphic Variation in Double Strand Break Repair Gene in Indian Population: A Comparative Approach with Worldwide Ethnic Group Variations.

DNA repair capacity is essential in maintaining cellular functions and homeostasis. Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. Double strand break repair pathway plays critical roles in maintaining genome stability. Present study was conducted to determine distribution of XRCC3 Exon 7 (C18067T, rs861539) and XRCC7 Intron 8 (G6721T, rs7003908) gene polymorphisms in North Indian population and compare with different populations globally. The genotype assays were performed in 224 normal healthy individuals of similar ethnicity using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allelic frequencies of wild type were 79% (C) in XRCC3 Exon 7 C > T and 57% (G) in XRCC7 Intron 8 (G > T) 57% (G) observed. On the other hand, the variant allele frequency were 21% (T) in XRCC3 Exon 7 C > T and 43% (T) in XRCC7 Intron 8 G > T respectively. Major differences from other ethnic populations were observed. Our results suggest that frequency in these DNA repair genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis.

The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G > C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p < 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G > C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G > C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.

Tumor necrosis factor (TNF)-α -308G/A (rs1800629) polymorphism distribution in North India and its association with pemphigus: Case-control study and meta-analysis.

Pemphigus is an autoimmune blistering disorder of skin and/or mucosal surfaces characterized by intraepithelial lesions and immunoglobulin-G autoantibodies against desmogleins (proteins critical in cell-to-cell adhesion). Genetic, immunological, hormonal, and environmental factors are known to contribute to its etiology. Tumor necrosis factor-alpha (TNF-α) which plays a key role in pathogenesis of many infectious and inflammatory diseases has been found in high levels in lesional skin and sera of pemphigus patients. However, studies on association of single nucleotide polymorphism (SNP) in promoter region of TNF-α at position -308 affecting G to A transition with pemphigus has been scarce. This study was conducted to evaluate the TNF-α -308G/A SNP distribution in North Indian cohort, and to define the association between the TNF-α -308G/A SNP distribution and pemphigus, globally, by means of meta-analysis. TNF-α -308G/A SNP in pemphigus patients was investigated by cytokine genotyping using genomic DNA by PCR with sequence-specific primers. Meta-analysis of the data, including four previously published studies from other populations, was performed to generate a meaningful relationship. The results of our case-control study indicate non-significant differences between patients and controls in TNF-α -308G/A SNP. The meta-analysis also revealed that TNF-α -308G/A SNP is not associated with pemphigus risk in population at large; however, it may be contributing towards autoimmune phenomenon in pemphigus by being a part of its multi-factorial etiology. This study provides evidence that the TNF-α -308G/A polymorphism is not associated with overall pemphigus susceptibility. Nevertheless, further studies on specific ethnicity and pemphigus variants are necessary to validate the findings.

Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population.

The PTPN22 1858C/T polymorphism is associated with rheumatoid arthritis (RA). However, reports from the Asian populations are conflicting in nature and lacks consensus. The aim of our study was to evaluate the association between the PTPN22 1858C/T polymorphism and RA in Asian and Caucasian subjects by carrying out a meta-analysis of Asian and Caucasian data. A total of 27 205 RA cases and 27 677 controls were considered in the present meta-analysis involving eight Asian and 35 Caucasian studies. The pooled odds ratios (ORs) were performed for the allele, dominant, and recessive genetic model. No statistically significant association was found between the PTPN22 1858C/T polymorphism and risk of RA in Asian population (allele genetic model: OR = 1.217, 95% confidence interval (CI) = 0.99-1.496, p value 0.061; dominant genetic model: OR = 1.238, 95% CI = 0.982-1.562, p value 0.071; recessive genetic model: OR = 1.964, 95% CI = 0.678-5.693, p value 0.213). A significant association with risk of RA in Caucasian population suggesting that T-- allele does confer susceptibility to RA in this subgroup was observed (allele genetic model: OR = 1.638, 95% CI = 1.574-1.705, p value < 0.0001; dominant genetic model: OR = 1.67, 95% CI = 1.598-1.745, p value < 0.0001; recessive genetic model: OR = 2.65, 95% CI = 2.273-3.089, p value < 0.0001). The PTPN22 1858C/T polymorphism is not associated with RA risk in Asian populations. However, our meta-analysis confirms that the PTPN22 1858C/T polymorphism is associated with RA susceptibility in Caucasians.

Meta-analysis Reveals No Association of DNMT3B -149 C>T Gene Polymorphism With Overall Cancer Risk.

