KRAS and BRAF genetic alterations in lung cancer: A case - control study.

CONTEXT: Lung cancer (LC) is one of the most critical neoplastic abnormalities, having globally a high mortality rate. Knowledge about its genetic mutations and their association with clinically pathological features of LC is very important. Here, we describe the epidemiological molecular study of genetic mutations in KRAS and BRAF genes and their relationship with the demographic and clinical characteristics of Pakistani patients with lung adenocarcinoma. AIM: To analyze the mutations of KRAS and BRAF in LC patients among Pakistani population. SETTINGS AND DESIGN: The study has been carried out at universities and health institutes of Islamabad, Pakistan. METHODS AND MATERIAL: Deoxyribonucleic acid (DNA) was extracted from the patient samples by using the standard protocol and amplified by using the specific primers. Later on, the Polymerase Chain Reaction (PCR) products were examined with the help of single stranded conformational polymorphism (SSCP). STATISTICAL ANALYSIS: Relationship between KRAS, BRAF mutations, and LC risk was accessed by conditional logistic regression using SPSS version 24.0. Results were illustrated by odds ratio (OR), 95% confidence interval (CI), and P value. RESULTS: LC is more common in male population and smoking is one of the leading risk factors for (p < 0.0001) LC. KRAS and BRAF mutations were found to be contributing factors toward LC development and showed statistically significant results along with conformation through computational analysis. CONCLUSIONS: It can be concluded that smoking is lethal and cancer causing. The concomitant mutations found in KRAS and BRAF were infrequent, and they probably have a very unusual effect on the clinical management of Pakistani patients with lung adenocarcinoma.

Therapeutic efficacy of Strobilanthes urticifolia-infused pectin/polyacrylic acid hydrogel for targeted hepatorenal fibrosis mitigation: A multifaceted biomaterial approach.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

A meta-analysis and experimental data for multidrug resistance genes in breast cancer.

Background: Increasing trend of breast cancer incidence worldwide is a known fact. This curable disease may become fatal if drug resistance is developed leading to metastatic cancerous tissue. Objective: This is a two parts study; a meta-analysis exploring association of drug resistance (mdr1 and ABCG2) genes with breast cancer and mutational association with molecular subtypes of cancer. Methods: PCR-SSCP for genomic polymorphisms and RT-PCR for expression analysis were performed. Results: C3435T polymorphism of mdr1 gene was most commonly studied mutation with contradictory results. Association of ABCG2 gene mutations with untreated breast cancer was reported only by one study so far. Regarding current genomic analysis of mdr1 gene, three novel mutations were found in exon 12 and 2 mutations were found in exon 26. In ABCG2 gene, addition of C and T were found in intron 8 at the intron-exon junction. A positive correlation was observed between these mutations and tumor grade. Levels of mRNA expression revealed that they were over expressed in cancerous tissues compared with controls. Conclusion: These findings suggest that these genes are associated with breast cancer.

Correlation of ERCC5 polymorphisms and linkage disequilibrium associated with overall survival and clinical outcome to chemotherapy in breast cancer.

Purpose: ERCC5 is a DNA endonuclease and nucleotide excision repair gene; its mutations lead to a lack of activity by this enzyme, causing oxidative DNA damage. This study aimed to assess the role of four selected single nucleotide polymorphisms (SNPs) in ERCC5 and their linkage disequilibrium associated with survival analysis and clinical outcomes in breast cancer. Patients and methods: Four SNPs (rs751402, rs17655, rs2094258, and rs873601) of the ERCC5 gene were analyzed using the PCR-RFLP technique, followed by sequencing in 430 breast cancer (BC) cases and 430 cancer-free individuals. Statistical analysis was performed using MedCalc 17 and SPSS version 24, while bioinformatic analysis of linkage disequilibrium was performed using Haploview software 4.2. Results: Multivariate analysis showed that the rs751402 and rs2094258 polymorphisms were significantly associated with an elevated risk of BC (P < 0.001), while the other two SNPs, rs17655 and rs873601, did not show any association (P > 0.001). Survival analysis revealed that rs751402 and rs2094258 had longer overall survival periods (P <0.001) than rs17655 and rs873601. Moreover, rs751402 and rs2094258 also had significantly longer overall survival (log-rank test, P < 0.005) for all three survival functions (positive family history, ER+PR status, and use of contraceptives), while rs17655 and rs873601 did not show any significant association. Only rs873601 showed a strong negative correlation with all the chemotherapeutic groups. Conclusion: The current results suggest that variations in ERCC5 may contribute to BC development and that their genetic anomalies may be associated with cancer risk and may be used as a biomarker of clinical outcome.

