Interactive Association of XRCC1, XRCC2, XRCC3, and TP53 Gene Polymorphisms With Gastrointestinal Cancer Risk: Insights From a Hospital-Based Case-Control Study.

BACKGROUND AND AIM: Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1, XRCC2, XRCC3, and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility. MATERIALS AND METHODS: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05). RESULTS: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population. CONCLUSIONS: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.

Single-nucleotide polymorphism in CYP1A1, CYP1B1, CYP2B6, CYP2C8, and CYP2C9 genes and their association with gastrointestinal cancer: A hospital-based case-control study.

BACKGROUND: Cytochrome P450 (CYP) comprises a group of phase-I metabolizing enzymes that are important in xenobiotics metabolism. Genetic polymorphism of CYPs has been comprehensively studied for their association with a range of diseases. In this study, we assessed single-nucleotide polymorphism (SNP) of CYP1A, CYP1B, CYP2B, and CYP2C and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra. MATERIALS AND METHODS: In this hospital-based case-control study, the association of polymorphism of CYP genes was studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study subjects included 200 clinically confirmed GI cancer patients and equal number of healthy controls. Odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to find out the level of association, where P ≤ 0.005 was considered statistically significant. RESULTS: After the analysis of CYP1A1*2A (rs4646903), CYP1B1*3 (rs1059836), CYP2B6*5 (rs3211371), CYP2C8*2 (rs11572103), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), we noticed that variant (T) allele of CYP2B6*5 possessed significantly elevated risk (OR = 4.43; 95% CI: 2.20-8.90; P < 0.0001) of GI cancer in studied population. The genotypic distribution of G/C heterozygote allele of CYP1B1*3 (OR = 0.19, 95% CI = 0.12-0.32; P < 0.0001) and homozygous variant C/C allele (OR = 0.24, 95% CI = 0.13-0.45; P < 0.0001) showed a negative association with the development of GI cancer. CONCLUSION: The findings from this study supported that polymorphism of CYP2B6*5gene may be involved in the development of GI cancer. However, other SNPs of CYP1A, CYP1B, and CYP2C genes did not signify the risk for GI cancer in the studied population of rural Maharashtra.

Endometriosis Resection Using Nerve Sparing Versus Non-nerve Sparing Surgical Techniques.

Introduction: Endometriosis is the condition in which there are ectopic endometrial tissues outside the uterine cavity. The use of nerve sparing technique has been well established in the field of oncology, leading to better quality of life following radical oncologic procedures without compromising on the long-term survival. The objective of this study is to compare the quality of life in terms of sexual function and urinary function in women undergoing nerve sparing surgeries for endometriosis and those undergoing non-nerve sparing surgeries. Material and Methods: Data of 51 patients operated for endometriosis at Galaxy Care Laparoscopic Institute, Pune, India between 1st January 2020 till 31st December 2020 were collected and analysed. We included patients in age group between 38 and 44 years in monogamous relationship, with moderate to severe endometriosis (Revised American Society of Reproductive Medicine r-ASRM score of 16 and above 5), being operated for hysterectomy along with ureterolysis and/or bowel resection (including shaving of rectal endometriosis, discoid resection, segmental resection), and excision of large ovarian endometriomas (> 3 cm size) with cul-de-sac obliteration. Results: The patients were evaluated for the following factors: age, parity, nature of surgery done, immediate intraoperative complications (bowel injury, bladder injury, ureteric injury), operative time in minutes, average blood loss, length of hospital stay, days to removal of foley's catheter and postoperative urinary and sexual function which were assessed on follow up visit and a 1-year follow up interview. We found that the urinary and sexual function in the group undergoing nerve sparing surgeries was significantly better than the patients undergoing non-nerve sparing surgeries. Conclusion: Laparoscopic nerve sparing approach for clearance of endometriosis has allowed better quality of life post surgery. Proper understanding and demonstration of pelvic neuroanatomy has made this approach feasible and achievable in carefully selected patients.

Genetic polymorphisms of CYP1A, CYP1B, CYP2C and risk of cervical cancer among rural population of Maharashtra: Findings from a hospital-based case-control study.

BACKGROUND: Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra. MATERIALS AND METHODS: In this case-control study, genetic association of the polymorphisms in CYP genes was studied by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 350 clinically confirmed CC patients and 350 healthy volunteers in a population of south-western Maharashtra. The odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to get the level of association where P ≤ 0.005 was considered as statistically significant. RESULTS: After the analysis of single-nucleotide polymorphism (SNPs) of CYP1A1, CYP1B1, CYP2C8, CYP2C9, and CYP2C19, we noticed that CYP1B1*3 rs1056836 (Leu4326Val) polymorphism possessed a significantly elevated risk (OR = 3.28; 95% CI: 2.18-4.94; P < 0.0001), whereas CYP2C19*2 rs4244285 showed significantly lower risk (OR: 0.53, 95% CI: 0.33-0.85 P < 0.009) of CC in the studied rural population. CONCLUSION: The findings from this study supported that rs1056836 SNP of CYP1B1*3 increase CC development, whereas rs4244285 of CYP2C19*2 lowers the CC risk in the studied population.

