Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation.

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing 'fit-for-use' diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Thr@ee-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings. Interpretation & conclusions: Diagnostics developed using these TPPs will facilitate utilization of invested resources leading to development of the products that have potential to ease the economic burden on patient and save lives.

Ethical Cultures in Perinatal Care: Do They Exist? Correlation of Provider Attitudes with Periviability Practices at Six Centers.

OBJECTIVE: This study aimed to compare attitudes of providers regarding perinatal management and outcomes for periviable newborns of caregivers at centers with higher resuscitation (HR) and lower resuscitation (LR) rates in the delivery room. STUDY DESIGN: All obstetric and neonatal clinical providers at six U.S. sites were invited to complete an anonymous online survey. Survey responses were compared with clinical data collected from a previous retrospective study comparing centers' rates of planned resuscitation. Responses were analyzed by multivariable logistic and linear regression to assess how HR versus LR center respondents differed in management preferences and outcome predictions. RESULTS: Paradoxically, HR versus LR respondents, when adjusting for other variables, were less likely to respond that interventions such as antenatal steroids (odds ratio: 0.61, 95% confidence interval [CI]: 0.42-0.88, p < 0.009) and resuscitation (OR: 0.59, 95% CI: 0.44-0.78, p < 0.001) should be given at 22 weeks. HR versus LR respondents also reported lower likelihood of survival and acceptable quality of life (OR: 0.7, 95% CI: 0.53-0.93, p = 0.012) at 23 weeks. CONCLUSION: Despite higher rates of planned resuscitation at 22 and 23 weeks, steroid usage and survival rates did not differ between HR and LR sites. In this subsequent survey, respondents from HR centers had a less favorable outlook on interventions for these newborns than those at LR centers, suggesting that instead of driving practices, attitudes may be more closely associated with experiences of clinical outcomes.

Purine Metabolite Signatures and Type 2 Diabetes: Innocent Bystanders or Actionable Items?

PURPOSE OF REVIEW: This article reviews evidence linking cardiometabolic conditions with changes in purine metabolites, including increased serum uric acid (sUA), and discusses intervention studies that investigated the therapeutic relevance of these associations. RECENT FINDINGS: Metabolic and epidemiological findings support a correlation between sUA and circulating levels of other purines with insulin resistance (IR) and risk factors for cardiovascular disease (CVD). In addition, increased activity of xanthine oxidoreductase (XOR), the rate-limiting enzyme for UA production, has been detected in tissues targeted by obesity. Yet, inhibition of XOR in pre-clinical and clinical studies generally failed to support a causal role for excess sUA in IR and CVD. The lack of efficacy of XOR inhibitors strongly suggests that UA is a marker of, rather than a direct contributory factor for, cardiometabolic diseases. Validation of the function of other purines will require a paradigm shift, from a "UA-centric" view to a more granular assessment of the entire purine network and its interaction with other pathways.

Antenatal Periviability Counseling and Decision Making: A Retrospective Examination by the Investigating Neonatal Decisions for Extremely Early Deliveries Study Group.

OBJECTIVE: To describe periviability counseling practices and decision making. STUDY DESIGN: This is a retrospective review of mothers and newborns delivering between 22 and 24 completed weeks from 2011 to 2015 at six U.S. centers. Maternal and fetal/neonatal clinical and maternal sociodemographic data from medical records and geocoded sociodemographic information were collected. Separate analyses examined characteristics surrounding receiving neonatology consultation; planning neonatal resuscitation; and centers' planned resuscitation rates. RESULTS: Neonatology consultations were documented for 40, 63, and 72% of 498 mothers delivering at 22, 23, and 24 weeks, respectively. Consult versus no-consult mothers had longer median admission-to-delivery intervals (58.7 vs. 8.7 h, p < 0.001). Consultations were seen more frequently when parental decision making was evident. In total, 76% of mothers had neonatal resuscitation planned. Resuscitation versus no-resuscitation newborns had higher mean gestational ages (24.0 vs. 22.9 weeks, p < 0.001) and birthweights (618 vs. 469 g, p < 0.001). Planned resuscitation rates differed at higher (HR) versus lower (LR) rate centers at 22 (43 vs. 7%, p < 0.001) and 23 (85 vs. 58%, p < 0.001) weeks. HR versus LR centers' populations had more socioeconomic hardship markers but fewer social work consultations (odds ratio: 0.31; confidence interval: 0.15-0.59, p < 0.001). CONCLUSION: Areas requiring improvement included delivery/content of neonatology consultations, social work support, consideration of centers' patient populations, and opportunities for shared decisions.