Correlation of MSH2 exonic deletions and protein downregulation with breast cancer biomarkers and outcome in Pakistani women/patients.

Mismatch repair (MMR) pathway is one of the underlying mechanisms of predisposition to breast cancer (BC). The present study explored the association of MSH2 exonic deletions, respective survival analysis, protein structure prediction, transcription profiling, and expression analysis with BC risk. Genotyping analysis of 493 BC cases and 387 controls confirmed the association of two MSH2 exonic deletions, i.e., exon 3 (OR:6.4, CI = 3.4-12.1) and 9 (OR:7.8, CI = 4.1-14.8) with BC risk. In order to confirm the phenotypic-genotypic relationship, we have performed MSH2 transcriptomic (p < 0.05) and protein expression analysis (OR:30, CI = 4-230) which further confirmed its downregulation/loss in BC biopsy samples highlighting potential role in the onset of breast carcinogenesis. Additionally, we have presented that MSH2 mutations can alter the expression profile of other BC associated biomarkers like ER, PR, CK-7, GATA-3, and E-cadherin. Subsequently, the effect of exonic deletions on secondary structure of protein has shown missing of beta and alpha helices in their protein products via in-silico analysis. However, loss of exon 3 results in the altered core protein structure leading to dysfunction protein, possible cause of BC development. No association of MSH2 exonic deletions with survival statistics was observed conceivably due to the shorter follow-up time. Thus, our results at genetic, transcriptomic, and proteomic levels confirmed the downregulated MSH2, emphasizing its potential contribution in MMR mechanisms for breast tumorigenesis. In conclusion, MSH2 deficiency may cause breast cancer development and progression.

Unraveling the Epidemiology, Geographical Distribution, and Genomic Evolution of Potentially Lethal Coronaviruses (SARS, MERS, and SARS CoV-2).

SARS CoV appeared in 2003 in China, transmitted from bats to humans via eating infected animals. It affected 8,096 humans with a death rate of 11% affecting 21 countries. The receptor binding domain (RBD) in S protein of this virus gets attached with the ACE2 receptors present on human cells. MERS CoV was first reported in 2012 in Middle East, originated from bat and transmitted to humans through camels. MERS CoV has a fatality rate of 35% and last case reported was in 2017 making a total of 1,879 cases worldwide. DPP4 expressed on human cells is the main attaching site for RBD in S protein of MERS CoV. Folding of RBD plays a crucial role in its pathogenesis. Virus causing COVID-19 was named as SARS CoV-2 due its homology with SARS CoV that emerged in 2003. It has become a pandemic affecting nearly 200 countries in just 3 months' time with a death rate of 2-3% currently. The new virus is fast spreading, but it utilizes the same RBD and ACE2 receptors along with furin present in human cells. The lessons learned from the SARS and MERS epidemics are the best social weapons to face and fight against this novel global threat.

XPC as breast cancer susceptibility gene: evidence from genetic profiling, statistical inferences and protein structural analysis.

