Methyl jasmonate inducible UGT79A18 is a novel glycosyltransferase involved in the bacoside biosynthetic pathway in Bacopa monnieri.

Bacosides are dammarane-type triterpenoidal saponins in Bacopa monnieri and have various pharmacological applications. All the bacosides are diversified from two isomers, i.e., jujubogenin and pseudojujubogenin. The biosynthetic pathway of bacoside is not well elucidated. In the present study, we characterized a UDP-glycosyltransferase, UGT79A18, involved in the glycosylation of pseudojujubogenin. UGT79A18 shows higher expression in response to 5 h of wounding, and 3 h of MeJA treatment. The recombinant UGT79A18 shows in vitro activity against a wide range of flavonoids and triterpenes and has a substrate preference for protopanaxadiol, a dammarane-type triterpene. Secondary metabolite analysis of overexpression and knockdown lines of UGT79A18 in B. monnieri identify bacopasaponin D, bacopaside II, bacopaside N2 and pseudojujubogenin glucosyl rhamnoside as the major bacosides that were differentially accumulated. In the overexpression lines of UGT79A18, we found 1.7-fold enhanced bacopaside II, 8-fold enhanced bacopasaponin D, 3-fold enhanced pseudojujubogenin glucosyl rhamnoside, and 1.6-fold enhanced bacopaside N2 content in comparison with vector control plant, whereas in the knockdown lines of UGT79A18, we found 1.4-fold reduction in bacopaside II content, 3-fold reduction in the bacopasaponin D content, 2-fold reduction in the pseudojujubogenin glucosyl rhamnoside content, and 1.5-fold reduction in bacopaside N2 content in comparison with vector control. These results suggest that UGT79A18 is a significant UDP glycosyltransferase involved in glycosylating pseudojujubogenin and enhancing the pseudojujubogenin-derived bacosides.

Prevalence of Menstrual Disorder in Women and Its Correlation to Body Mass Index and Physical Activity.

Background: Regular menstruation represents reproductive health and quality of life of women. However, many women suffer from menstrual disorders at some point in their life. The occurrence of such abnormalities is affected by two key factors: BMI and physical activity. This study aims to analyse the relationship of these two factors to menstrual disorders. Materials and Method: A cross-sectional study was conducted among 502 women in Uttar Pradesh, India, from July 2021 to January 2023. Samples were selected using purposive sampling technique. The data were analysed using Pearson's Chi-square test on MS Excel 2013 and IBM SPSS 29.0.0.0 (240) software. Results: Mean age of the research subjects was 25.84 + 6.30 years, mean weight was 60.29 + 11.22 kg, mean height was 155.34 + 11.77 cm, and mean BMI was 25.36 + 6.06 kg. 68.92% subjects had regular age at menarche. Most common menstrual disorders were PMS (41.63%) and dysmenorrhea (28.29%). As per BMI categories, most disorders were found in obese (94.87%) and underweight (93.62%) subjects. As per physical activity categories, most disorders were found in low (76.55%) and high (76.40%) category subjects. A significant relationship was found between menstrual disorder and BMI (χ2 = 80.49, p < 0.001) and physical activity (χ2 = 70.09, p < 0.001). Conclusion: The menstrual disorders in women are significantly related to their BMI and physical activity. Women are advised to focus on having a balanced, nutritious diet and indulge in moderate physical activity to improve their reproductive health and quality of life.

Copy number variations in male breast cancer.