Integrated genome-wide analysis of genomic changes and gene regulation in human adrenocortical tissue samples.

To gain insight into the pathogenesis of adrenocortical carcinoma (ACC) and whether there is progression from normal-to-adenoma-to-carcinoma, we performed genome-wide gene expression, gene methylation, microRNA expression and comparative genomic hybridization (CGH) analysis in human adrenocortical tissue (normal, adrenocortical adenomas and ACC) samples. A pairwise comparison of normal, adrenocortical adenomas and ACC gene expression profiles with more than four-fold expression differences and an adjusted P-value < 0.05 revealed no major differences in normal versus adrenocortical adenoma whereas there are 808 and 1085, respectively, dysregulated genes between ACC versus adrenocortical adenoma and ACC versus normal. The majority of the dysregulated genes in ACC were downregulated. By integrating the CGH, gene methylation and expression profiles of potential miRNAs with the gene expression of dysregulated genes, we found that there are higher alterations in ACC versus normal compared to ACC versus adrenocortical adenoma. Importantly, we identified several novel molecular pathways that are associated with dysregulated genes and further experimentally validated that oncostatin m signaling induces caspase 3 dependent apoptosis and suppresses cell proliferation. Finally, we propose that there is higher number of genomic changes from normal-to-adenoma-to-carcinoma and identified oncostatin m signaling as a plausible druggable pathway for therapeutics.

Major Challenges and Potential Microenvironment-Targeted Therapies in Glioblastoma.

Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF-VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM. Potential combination therapies targeting the tumor microenvironment (TME) to overcome the myeloid cell-mediated resistance problem in GBM are discussed. Future directions are focused on the use of TME-directed therapies in combination with standard therapy in clinical trials, and the exploration of novel therapies and GBM models for preclinical studies. We believe this review will guide the future of GBM research and therapy.

A Narrative Overview of Coronavirus Infection: Clinical Signs and Symptoms, Viral Entry and Replication, Treatment Modalities, and Management.

The global pandemic known as coronavirus disease (COVID-19) is causing morbidity and mortality on a daily basis. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV--2) virus has been around since December 2019 and has infected a high number of patients due to its idiopathic pathophysiology and rapid transmission. COVID-19 is now deemed a newly identified "syndrome" condition since it causes a variety of unpleasant symptoms and systemic side effects following the pandemic. Simultaneously, it always becomes potentially hazardous when new variants develop during evolution. Its random viral etiology prevents accurate and suitable therapy. Despite the fact that multiple preclinical and research studies have been conducted to combat this lethal virus, and various therapeutic targets have been identified, the precise course of therapy remains uncertain. However, just a few drugs have shown efficacy in treating this viral infection in its early stages. Currently, several medicines and vaccinations have been licensed following clinical trial research, and many countries are competing to find the most potent and effective immunizations against this highly transmissible illness. For this narrative review, we used PubMed, Google Scholar, and Scopus to obtain epidemiological data, pre-clinical and clinical trial outcomes, and recent therapeutic alternatives for treating COVID-19 viral infection. In this study, we discussed the disease's origin, etiology, transmission, current advances in clinical diagnostic technologies, different new therapeutic targets, pathophysiology, and future therapy options for this devastating virus. Finally, this review delves further into the hype surrounding the SARS-CoV-2 illness, as well as present and potential COVID-19 therapies.

Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.

Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.

Interleukin-13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome-wide expression studies have demonstrated the overexpression of interleukin-13 receptor alpha2 (IL13Rα2) in some human malignancies. METHODS: The authors evaluated IL13Rα2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 Rα2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI-H295R [high IL13Rα2 expression] and SW13 [low IL13Rα2 expression]) to a highly specific IL-13 conjugated with Pseudomonas exotoxin (IL-13-PE) also was evaluated in both in vitro and in vivo models. RESULTS: IL13Rα2 was overexpressed in malignant tumors compared with benign and normal samples (15-fold higher; P < .05). Immunohistochemistry also confirmed higher protein expression in malignant and benign tumors than in normal adrenocortical tissues (P < .05). The half-maximal inhibitory concentration for IL-13-PE was 1.3 ng/mL in the NCI-H295R cell line and 1000 ng/mL in the SW13 cell line. Mice that received intratumoral or intraperitoneal IL-13-PE injection had a significant reduction in tumor size and increased tumor necrosis compared with control groups (P < .05) and also had prolonged survival (P < .05). IL13Rα2 protein expression increased in cells that were treated with IL-13 ligand along with cell invasion (P < .05). Direct IL13Rα2 knockdown decreased cellular proliferation and invasion (P < .05). CONCLUSIONS: The current results indicated that IL13Rα2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13Rα2 is a novel therapeutic target for the treatment of human ACC.