BACKGROUND: DNA methyltransferase-3B (DNMT3B) plays a key role in establishment and maintenance of genomic methylation patterns. Polymorphism in promoter region -149 C>T (C46359T) of DNMT3B gene may alter DNMT3B activity which leads to increased susceptibility to cancer. Inconsistent results regarding this have been reported in a number of studies. OBJECTIVE: To carry out a meta-analysis of the studies reported to assess the precise relationship between the DNMT3B -149 C>T polymorphism and the overall cancer risk. METHOD: PubMed (MEDLINE) web database was searched for the studies concerning DNMT3B -149 C>T polymorphism and its association with cancer risk. The pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated for all the genetic models, from the selected case-control studies, by meta-analysis. RESULTS: Overall eighteen studies containing 5583 cancer cases and 7618 controls were analyzed. No significant risk was observed overall for T allele carrier (T vs. C: p=0.303; OR=1.032, 95% CI=0.972-1.097), homozygous (TT vs. CC: p=0.336; OR=1.063, 95% CI=0.939-1.204), heterozygous (CT vs. CC: p=0.802; OR=1.022, 95% CI=0.860-1.216), dominant (TT vs. CC+CT: p=0.298; OR=1.101, 95% CI=0.919-1.319) and recessive (TT+CT vs. CC: p=0.656; OR=1.021, 95% CI=0.931-1.121) genetic models. Subgroup analysis of Asian and Caucasian populations also did not demonstrate any cancer risk in all the genetic models studied. CONCLUSION: Our meta-analysis proposes that the DNMT3B -149 C>T polymorphism may not be an independent predisposing factor for the risk of cancer. However, larger sample size and expression studies are required to confirm the observation.

No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis.

BACKGROUND: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. MATERIALS AND METHODS: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. RESULTS: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. CONCLUSIONS: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.

Prevalence of drug resistance in clinical isolates of tuberculosis from GCC: a literature review from January 2002 to March 2013.

INTRODUCTION: The prevalence of drug resistance in clinical isolates of Mycobacterium tuberculosis from the Gulf Cooperation Council (GCC; Saudi Arabia, Qatar, Bahrain, Kuwait, Oman, United Arab Emirates [UAE]) countries was appraised using reports published between January 2002 and March 2013. METHODOLOGY: A total of 11,393 tuberculosis (TB) isolates from the GCC were studied through published literature and were analyzed statistically. RESULTS: Most of the isolates were resistant to isoniazid, followed by streptomycin, rifampin, ethambutol, and pyrazinamide. The highest prevalence rate of multidrug-resistant-TB (MDR-TB) was found in UAE (9.2%), followed by Kuwait (5.9%) and Saudi Arabia (4.3%). The overall MDR-TB prevalence rate was recorded as 4.0% in the entire GCC region. Automated linear modeling revealed that isoniazid resistance had a strong relationship with the prevalence of MDR-TB in all the GCC countries and was found to be the strongest predictor for MDR-TB. Interestingly, rifampicin resistance was significantly associated with the prevalence of MDR-TB in Oman, Kuwait, and Saudi Arabia, while isoniazid was identified for UAE. On the basis of a number of reports and isolates, the principal component analysis showed that, among all GCC member countries, the highest burden of TB was in Saudi Arabia and Kuwait, and maximum drug resistance was present in UAE. CONCLUSION: The study demonstrates that the prevalence of MDR-TB in GCC countries is almost equal to other developing and developed countries, and requires immediate attention for surveillance and control.

Significance of impaired serum gelatinases activities in metabolic syndrome.

INTRODUCTION: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. MATERIALS AND METHODS: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control. RESULTS: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. CONCLUSIONS: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Vitamin D receptor ApaI gene polymorphism and tuberculosis susceptibility: a meta-analysis.

AIM: Vitamin D performs its actions through the vitamin D receptor (VDR), which acts as a transcriptional factor. Many case-control studies have been performed in the past to elucidate the association of the ApaI polymorphism of VDR gene and the risk of tuberculosis (TB). However, these studies have shown inconsistent and conflicting results. In the present study, a meta-analysis was performed to investigate the potential relationship between the VDR ApaI gene polymorphism and the risk of TB. METHODOLOGY: A quantitative synthesis was performed for the published studies based on the association between the VDR ApaI gene polymorphism and the risk of TB retrieved from PubMed (Medline) and EMBASE web databases. A meta-analysis was performed, and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models. RESULTS: We observed a decreased risk of TB in allelic contrast (a vs. A: p=0.009; OR=0.869, 95% CI=0.782 to 0.965), homozygous (aa vs. AA: p=0.006; OR=0.724, 95% CI=0.575 to 0.910), and heterozygous (aA vs. AA: p=0.698; OR=0.948, 95% CI=0.722 to 1.243) comparisons. Similarly, dominant (aa+Aa vs. AA: p=0.032; OR=0.842, 95% CI=0.720 to 0.985) and recessive (aa vs. AA+Aa: p=0.027; OR=0.796, 95% CI=0.650 to 0.975) models also demonstrated a decreased risk of TB, whereas a heterozygous genotype (Aa vs. AA: p=0.109; OR=0.873, 95% CI=0.740 to 1.030) did not indicate any association with the risk of TB. There was no evidence of publication bias and heterogeneity test. CONCLUSIONS: This meta-analysis suggests that ApaI polymorphism of the VDR gene is significantly associated with a decreased risk of TB. However, future larger studies with groups of populations are warranted to analyze this association.