Impact of Polymorphism in Base Excision Repair and Nucleotide Excision Repair Genes and Risk of Cervical Cancer: A Case-Control Study.

BACKGROUND: Last few years, several studies all over the world revealed the association of DNA repair genes with risk of developing different type of cancers, but were ambiguous to support the evidences in case of cervical cancer risk. These differences in earlier studies directed us to study the association of polymorphisms of BER genes (XRCC1, hOGG1, XPC) and NER genes (XPC, XPD) with cervical cancer susceptibility in the women of rural population of Maharashtra. MATERIALS AND METHODS: The genetic polymorphism in BER and NER pathway genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using DNA isolated from intravenous blood samples of patients and normal controls. The study included 400 clinically confirmed cervical cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The association of polymorphisms was confirmed by Odds ratio (OR) with 95% confidence interval. RESULTS: The single nucleotide polymorphism (SNP) of BER genes including XRCC1, hOGG1 and APE1 were analyzed and the results were noted that 27466AA (OR=4.88; 95% CI: 3.61- 6.60; p<0.0001) and 28152AA (OR=2.89; 95% CI: 1.57- 5.31; p=0.0005) genotypes of XRCC1 (rs25489, rs25487) were significantly associated with cervical cancer risk. The 1245GG genotype of hOGG1 (rs1052133) (OR=45.30; 95% CI: 3.76- 7.46; p=0.001) also showed significant correlation, whereas 2197GG genotype of APE1 (rs1130409) gene showed negative association with cervical carcinogenesis (OR=0.59; 95% CI: 0.35- 0.97; p=0.005). Similarly when we studied SNPs of NER genes including XPC and XPD genes, 21151TT genotype of XPC (rs 2228000) was positively associated with cervical cancer development and 23591AA genotype of XPD (rs1799793) showed negative association (OR=0.34; 95% CI: 0.17- 0.64; p=0.001). CONCLUSION: The findings from this study supported that rs25489, rs25487SNPs of XRCC1, rs1052133 of hOGG1 and rs2228000 of XPC may increase cervical cancer risk, whereas rs1130409 SNP of APE1 and rs1799793 SNP of XPD gene lower the risk of cervical cancer in the studied population.

Biogenic synthesis of gold nanoparticles using Argemone mexicana L. and their cytotoxic and genotoxic effects on human colon cancer cell line (HCT-15).

BACKGROUND: Nanomedicine has evolved as precision medicine in novel therapeutic approach of cancer management. The present study investigated the efficacy of biogenic gold nanoparticles synthesized using Argemone mexicana L. aqueous extract (AM-AuNPs) against the human colon cancer cell line, HCT-15. RESULTS: Biosynthesis of AM-AuNPs was determined by ultraviolet-visible spectroscopy and further characterized by transmission electron microscopy, X-ray diffraction, and Fourier transition infrared spectroscopy analysis. The cytotoxic activity of AM-AuNPs was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas genotoxicity was evaluated by the DNA fragmentation assay. The expression of apoptosis regulatory genes such as p53 and caspase-3 was explored through semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting to evidence apoptotic cell death in HCT-15 cells. Biogenic AM-AuNPs inhibited cell proliferation in HCT-15 cell line with a half maximal inhibitory concentration (IC50) of 20.53 µg/mL at 24 h and 12.03 µg/mL at 48 h of exposure. The altered cell morphology and increased apoptosis due to AM-AuNPs were also evidenced through nuclear DNA fragmentation and upregulated expression of p53 and caspase-3 in HCT-15 cells. CONCLUSION: The AM-AuNPs may exert antiproliferative and genotoxic effects on HCT-15 cells by cell growth suppression and induction of apoptosis mediated by activation of p53 and caspase-3 genes.

Practical approach to the pathologic diagnosis of gastritis.

CONTEXT: Most types of gastritis can be diagnosed on hematoxylin-eosin stains. The most common type of chronic gastritis is Helicobacter pylori gastritis. Reactive or chemical gastropathy, which is often associated with nonsteroidal anti-inflammatory drug use or bile reflux, is common in most practices. The diagnosis of atrophic gastritis can be challenging if few biopsy samples are available and if the location of the biopsies in the stomach is not known, such as when random biopsies are sampled in one jar. If the biopsy site is not known, immunohistochemical stains, such as a combination of synaptophysin and gastrin, are useful in establishing the biopsy location. OBJECTIVE: To demonstrate a practical approach to achieving a pathologic diagnosis of gastritis by evaluating a limited number of features in mucosal biopsies. DATA SOURCE: In this article, we present several representative gastric biopsy cases from a gastrointestinal pathology practice to demonstrate the practical application of basic histopathologic methods for the diagnosis of gastritis. CONCLUSIONS: Limited ancillary tests are usually required for a diagnosis of gastritis. In some cases, special stains, such as acid-fast stains, and immunohistochemical stains, such as for H pylori and viruses, can be useful. Helicobacter pylori immunohistochemical stains can particularly contribute (1) when moderate to severe, chronic gastritis or active gastritis is present but no Helicobacter organisms are identified upon hematoxylin-eosin stain; (2) when extensive intestinal metaplasia is present; and (3) in follow-up biopsies, after antibiotic treatment for H pylori.