Molecular markers of adrenocortical tumors.

Adrenocortical tumors are common and incidentally discovered in up to 14% of axial imaging studies performed for other indications. Most of these tumors are nonfunctioning but may require removal because of the risk of adrenocortical carcinoma. Unfortunately, most clinical and imaging features are still not accurate enough to allow definitive diagnosis and an increasing number of patients undergo adrenalectomy to exclude a cancer diagnosis. Adrenocortical carcinoma is an aggressive malignancy with no effective therapy for patients with locally advanced and metastatic disease. Studies using new genomic approaches including mRNA, miRNA, methylation, and CGH profiling have identified dysregulated genes and pathways that may have clinical implications in improved molecular diagnosis and prognostication of adrenocortical cancer (ACC). In this review, we highlight recent advances in the molecular diagnosis of adrenocortical tumors.

Immunotherapy for Breast Cancer Treatment: Current Evidence and Therapeutic Options.

Breast Cancer (BC) has the highest incidence among all forms of malignancies detected in women globally. The therapeutic approaches available for BC include chemotherapy, radiation therapy, hormonal therapy, and surgery. Recently, advanced immunology-based therapeutics with potential for BC treatment, including immune checkpoint blockades, vaccines, and combinations with other treatment strategies, have emerged. Although commonly used treatments such as trastuzumab/ pertuzumab for human epidermal growth factor receptor 2-positive BC and hormone therapy for estrogen receptor-positive and/or progesterone receptor-positive BC are specific, triple-negative BC cases remain a great challenge for treatment measures. Immune checkpoint inhibitors (anti- PD-1/anti-CTLA-4) and anti-cancer vaccines (NeuVax, MUC-1, AVX901, INO-1400, and CEA), either alone or in combination with other therapies, represent a new paradigm in cancer therapeutics. In this review, we highlight the current immunotherapeutic aspects and ongoing trials aimed at the development of better treatment regimens for BC.

Association of functionally important polymorphism of microsomal epoxide hydrolase gene (EPHX1) with lung cancer susceptibility.

Distribution and gene-environment interaction of EPHX1 polymorphism was evaluated in 175 lung cancer patients and 322 controls from north India. Two novel non-synonymous, Lys117Arg and Leu263Phe, and twelve single nucleotide polymorphisms were identified in the present study. Binary logistic regression analysis showed association of polymorphism Tyr113His with increased risk of lung cancer (OR = 2.2, 95% CI = 1.2-4.0, p < .05). Gene-environment interaction revealed that patients with His113His and smoking habit had significantly greater risk of lung cancer (OR = 4.52, 95% CI = 0.93-43.05, p < .05). Present study provided evidence that EPHX1 polymorphism is associated with lung cancer susceptibility in Indian population.

Transplant-associated Thrombotic Microangiopathy Treated with Eculizumab and Romiplostim.

Transplant-associated thrombotic microangiopathy (TA-TMA) can occur after solid organ transplantation. It results in thrombocytopenia, haemolytic anaemia and microvascular occlusion. TA-TMA is not fully understood and treatment has not been clearly established. However, there is increasing evidence to suggest an immune-complement mediated component to its development. Eculizumab is a monoclonal antibody that inhibits the cleavage of C5 into pro-inflammatory, prothrombotic terminal complement elements and has been utilized in the treatment of atypical haemolytic uremic syndrome. We report a case of TA-TMA successfully treated with eculizumab and romiplostim. This case adds to the evidence that TA-TMA is triggered by complement dysregulation and suggests possible interventions for refractory cases. LEARNING POINTS: Transplant-associated thrombotic microangiopathy (TA-TMA) may occur in solid organ transplant patients.Eculizumab may be used for the treatment of TA-TMA.

Role of TGF-beta1 (-509C>T) promoter polymorphism in susceptibility to cervical cancer.