BACKGROUND: Gene polymorphisms that affect nucleotide excision repair (NER) pathway may link with higher susceptibility of breast cancer (BC); however, the significance of these associations may vary conferring to the individual ethnicity. Xeroderma pigmentosum complementation gene (XPC) plays a substantial role in recognizing damaged DNA during NER process. OBJECTIVE AND METHODS: To estimate the relationship among XPC polymorphisms and breast cancer (BC) risk, we carried out a case-control-association study with 493 BC cases and 387 controls using TETRA-ARMS-PCR. Distributional differences of clinical features, demographic factors and XPC polymorphisms among BC cases and controls were examined by conditional logistic regression model. Kaplan-Meier test was applied to predict survival distributions and protein structure was predicted using computational tools. RESULTS: Obesity, consanguinity, positive marital status and BC family history were associated (P ≤ 0.01) with higher BC risk. Genotyping revealed significant involvement (P ≤ 0.01) of two XPC polymorphisms rs2228001-A > C (OR = 3.8; CI 1.9-7.6) and rs2733532-C > T (OR = 2.6; CI 1.4-5.03) in BC development, asserting them potential risk factors for increased BC incidence. However, no association (P > 0.05) was detected for overall or progression free survival for both XPC polymorphisms possibly due to shorter follow-up time (45 months). As compared to normal XPC structure, pronounced conformational changes have been observed in the C-terminus of XPCQ939K, bearing rs2228001-A > C substitution. In XPCQ939K, two additional α-helices were observed at A292-E297 and Y252-R286, while L623-M630 and L649-L653 helices were converted into loop conformation. CONCLUSION: In conclusion, both XPC polymorphisms confer significant association with increased BC risk. rs2228001 substitution may change the structural and functional preferences of XPC C-terminus, while rs2733532 may have regulatory role thereby leading to potential BC risk.

Correlation of MLH1 polymorphisms, survival statistics, in silico assessment and gene downregulation with clinical outcomes among breast cancer cases.

This study aimed to investigate the role of MLH1 polymorphisms, respective protein structure prediction, survival analysis, related clinicopathological details and MLH1 expression in breast cancer (BC). Genotyping of selected SNPs in BC patients (493) and age matched controls (387) were performed by Tetra-ARMS PCR. Gene expression among breast tumors (127) and adjacent control tissues were analysed using reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Statistical analysis was performed by SPSS and MedCalc. Conditional logistic regression analysis was applied to compute the odds ratio and confidence interval. Phyre2 and I-TASSER were used to generate MLH1 protein structures and verified by a variety of computational tools. Genotyping illustrated that MLH1 polymorphisms (rs63749795 and rs63749820) were significantly associated (P ≤ 0.05) with risk of developing BC. Down regulation of MLH1 gene expression/loss of the MLH1 protein (OR 12; CI 2.8-53.1) was observed in BC cases, illustrating its potential role in disease development. Moreover, loss of the MLH1 protein was found to be associated with higher grade cancer (P = 0.02) and lymph node positivity (P = 0.03), highlighting its essential role, as a component of the mismatch repair (MMR) machinery. Bioinformatics analysis confirmed that nonsense mutations produce a truncated MLH1 protein, causing a reduction in MMR efficiency. No association between MLH1 polymorphisms and overall and progression free survival statistics was observed among BC cases, possibly due to short follow-up study. Results at DNA, RNA and protein levels, along with in silico analysis, highlights the potential role of MLH1 in DNA repair mechanisms, within BC. Therefore, it was concluded that MLH1 may contribute towards BC development and progression.

Genetic polymorphism in ERCC5 and breast cancer risk.

ERCC5 plays crucial role in excision repair DNA damage induced by UV in NER pathway. Single neuleotide polymorphism in ERCC5 were responsible for different cancers. Therefore, current study evaluated the relationship between ERCC5 (rs1047768 T>C) polymorphism and the risk of breast cancer in Pakistani population. The rs1047768 polymorphism was screened among 175 females including one hundred breast cancer cases and age matched seventy-five healthy controls. Genotyping was performed with Tetra amplification-refractory mutation system (ARMS) PCR and products were observed through electrophoresis. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (95% CI) investigating relationship between genotypes, clinical parameters and risk of breast cancer. Statistical analysis exhibited significant relationship between the TC genotype (OR=7.2, 95% CI=1.5-34.3) and increased breast cancer risk. Moreover, family history (OR=6.25; 95% CI= 2.61-15.00) and late menopause (OR=2.41; 95% CI=1.20-4.83) were found to be breast cancer associated risk factors. In conclusion, ERCC5 (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer in Pakistani population.

Status of serine tyrosine kinase at germline and expressional levels in asthma patients.