Common copy number variations often contain cancer-related genes and are likely to play a role in carcinogenesis. Different mechanisms of tumorigenesis are suggested in female and male breast cancer because of different molecular profiles. The cytogenetic analysis of GTG-banded chromosomes was performed in six male patients with infiltrating ductal carcinoma and six healthy male controls matched for age. Single-nucleotide polymorphism (SNP) array analysis was performed in male breast cancer (MBC) patients. Cytogenetic analysis found aberrations previously implicated in cancer. SNP array analysis in patients revealed a gain of Xp11.23, 8p23.2, Yq11.221, Yq11.3 (AZF region), 12p11.21, 18q12.1, and 17q21.3; a loss of Yq11.222 and 7q11.21; and a loss of heterozygosity of 4p16.3, 6p12.3, 6p22.2-p21.31, 7p14.2-14.1, 18q11.2-q12.1, 20p11.23-11.1, 20q11.21-11.23, 1q25.2-q25.3, 2q11.1-q11.2, 5q23.1-23.2, 11p15.4-15.3, and 22q13.1-13.31. Some of these variations, especially those of the Y-chromosome, have not been reported earlier. Chromosomal loci identified by SNP array harbor genes were reported to be associated with cancer progression and metastasis, indicating their involvement in MBC also.

RAD51 135G>C polymorphism in esophageal cancer and meta-analysis in gastrointestinal tract cancers.

Background: A functional single-nucleotide polymorphism (SNP), 135G>C in the 5'UTR of the RAD51 gene, affects gene transcription activity with implications for the repair of damaged DNA related to tumorigenesis. Previous limited reported genetic studies to link the 135G>C polymorphism of RAD51 gene to the risk of gastrointestinal tract (GIT) cancers, especially esophageal cancer (EC), have been inconclusive. Materials and Methods: The polymorphism was evaluated by RFLP-PCR in 252 EC patients and 252 healthy controls from Amritsar, Punjab, India, for case-control study. For a meta-analysis, a total of 78 studies on GIT cancers were assessed, out of which 14 eligible studies (including the present study) comprising 2842 cases and 3224 controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) and Chi-square test were used to assess the association in different inheritance models. Results: The GC genotype (OR: 0.45, 95% CI: 0.29-0.68) and C allele (OR: 0.52, 95% CI: 0.36-0.75) were significantly lower (P = 0.0005) in cases as compared to controls. There was no significant association with any genetic model in the meta-analysis. Conclusion: C allele provides protection for EC in the studied population contrary to previous reports in Polish, Chinese population probably due to ethic differences. Compared with previous meta-analysis on individual GIT cancers, present meta-analysis included all GIT cancers but found no association.

Association of MTHFR 677C>T polymorphism with breast cancer risk: A case-control study and meta-analysis.

Background and Objectives: Breast cancer is a complex, multifactorial disease that arises as a result of interactions between multiple genes and environmental factors. Methylenetetrahydrofolate reductase (MTHFR) is a low susceptibility gene, involved in folate metabolism. It assists in conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate which further leads to DNA methylation. 5,10-methylenetetrahydrofolate assists in conversion of uracil to thymine and purine synthesis for DNA synthesis. MTHFR 677C>T polymorphism alters the activity of MTHFR enzyme potentially effecting DNA repair and synthesis, hence a potential risk for cancer like breast cancer. Hence, the present study was conducted to evaluate association of MTHFR 677C>T polymorphism and breast cancer in Punjabi population. Moreover, a meta-analysis was conducted to address the same. Materials and Methods: A total of 247 breast cancer patients and 247 controls were selected from Punjabi population for analysis using PCR-RFLP method. For meta-analysis, 67 studies were selected, and allele contrast, homozygous, heterozygous, dominant, and recessive models were used to evaluate the association between MTHFR 677C>T and breast cancer. Results: The frequencies of CC, CT, and TT genotype were 68.4% versus 74.5%, 28.7% versus 23.5%, and 2.9% versus 2.0% in patients and controls, respectively. There was no significant difference found. In meta-analysis, significant association was found in overall and Asian population while no significant association was found in Caucasians. Interpretation and Conclusions: MTHFR 677C>T polymorphism is not a risk factor for breast cancer in Punjabi population. Inconsistency with the meta-analysis can be due to ethnic diversity.

An insight into microRNA biogenesis and its regulatory role in plant secondary metabolism.