Transforming growth factor-beta (TGF-beta) family members are multifunctional cytokines that play a key role in cellular growth, proliferation, and differentiation. The aim of study was to evaluate the association of TGF-beta1 -509 C>T gene polymorphism with risk of cervical cancer. The study was carried out in 150 histopathology confirmed patients with cervical cancer and 162 cervical-cytology negative females. Polymorphisms for TGF-beta1 -509C>T gene was genotyped by polymerase chain reaction and restriction enzyme digestion. Frequencies of individuals with -509TT genotype and T allele of TGF-beta1 gene polymorphisms did not differ significantly in patients with cervical cancer and controls (p = 0.328, OR = 1.37 and p = 0.605, OR = 1.09). Cervical cancer patients with -509TT had marginal low risk for stage I (p = 0.04, OR = 0.95, 95% CI = 0.91-0.99) but -509TT genotype of TGF-beta1 was associated with increased risk of stage II of cancer (p = 0.07, OR = 3.13, 95% CI = 0.87-11.14). In gene-environment interaction, carriers of TGF-beta1 -509TT genotype with tobacco usage were at higher risk of cervical cancer (OR = 3.67, 95% CI = 0.38-35.1). In conclusion, our data suggest that TGF-beta1 -509T allele confers marginal protection for early stage 1B but risk for stage II of cervical cancer.

Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma.

Cyclooxygenase-2 (COX-2) influences carcinogenesis through regulation of angiogenesis, apoptosis and cytokine expression. We aimed to evaluate association of COX-2 polymorphisms with predisposition to esophageal squamous cell carcinoma (ESCC), its phenotype variability and modulation of environmental risk in northern Indian population. We genotyped 174 patients with ESCC and 216 controls for COX-2 gene polymorphisms (-765G>C; -1195G>A; -1290A>G; 3'UTR 8473T>C) using PCR-RFLP. Data were statistically analyzed using chi-square test and logistic regression model. COX-2 -765C allele carriers were at increased risk for ESCC (OR=1.66; 95% CI=1.08-2.54; P=0.004). However, -1195G>A; -1290A>G; 3'UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with ESCC. We observed significantly enhanced risk for ESCC due to interaction between COX-2 -1195GAx-765GC+CC genotypes (OR=4.60; 95% CI=1.63-13.01; P=0.004). High risk to ESCC was also observed with respect to COX-2 haplotypes, A(-1290)G(-1195)C(-765)T(8473) and A(-1290)A(-1195)C(-765)T(8473) [OR=3.35; 95% CI=0.83-13.44; P=0.089; OR=4.28; 95% CI=0.43-42.40; P=0.246] however, it was not statistically significant. Stratification of subjects based on gender showed that females were at higher risk for ESCC due to COX-2 -765C carrier genotypes (OR=2.97; 95% CI=1.23-7.18; P=0.016). In association of genotypes with clinical characteristics, -765C carrier genotype conferred risk of ESCC in middle third of esophagus (OR=1.78; 95% CI=1.08-2.93; P=0.023). In case-only analysis, interaction of environmental risk factors and COX-2 genotypes did not further modulate the risk for ESCC. In summary, COX-2 -765G>C polymorphism confers ESCC susceptibility particularly in females and patients with middle third anatomical location of the tumor. Interaction of COX-2 -1195GA and -765C carrier genotypes also modulates ESCC risk.

Association of TNFA (-308G>A) and IL-10 (-819C>T) promoter polymorphisms with risk of cervical cancer.

Etiology of cervical cancer is associated with excessive inflammation mediated tumorigenesis. Pro and anti-inflammatory cytokines (tumor necrosis factor alpha, TNFA and interleukin, IL-10) are involved in fighting against the tumorigenesis. Therefore, the present study was designed to evaluate the association of TNFA (-308G>A) and IL-10 (-819C>T) gene polymorphism with risk of cervical cancer. One hundred fifty histopathologically confirmed patients with cervical cancer and 162 age, ethnically-matched cervical cytology negative healthy controls were genotyped for TNFA (-308 G>A) and IL-10 (-819 C>T) polymorphisms using PCR-RFLP. Individuals with combination of TNFA -308GA+AA genotype and A allele were at elevated risk of cervical cancer (odds ratio (OR) = 2.24; P = 0.018 and OR, 2.05; P = 0.012). Frequency of IL-10 -819CT+TT genotype combination and T allele was slightly higher in cases as compared with controls but difference was not significant (OR = 1.52; P = 0.069 and OR = 1.38; P = 0.051). In association of genotypes with clinical characteristics, presence of TNFA -308GA+AA genotype conferred high risk for the stages (IB) (OR = 2.86, P = 0.039) and stages (III) (OR = 2.52; P = 0.015) of cervical cancer. In contrast, IL-10 -819TT genotype was not associated with higher risk of clinical characteristics of cervical cancer. In conclusion, individuals with TNFA -308*A allele carriers were at significantly higher risk of cervical cancer particularly early (IB) and advanced stages (III). However, IL-10 (-819C>T) polymorphism was not associated with risk of cervical cancer.