Asthma is a disease marked by inflammation of airways with an increasing incidence rate worldwide especially among Asian population. Spleen tyrosine kinase (Syk) is known to be involved in regulation of such inflammation response and thereby rendering its inevitable importance among asthma patients. DNA extraction followed by PCR and sequencing was performed for genomic analysis, mRNA analysis was done by RT PCR whereas Western blot and ELISA was used for protein study. Image J and UNAFOLD were also used for Bioinformatics analysis.The mean age of patients and controls were 31.1±9.3 and 30.4±6.1 years respectively. Results of sequencing showed nonsense exonic mutations in exon 3 at g.25710G>A and g.25722G>A positions. Substitution mutations in introns were also found at g.25827G>A (intron 3), g.63425C>T (intron 8) and g.63445T>G (intron 8). Significantly increased levels of IgE and significantly decreased expression of Syk at transcriptional level was found in patients compared to controls. The western blot results of asthmatic samples and healthy controls revealed that Syk has comparatively low expression in diseased individual's PBMCs. SYK has been found to be altered in DNA, mRNA and protein expression in asthma patients among Pakistani population therefore patients should be treated according to their Syk status for more effective recovery.

Hypertension associated risk factors in Pakistan: A multifactorial case-control study.

OBJECTIVE: To shed light on the association of age, smoking, educational status, family history, diabetes and kidney diseases with hypertension. METHODS: The case-control study was conducted at three different medical centres of Rawalpindi, Pakistan, from December 2016 to July 2017. Data from 549 hypertensive cases and 1451 normotensive controls was collected using a detailed questionnaire and through personal interviews by adopting nonprobability consecutive sampling technique. Overall 2000 adult individuals, both males and females excluding pregnant women, were the part of this study. Those with blood pressure ≥140/90mmHg and taking anti-hypertensive treatment were designated as the cases, while the rest were taken as normotensive controls. Blood pressure was measured by a physician. Multivariate logistics regression analysis was used to estimate the association of various different risk factors with hypertension. All the analysis was performed using software R 3.4.2 and SPSS 24. RESULTS: Of the 2,000 subjects, 549(27.45%) were hypertensive cases and 1451(72.55%) were normotensive controls. Mean age of the cases was 43.32}9.7 years and it was 31.8}10.1 years among the normotensives. Higher age, smoking, lower educational status, presence of kidney diseases, diabetes and family history of hypertension were significantly associated with hypertension (p<0.01 each). CONCLUSIONS: In Pakistani population, age, smoking, illiteracy, kidney diseases, diabetes and family history were found to be associated with hypertension.

Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.

OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups. METHODS: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24. RESULTS: There were 347 subjects with a mean age of 44.3±12.2 years and body mass index of 27.9±4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options. CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.

Silver nanoparticle impregnated chitosan-PEG hydrogel enhances wound healing in diabetes induced rabbits.

Non-healing wounds are among the serious complications of type-2-diabetes around the globe, associated with high incidence of bacterial infection, chronic nerve and blood vessel damage, and eventually repeated amputation of limbs and organs. Silver nanoparticles offer strong wound healing potential due to their well-known antibacterial activities. The present study reports the development of silver nanoparticle impregnated chitosan-poly ethylene glycol (PEG) hydrogel to accelerate wound healing in diabetic patients. The aim of the study was to formulate a sustained and slow release of silver nanoparticle using chitosan-PEG-Silver Nitrate based hydrogel for the treatment of chronic diabetic wounds. The silver nanoparticle containing chitosan-PEG pre-polymer solution was synthesized by reducing silver nitrate with PEG and chitosan solution, thereby, transforming the silver ions into silver nanoparticles. The resulted pre-polymer solution was then crosslinked using glutaraldehyde to form the desired hydrogel. The developed silver nanoparticle impregnated chitosan hydrogel was characterized using ultra-violet (UV) visible spectrophotometry, Fourier Transform-infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) followed by the determination of porosity, and swelling properties. The release of AgNPs from hydrogel was determined by UV-vis spectroscopy followed by antimicrobial and antioxidant assays. The wound healing efficacy of the synthesized hydrogel was evaluated in diabetic rabbits. The results demonstrated a higher porosity, higher degree of swelling and higher water vapor transition rate (WVTR) for silver nanoparticle impregnated hydrogel compared to bare chitosan-PEG hydrogel as well as improved antimicrobial and antioxidant properties in-vitro and enhanced wound healing capability in-vivo in diabetic rabbits. The hydrogel showed a slow and sustained release of AgNPs over a period of at least seven days manifesting the slow biodegradation of developed hydrogels. The improved antimicrobial, antioxidant and wound healing results indicate that the silver nanoparticle impregnated chitosan-PEG hydrogel can be a promising material for wound healing dressing for chronic diabetic wounds.