KEY MESSAGE: The present review highlights the regulatory roles of microRNAs in plant secondary metabolism and focuses on different bioengineering strategies to modulate secondary metabolite content in plants. MicroRNAs (miRNAs) are the class of small endogenous, essential, non-coding RNAs that riboregulate the gene expression involved in various biological processes in most eukaryotes. MiRNAs has emerged as important regulators in plants that function by silencing target genes through cleavage or translational inhibition. These miRNAs plays an important role in a wide range of plant biological and metabolic processes, including plant development and various environmental response controls. Several important plant secondary metabolites like alkaloids, terpenoids, and phenolics are well studied for their function in plant defense against different types of pests and herbivores. Due to the presence of a wide range of biological and pharmaceutical properties of plant secondary metabolites, it is important to study the regulation of their biosynthetic pathways. The contribution of miRNAs in regulating plant secondary metabolism is not well explored. Recent advancements in molecular techniques have improved our knowledge in understanding the molecular function of genes, proteins, enzymes, and small RNAs involved in different steps of secondary metabolic pathways. In the present review, we have discussed the recent progress made on miRNA biogenesis, its regulation, and highlighted the current research developed in the field of identification, analysis, and characterizations of various miRNAs that regulate plant secondary metabolism. We have also discussed how different bioengineering strategies such as artificial miRNA (amiRNA), endogenous target mimicry, and CRISPR/Cas9 could be utilized to enhance the secondary metabolite production in plants.

Association of VEGF haplotypes with breast cancer risk in North-West Indians.

BACKGROUND: Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. METHODS: Samples of 250 breast cancer patients and 250 age and sex matched controls were genotyped for VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. RESULTS: Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38-0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44-0.92; p = 0.018) of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10-3.56; p = 0.02). CONCLUSIONS: Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.

Knowledge about the COVID-19 pandemic among undergraduate medical and dental students in Lalitpur, Nepal.

Background: Coronavirus disease-19 (COVID-19) has become a major global problem. There is an urgent need to measure the knowledge of the disease among health science students who can play an active role in pandemic control. The research was conducted to examine COVID-19 knowledge among medical and dental students in a Nepalese medical college, compare the knowledge to other studies in the literature and identify educational needs of students who may be involved in treating COVID-19 patients. Methods: The cross-sectional study was performed during the third week of June among first to final year medical and dental students. As the country was in lockdown, a structured online questionnaire was used. The responses obtained were entered into IBM SPSS Statistics for Windows and the normality of the data checked using one-sample Kolmogorov Smirnov test. The demographic parameters were tabulated, and total score compared among different subgroups of participants. The frequency of different measures mentioned by respondents were also noted. Results: More than half of the participants were females (59.6%). Nearly half 282 (49.8%) belonged to age group 21-23 years. The majority 415 (73.5%) were undergraduate medical and 150 (26.5%) were undergraduate dental students. The largest number of respondents, 140 (24.9%), were from the second year of study and 344 (60.9%) were from urban areas. The median total score was 20 and the interquartile range 4. The maximum possible score was 29. The scores among students belonging to different years of study were significantly different (p=0.006). Total scores were not significantly different among other subgroups. Conclusions: The knowledge of the participants was good. Deficiencies in knowledge were noted in certain areas and these should be addressed through an educational intervention. One of the challenges is the rapid evolution of our knowledge about this condition, which may require regular refresher sessions. Similar studies can be undertaken in other medical colleges in the country and in nursing and pharmacy colleges.

In silico pathway analysis based on chromosomal instability in breast cancer patients.

BACKGROUND: Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. METHODS: Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 h Peripheral lymphocyte culturing and GTG-banding. Reactome database from Cytoscape software version 3.7.1 was used to perform in-silico analysis (functional interaction and gene enrichment). RESULTS: Frequency of chromosomal aberrations (structural and numerical) was found to be significantly higher in patients as compared to controls. The genes harbored by chromosomal regions showing increased aberration frequency in patients were further analyzed in-silico. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. CONCLUSION: The current study employs the information inferred from chromosomal instability analysis in a non-target tissue for determining the genes and the pathways associated with breast cancer. These results can be further extrapolated by performing either mutation analysis in the genes/pathways deduced or expression analysis which can pinpoint the relevant functional impact of chromosomal instability.