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population.

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172-1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280-2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215-1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244-1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151-1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene-gene and gene-environment interactions are required.

Insertion/deletion polymorphism of the ACE gene increased risk of Behcet disease: evidence from a meta-analysis.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction has a role in the development of the Behcet disease (BD). Local renin-angiotensin system (RAS) plays a crucial role in the endothelial control, and angiotensin-converting enzyme (ACE) is the monitoring component of the RAS. We investigated the relationship between the ACE Ins/Del (I/D) variants and the risk of BD. DESIGN AND SETTINGS: A meta-analysis was conducted from all published studies on the associations be.tween the ACE I/D polymorphism and BD. METHODS: We systemically searched all published studies from PubMed and EMBASE, and data were quantitatively synthesized. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele, homozygous, heterozygous, and combined genetic models. RESULTS: Out of 5 eligible studies, 676 healthy controls and 534 BD cases were included in the present meta.analysis. D allele carrier was significantly associated with increased BD risk (D vs I: P=.002; OR=1.321, 95% CI=1.111-1.570). Homozygous mutant DD genotype also revealed 1.5-fold increased risk (DD vs II; P=.004; OR=1.573, 95% CI=1.156-2.141). In addition, the dominant genetic model demonstrated an increased risk of developing BD (DD vs II+ID: P=.001; OR=1.610, 95% CI=1.242-2.087). CONCLUSION: The current study suggests that ACE gene polymorphism (Ins/Del) contributes an increased susceptibility to BD. However, larger studies with stratified case control population and biological characterization are needed to validate this finding.

Vascular endothelial growth factor 936 c>T polymorphism increased oral cancer risk: evidence from a meta-analysis.

AIM: The vascular endothelial growth factor (VEGF) plays a major role in angiogenesis. The association between VEGF 936 C>T (rs3025039) gene polymorphisms and oral cancer (OC) risk is still contentious and ambiguous. To assess the relationship between the VEGF 936 C>T genotype and the risk of developing OC, we performed a meta-analysis to summarize the possible association. METHODOLOGY: We assessed published studies of the association between 936 C>T polymorphisms and OC risk from four studies with 440 controls and 556 OC cases. We calculated pooled odds ratios (ORs) and 95% confidence interval (CI), considering the frequency of allele, homozygous, heterozygous genotypes and comparison of dominant and recessive genetic models. RESULTS: The combined results showed that the T allele was significantly associated with increased OC risk (T vs. C: p=0.001; OR=1.521, 95% CI=1.194-1.938). The heterozygous genotype CT had a 1.5-fold increased risk (CT vs. CC: p=0.002; OR=1.582, 95% CI=1.184-2.114). In addition the dominant genetic model demonstrated a 1.6-fold increased risk of developing OC (TT+CT vs. CC: p=0.001; OR=1.621, 95% CI=1.226-2.143). CONCLUSION: Our results suggest that the VEGF gene polymorphism (936 C>T) contributes increased susceptibility to OC. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.

Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population?

OBJECTIVE: Prostate cancer (CaP) is a heterogeneous, multifactorial, and multifocal disease. Therefore, the search for a combination of functional polymorphisms using cell cycle and apoptotic genes as tumor markers is fundamental for a more precise and reliable diagnosis. In the present study, we investigated the diagnostic value of 3 different genes associated with CaP carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes that are differentially expressed in CaP. METHODS: In a hospital-based case control study of northern India, blood samples were obtained from 192 CaP patients and 224 cancer-free age matched unrelated healthy controls of similar ethnicity. They were genotyped for MDM2 G309T, CCND1 G870A, Fas A670G, and G1377A polymorphisms using polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: MDM2 309GG variant was at reduced risk for developing CaP (P = 0.041; OR, 0.59). Whereas CCND1 AA genotype demonstrated increased risk (P = 0.018; OR, 1.86). The diplotype analysis of Fas G670A and G1377A (G-A) was observed to be associated with a significant increase in CaP risk (P = 0.024; OR, 1.63). CONCLUSION: Findings based on current sample size our results suggested a positive association of CCND1AA genotype and diplotype analysis of Fas G670A and G1377A (G-A) to be associated with CaP risk that could influence the pathophysiology, thereby modulating the risk of CaP.

Base excision repair pathway genes polymorphism in prostate and bladder cancer risk in North Indian population.

PURPOSE: Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers. METHODS: This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C>T), 9 (G>A), 10 (G>A), OGG1 Exon 7 (C>G) and APE1 Exon 5 (T>G) genes polymorphism using PCR-RFLP and ARMS. RESULTS: GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p=0.001; p=0.006). Similarly variant containing genotype revealed association with PCa (p=0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR=0.25; p=0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p=0.028). CONCLUSIONS: Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.