Expressional analysis of MLH1 and MSH2 in breast cancer.

BACKGROUND: Mismatch repair proteins are ubiquitous keys in diverse cellular functions and protects the genome by correcting mismatch as post replication error correction machinery. Mismatch repair deficiency was associated with tumor development and progression therefore, current study was aimed to investigate MLH1 and MSH2 expression in breast cancer and correlate patients' clinicopathological factors with status of mismatch repair genes. MATERIAL AND METHODS: Breast cancer tissues with adjacent normal tissue along with clinical details were collected during surgery from 80 cases. Immunohistochemistry was performed with primary and secondary antibodies for expressional analysis. Results were analyzed using SPSS version 24. RESULTS: Immunohistochemical analysis revealed that both MLH1 and MSH2 were crucial in maintaining DNA repair system and loss of these 2 mismatch repair proteins may lead to adverse outcomes in breast cancer. Statistically significant association was found between loss of MLH1 (P = 0.0004; odds ratio 13.8; 95% confidence interval 4.6-41.1), MSH2 (P = 0.0002; odds ratio 14.0; 95% confidence interval 4.7-42.2) and breast cancer. Statistical analysis demonstrated that MLH1 and MSH2 deficiency may lead breast cancer progression to advanced stage, correlated with tumor focality (MLH1 P = 0.001; MSH2 P = 0.002) and chemotherapy (MLH1 P = 0.01; MSH2 P = 0.04). Presence of CK7, GATA 3, and E cadherin tends to increase in mismatch repair deficient breast cancer. Whereas, no association of mismatch repair deficiency was observed with age, tumor grade, positive lymph nodes, menopause, and ER and/or PR status. CONCLUSION: Loss of mismatch repair proteins in breast cancer highlights its potential role in DNA repair mechanisms and helps tumor cells to become resistant against chemotherapeutic drugs. Therefore, mismatch repair deficiency may contribute to breast cancer progression.

Evaluation of the rs3088442 G>A SLC22A3 Gene Polymorphism and the Role of microRNA 147 in Groups of Adult Pakistani Populations With Type 2 Diabetes in Response to Metformin.

OBJECTIVES: Type 2 diabetes is a complex genetic disorder, and a large number of genetic polymorphisms may be involved in its pathogenesis. Pharmacologically, type 2 diabetes can be treated with 9 different approved classes of drugs, but metformin is suggested as the first line of therapy, followed by sulfonylureas. METHODS: This was a case-control study consisting of 300 metformin responders and 300 metformin nonresponders in patients with type 2 diabetes and 300 healthy Pakistani subjects. Genotyping of the SLC22A3 G>A polymorphism was performed by allele-specific polymerase chain reaction (PCR) for microRNA 147 expression; real-time polymerase chain reaction was used, and expressional analysis of SLC22A3 was done by semiquantitative polymerase chain reaction. RESULTS: GA and AA genotypes were highly significantly associated with the drug treatments when compared with controls. A statistically significant difference was observed in the distribution of the SLC22A3 A allele between healthy subjects and patients with type 2 diabetes. When odds ratios were adjusted for glycated hemoglobin levels and postprandial and fasting blood glucose levels, our findings showed that the overexpression of allele A of the rs3088442 G>A variant may act as a protective allele and is associated with the clinical response to metformin. microRNA 147 expression was found to be increased in patients who were metformin responders compared with the nonresponder group and controls. mRNA expression of SLC22A3 was significantly reduced in patients taking metformin as compared to other groups. CONCLUSIONS: These results suggested that the SLC22A3 rs3088442 at position 2282 A allele may confer metformin clinical responses in patients with type 2 diabetes in the Pakistani population. Overexpression of microRNA 147 is associated with a downward expression of the SLC22A3 gene in patients who have type 2 diabetes.

Cancer Immunomics in the Age of Information: Role in Diagnostics and Beyond.