Screening of BRCA1 variants c.190T>C, 1307delT, g.5331G>A and c.2612C>T in breast cancer patients from North India.

The polymorphic variants of BRCA1, which lead to amino acid substitutions, have a known pathogenic role in breast cancer. The present study investigated in North Indian breast cancer patients the association of risk with four reported pathogenic variants of BRCA1: c.190T>C (p.Cys64Arg), 1307delT, g.5331G>A (p.G1738R) and c.2612C>T (p.Pro871Leu). Genotyping was done by PCR-RFLP method in 255 clinically confirmed breast cancer patients and 255 age and gender matched healthy individuals. For c.190T>C, 1307delT and g.5331G>A, all the patients and controls had the wild-type genotype indicating no association with breast cancer risk. For c.2612C>T polymorphism, the frequency of the CC, CT, and TT genotypes was 14.5 vs 15.7%, 59.6 vs 53.7% and 25.9 vs 30.6% in breast cancer patients and controls respectively. The frequency of heterozygotes (CT genotype) was higher in cases than controls but the difference was not statistically significant. Genetic model analysis showed no association of the four analyzed BRCA1 variants with breast cancer risk with any model. The studied variants were not associated with the risk of breast cancer in Punjab, North west India, suggesting a need for further screening of other BRCA1 variants. It is the first reported study on these 4 variants from India.

Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk.

AIM: The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high. METHODS: The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene-gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression. RESULTS: For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3-0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26-0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27-0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0-2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r 2=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk. CONCLUSION: XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.

Linkage disequilibrium and haplotypes of five TP53 polymorphisms in oesophageal cancer patients.

The aim of present study was to evaluate the linkage disequilibrium (LD) of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphism of TP53 and their haplotypes association with oesophageal cancer risk in patients from Punjab, northwest India. A total of 466 samples, including 233 oesophageal cancer patients and 233 healthy individuals were analysed. Data analysis revealed the gender specific association. In female group, arginine-proline (RP) genotype (P = 0.08) and P allele (P = 0.07) of p.R72P polymorphism was marginally associated with increased risk of oesophageal cancer. A1A2 genotype (P = 0.06) and A2 allele (P = 0.07) of PIN3 Ins16bp polymorphism was marginally associated with decreased risk of oesophageal cancer in male group. A1A2-GA genotype combination (P = 0.04) of PIN3 and r.13494g[a polymorphisms was significantly associated with decreased risk of oesophageal cancer in male group. In female group, PP-GA genotype combination (P = 0.02) of p.R72P and r.13494g[a polymorphisms and RP-A1A1-GG genotype combination (P = 0.04) of p.R72P, PIN3 and r.13494g[a polymorphisms was significantly associated with increased risk of oesophageal cancer. We observed moderate LD between two intronic polymorphisms PIN3 Ins16bp and r.13494g[a (D´ = 0.90; r2 = 0.68). Haplotype analysis revealed that none of the haplotype combination was associated with oesophageal cancer risk when both the genders were considered. Stratification on the basis of gender showed that P-A2-P-A-A haplotype of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphisms was marginally associated with reduced oesophageal cancer risk in male group (P = 0.08). Replication of these findings in independent cohorts may be insightful for the role of TP53 in oesophageal cancer pathogenesis.

Risk Factor Analysis for Breast Cancer in Premenopausal and Postmenopausal Women of Punjab, India.