Characterization of Vibrio cholerae from deep ground water in a cholera endemic area in Central India.

A total of 8 out of 11 deep ground water samples collected from different villages in Central India were found contaminated with Vibrio cholerae non O1, non O139. In a multiplex PCR, isolates were found positive for ompW gene but negative for ctxAB and rfbO1 genes. However, isolates from two places were positive for tcp and zot genes, indicating their intestinal colonization and toxigenic potential. Antibiotic susceptibility studies revealed that all isolates were multidrug resistant. Although, none of the isolates was found PCR positive for the mobile genetic elements, class 1 integrons and SXT constins. The results of this study corroborated that deep ground water can also be an important reservoir of V. cholerae in plane endemic areas, suggesting a continuous monitoring of water samples for timely prevention of the disease.

Association of interleukin-6 (-174G>C) promoter polymorphism with risk of squamous cell esophageal cancer and tumor location: an exploratory study.

Chronic inflammation plays a role in transformation from normal cell to malignant state. Interleukin-6 (IL-6) regulates inflammation and various physiological processes. IL-6 promoter polymorphism (-174G>C) is associated with transcription differences in vitro and in vivo. High expression of IL-6 may result in oxidative DNA damage and enhance risk of carcinogenesis. Therefore, we aimed to evaluate association of IL-6 -174G>C polymorphism with predisposition to esophageal cancer (EC) in 369 subjects (168 patients with EC and 201 controls). We observed significant association of IL-6 -174C non-carrier genotype with risk of EC, (OR=2.29; P=0.001), with squamous cell carcinoma (SCC) histology (OR=2.26; P=0.001) and tumor at upper and lower anatomical locations (OR=5.97; P=0.009 and OR=2.34; P=0.034). Patients having IL-6 -174C non-carrier genotype were at elevated risk of metastasis (OR=2.49; P=0.005). In conclusion, IL-6 -174G>C gene polymorphism may confer high risk for EC and its clinical characteristics.

Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study.

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1 beta and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1 beta (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1 beta -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11-0.62; p = 0.002; OR = 0.462; 95% CI = 0.253-0.845, p = 0.01). In conclusion, subjects with IL-1 beta -511TT genotype or IL-1 beta*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.

MMP-7 (-181A>G) promoter polymorphisms and risk for cervical cancer.

OBJECTIVES: Matrix metalloproteinase (MMP-7) is a secreted matrilysin, which contributes to tumor progression through breakdown of basement membranes and angiogenesis. Therefore, we aimed to investigate the association of MMP-7 -181A>G gene polymorphism with risk of cervical cancer. METHODS: In the present case control study, we enrolled a total of 150 cervical cancer patients confirmed by histopathology and 162 unrelated healthy individuals. Polymorphism for MMP-7 gene (-181A>G) was genotyped by polymerase chain reaction and restriction enzyme length polymorphism. RESULTS: Frequency of MMP-7 -181GG genotype and -181G allele differed significantly between patients with cervical cancer (29.3%) and healthy individuals (19.4%) (P=0.041; OR(GG)=1.94 and P=0.048; OR(G)=1.94). Individuals with MMP-7 -181GG genotype were at higher risk of stage II of cervical cancer with borderline significance (P=0.05, OR=2.78; 95%CI: 0.89-8.69). However, interaction of MMP-7 -181AG and GG genotypes with tobacco usage did not modulate the cervical cancer risk significantly (OR 2.21, 95%CI=0.59-8.1 and OR 3.17, 95%CI=0.64-15.7). CONCLUSION: Individuals with MMP-7 -181GG genotype were at significantly higher risk of cervical cancer.