Cancer genome sequencing is useful for diagnosis and personalized treatment. Analysis of the sequencing data involves integration of computation, statistics and system biology methods. The amalgam of such methods which help study interaction of cancer cells with immune system, harnessing immune system for cancer therapy or its prevention through vaccines has led to the foundation of cancer immunomics. It is, therefore, a combinatorial science which merges diverse techniques from genomics and proteomics for diagnosis and drug design/treatment. There has been a gradual increase in establishment of cancer immune focused start-ups, research facilities and pharma giants working on state-of-the-art methods for improving diagnostics, treatment and prevention or minimizing side effects, applying immunomics. However, we are still far away from making precise, quick and reliable diagnostic and treatment predictions. We need decision support systems to facilitate diagnosis, tumor evaluation prediction and assessment of individual profile for making personalized therapy a reality. The future is centered not only on data management but wise decision aided by artificially intelligent algorithms. In this review, we provide an overall picture and focus on immune biomarkers and relevant softwares that aid in diagnostics and analysis of cancer.

An insight into clinical outcome of XPG polymorphisms in breast cancer.

XPG polymorphisms are associated with varied clinical outcomes in different cancers but up-till now no study has been reported on breast cancer. Therefore, current study was aimed to explore the association of breast cancer risk factors and XPG polymorphisms (rs2296147 and rs1047768). It also investigated impact of XPG variants on overall survival and progression free survival among breast cancer cases. A total of 493 histopathologically identified breast cancer cases and 387 healthy females were genotyped by ARMS-PCR. Relationship between general characteristics, XPG polymorphisms and breast cancer risk was accessed by conditional logistic regression and illustrated by OR and 95% CI. Kaplan Meier test was applied to estimate survival distributions whereas log rank test demonstrated survival differences. Association of XPG variants with OS and PFS in breast cancer was illustrated by HR and 95% CI. Early onset of menopause, consanguinity and family history contributed (P < 0.05) towards breast cancer development. Both rs2296147 and rs1047768 SNPs were found to be associated (P < 0.05) with the risk of breast cancer. XPG rs1047768 was significantly associated with decreased PFS (HR 1.72; 95% CI 1.0-2.8) in breast cancer cases (P = 0.013) which was demonstrated by median time of 26 months for T > C variant when compared with median time of 37 months for TT genotype. No association was found between XPG rs2296147 polymorphism and survival analysis among breast cancer cases. XPG (rs1047768 T > C) variant may play a significant role in terms of decreased PFS and could be used as a predictor of unfavourable prognosis among breast cancer.

Risk factors for prostate cancer: A multifactorial case-control study.

Prostate cancer is the third most commonly diagnosed cancer among Pakistani men. It is a multifactorial disease involving genetics together with environmental factors. Countries where men have greater dietary fat intake showed increased prostate cancer mortality rates. A population based case-control study was conducted to evaluate various prostate cancer risk factors. Study subjects were 896 prostate cancer cases (2010-2015) and 900 age matched controls. Odds ratio (OR) and 95% CI were used to estimate the association between different risk factors and prostate cancer. P values for different factors were computed by t-test, chi-square test, and Fisher exact test. Results showed significant association of increased age (OR = 10.6; CI: 7.92-14.31; P = 0.0001; Z = 15.7) and smoking (P = 0.05) with risk of disease. Consistent evidence suggested that fruits (P = 0.0001), vegetables (P = 0.0007), and diabetes mellitus (OR = 0.84; CI: 0.72-0.97; P = 0.02; Z = 2.28) were significantly associated with decreased prostate cancer risk. Comparison of education, marital status, occupation, intake of meat (<100 grams/week, 101-250 grams/week, >250 grams/week), number of cigarettes smoked per day, smoking duration, and family history of disease among cases and controls were not associated (P > 0.05) with risk of prostate cancer. Most of the prostate cancer patients were at stage IV with a Gleason score ranging from 7-9 and had undergone surgery. This epidemiological study illustrated that age and smoking were potential risk factors for prostate cancer in Pakistani men. Furthermore, phytonutrients can reduce its risk to a greater extent. Prospective studies with detailed analysis and greater sample size are required to explore more accurate findings.