OBJECTIVE: Amritsar, the second largest town of agrarian state of Punjab, India reports high number of breast cancer cases every year. The present study investigated the etiology of breast cancer using various obesity indices and other epidemiological factors among breast cancer patients residing in and around Amritsar city. METHODS: In this case control study, risk factors for breast cancer were analyzed in 542 female subjects: 271 females with breast cancer patients and 271 unrelated healthy females matched for age as control females. RESULTS: Bivariate analysis for risk factors in cases and controls showed a lower risk (OR=0.65, 95% CI 0.43-0.99, p=0.04) in obese cases with BMI≥25kg/m2 as compared to subjects with normal BMI. Risk factor analysis showed that parameter which provided risk for cancer in postmenopausal women was obesity and in premenopausal women was parity. Postmenopausal women with BMI (overweight: OR=0.39, 95% CI 0.17-0.92, p=0.03; obese: OR= 0.26, 95% CI 0.13-0.52, p=0.00), WC (OR=0.17, 95% CI 0.05-0.52, p=0.00) and WHtR (p=0.02) had highr risk. Premenopausal women with 3 or less than 3 children had a higher risk (OR=5.54, 95 % CI 2.75-11.19, p=0.00) than postmenopausal women when compared to women with more than 3 children. Binary logistic regression analysis revealed that low parity (≤3) substantially increased the risk for breast cancer (OR=4.80, 95% CI 2.34-9.85, p=0.00) in premenopausal women. CONCLUSION: Obesity, parity associated breast cancer risk and reduced breastfeeding cumulatively predispose the premenopausal women of this region to higher risk of breast cancer.
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Association of the -2518 A/G Polymorphism of MCP-1 with Breast Cancer in Punjab, North-West India.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. MATERIALS AND METHODS: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. RESULTS: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. CONCLUSIONS: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India.

No Association between the CCR5Δ32 Polymorphism and Sporadic Esophageal Cancer in Punjab, North-West India.

BACKGROUND: Chemokines and their receptors influence carcinogenesis and cysteine-cysteine chemokine receptor 5 (CCR5) directs spread of cancer to other tissues. A 32 base pair deletion in the coding region of CCR5 that might alter the expression or function of the protein has been implicated in a variety of immune-mediated diseases. The action of antiviral drugs being proposed as adjuvant therapy in cancer is dependent on CCR5 wild type status. In the present study, distribution of CCR5Δ32 polymorphism was assessed in North Indian esophageal cancer patients to explore the potential of using chemokine receptors antagonists as adjuvant therapy. MATERIALS AND METHODS: DNA samples of 175 sporadic esophageal cancer patients (69 males and 106 females) and 175 unrelated healthy control individuals (69 males and 106 females) were screened for the CCR5Δ32 polymorphism by direct polymerase chain reaction (PCR). RESULTS: The frequencies of wild type homozygous (CCR5/CCR5), heterozygous (CCR5/Δ32) and homozygous mutant (Δ32/Δ32) genotypes were 96.0 vs 97.72%, 4.0 vs 1.71% and 0 vs 0.57% in patients and controls respectively. There was no difference in the genotype and allele frequencies of CCR5Δ32 polymorphism in esophageal cancer patients and control group. CONCLUSIONS: The CCR5Δ32 polymorphism is not associated with esophageal cancer in North Indians. As the majority of patients express the wild type allele, there is potential of using antiviral drug therapy as adjuvant therapy.

Role of CT Colonography in Colonic Lesions and Its Correlation with Conventional Colonoscopic Findings.

BACKGROUND: Preoperative evaluation in patients with colorectal carcinoma is essential for a correct therapeutic plan. Conventional colonoscopy has certain limitations including its inability to detect synchronous lesions in case of distal obstructive mass and inaccurate tumour localization. CT colonography combines cross sectional imaging with virtual colonoscopic images and offers a comprehensive preoperative evaluation in patients with colorectal carcinoma including detection of synchronous lesions with accurate segmental localization and loco regional staging. AIM: The objective was to determine the role of CT colonography in various colonic lesions and to correlate the findings with conventional colonoscopy and histopathological findings. SETTINGS AND DESIGN: This prospective study included 50 patients with clinical symptoms suspicious of colonic pathology. MATERIALS AND METHODS: All the patients underwent both CT colonography and conventional colonoscopy on the same day. CT colonography was performed in supine and prone position. Considering histopathological and/or surgical findings as gold standard, sensitivity and specificity of both the modalities were calculated. RESULTS: Conventional colonoscopy missed two synchronous lesions proximal to occlusive mass and one lesion proximal to the anastomotic site; all were detected with CT colonography. One carpet lesion in rectum and one case of mild ulcerative colitis were missed by CT colonography. Sensitivity and specificity for detection of colorectal cancer were 97.56% and 100%, resp. with PPV and NPV of 100% and 93.75%, for CT colonography and 92.68% and 100%, respectively with PPV and NPV of 100% and 83.3% for conventional colonoscopy. Sensitivity for correct detection of acute and chronic ulcerative colitis of CT colonography was 66.6 % and 100 %, resp. CONCLUSION: CT colonography has higher sensitivity than conventional colonoscopy for detection of colorectal carcinoma, including its ability to detect abnormalities proximal to obstructing lesion, accurate segmental localization of lesions and staging. However, some limitations of CT colonography were difficulty in detection of flat lesions and lack of information about hyperemia and superficial mucosal erosion, where conventional colonoscopy scored over CT colonography.

Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians.

The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) -2578C/A, -2549I/D, -460T/C and -7C/T and VEGFR1 -710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of -2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55-4.92; p = 0.0005). VEGF -2578AA genotype (OR = 2.87; 95 % CI, 1.61-5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25-2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25-3.97) and C allele (OR = 1.42, 95 % CI, 1.07-1.87) of VEGF -460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF -7C/T and VEGFR1 -710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF -2549I/D and -2578C/A polymorphisms (Lewontin's [Formula: see text] = 0.99; r (2) = 0.97), -2549I/D and -460T/C ([Formula: see text] = 0.94; r (2) = 0.84), and -2578C/A and -460T/C polymorphisms ([Formula: see text] = 0.93; r (2) = 0.83). In the present study, we concluded that VEGF -2549I/D, -2578C/A and -460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.

No association of hypoxia inducible factor-1α gene polymorphisms with breast cancer in North-West Indians.

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1α) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-1α may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-1α with the risk of breast cancer in North Indian sporadic breast cancer patients. MATERIALS AND METHODS: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The CC and CA genotype frequency of HIF-1α g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-1α g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. CONCLUSIONS: The three HIF-1α polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.

Analysis of TP53 polymorphisms in North Indian sporadic esophageal cancer patients.

BACKGROUND: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. MATERIALS AND METHODS: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. RESULTS: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). CONCLUSIONS: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility.

Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in Punjabi population from North West India.

The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417 C/T (rs833062), -172 C/A (rs59260042), -165 C/T (rs79469752), -160 C/T, -152 G/A (rs13207351), -141 A/C (rs28357093) and -116 G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152 G/A polymorphism was 26.47 vs 38.34%, 46.08 vs 51.96%, and 27.45 vs 9.80%, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95%CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95%CI, 1.59-7.63, p = 0.001). For VEGF -116 G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47% and 34.8 vs 23.53% in patients and controls, respectively. Individuals having -116 AA genotype (OR = 3.40; 95%CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95%CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165 C/T and -141 A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63%; p = 0.002) and T allele (2.45 vs 9.31%; p = 0.003) of -165 C/T polymorphism among breast cancer patients as compared to controls. VEGF -141 A and C allele frequency were 96.57 vs 91.18% and 3.43 vs 8.82% in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95%CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95%CI, 0.15-0.89; p = 0.023) of -141 A/C polymorphism. We did not observe association of VEGF -417 T/C, -172 C/A, -160 C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152 G/A and -116 G/A polymorphisms were found to be significantly associated with increased risk for breast cancer while -165 C/T and -141 A/C polymorphisms were found to be associated with decreased risk for breast cancer in Punjabi population from North West India.