Aim: Breast cancer is the most common cancer in women both in the developed and less developed world. The reported study was designed to explore associations between hMSH2 - Gly322Asp (1032G>A, rs4987188) single nucleotide polymorphism (SNP) and the risk of breast carcinoma in the Polish women.
Material and methods: Blood samples were obtained from women with breast cancer (n=225), treated at the Department of Oncological Surgery and Breast Diseases, Polish Mother’s Memorial Hospital – Research Institute between the years 2005 and 2012. A control group included 220 cancer-free women. Genomic DNA was isolated and the SNP Gly322Asp of hMSH2 was determined by High-Resolution Melter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele.
Results: This study revealed that single nucleotide polymorphism Gly322Asp of hMSH2 is associated with both breast cancer risk and grading. Moreover, it can be linked with breast carcinoma tumor size and lymph node status. The Asp allele in patients may be a risk factor for breast carcinoma (OR 5.12; 95% CI 3.77 –6.97, p<.0001).
Conclusions: Gly322Asp single nucleotide polymorphism of hMSH2 may be a risk factor of breast cancer in the Polish women.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Low expression of the X-linked ribosomal protein S4 in human serous epithelia...Enrique Moreno Gonzalez
The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Low expression of the X-linked ribosomal protein S4 in human serous epithelia...Enrique Moreno Gonzalez
The X-linked ribosomal protein S4 (RPS4X), which is involved in cellular translation and proliferation, has previously been identified as a partner of the overexpressed multifunctional protein YB-1 in several breast cancer cells. Depletion of RPS4X results in consistent resistance to cisplatin in such cell lines.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
A KRAS-variant is a Biomarker of Poor Outcome, Platinum Chemotherapy Resistan...UCLA
Germ-line variants in the 3′ untranslated region (3′UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3′UTR of the KRAS oncogene, referred to as the KRAS-variant, is associated with both cancer risk and altered tumor biology. Here we test the hypothesis that the KRAS-variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS-variant positive EOC patients. As this variant appears to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival.
EOC patients with complete clinical data were genotyped for the KRAS-variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125), and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were employed to confirm altered sensitivity to chemotherapy with the KRAS-variant. The KRAS- variant was directly targeted through siRNA/miRNA oligonucleotides in cell lines and survival was measured.
Post-menopausal EOC patients with the KRAS-variant were significantly more likely to die of ovarian cancer by multivariate analysis (HR=1.67, 95% CI=1.09–2.57, p=0.019, n=279). Possibly explaining this finding, EOC patients with the KRAS-variant were significantly more likely to be platinum resistant (OR=3.18, CI=1.31–7.72, p=0.0106, n=291). Additionally, direct targeting of the KRAS-variant led to a significant reduction in EOC cell growth and survival in vitro.
These findings confirm the importance of the KRAS-variant in EOC, and indicate that the KRAS- variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this work supports the hypothesis that these tumors have continued dependence on such 3′UTR lesions, and that direct targeting may be a viable future treatment approach.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
Background and objective: Treatment of epithelial ovarian cancer (EOC) is a major challenge with only 30% 5-year survival rate. The outcome of the different therapeutic modalities is still poor, and there is an urgency to find new treatment lines. The effect of mesenchymal stem cells on different tumors is greatly variable. The present work shows the effect of cord blood mesenchymal stem cells conditioned media (MSC CM) in different concentrations on epithelial ovarian cancer stem cells (CD44+ cells) in vitro. Methodology: Ovarian cancer stem cells were subjected to MSC CM of (100%, 75%, 50%, 25%) concentrations for 72 hours followed by investigation of cell morphology, proliferation, apoptosis, cell cycle and expression of certain genes (Oct-4, Sox-2, and Nanog). Results: Cell shrinkage and cell debris was observed with all cancer cell lines by contrast with control. MTT assay showed a reduction in proliferation, in a concentration-dependent manner. The annexin-v results demonstrated a significant early and late apoptosis. There was an increase in the sub-G1 phase of the cell cycles indicating apoptosis. There was a progressive suppression of embryonic stemness genes in all cell lines compared to control. Conclusion: Based on these results, it was concluded that MSC CM may be a potential ovarian cancer inhibitor that may create a new modalities of treatment in ovarian cancer patients. Maher E. Elgaly | Mohamed E. El Ghareeb | Mohamed H. Bedairy | Ahmed M. Badawy | Abeer Shaaban | Farha El shennawy"Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovarian Cancer Cells in Vitro" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-5 , August 2018, URL: http://www.ijtsrd.com/papers/ijtsrd18182.pdf http://www.ijtsrd.com/other-scientific-research-area/other/18182/cord-blood-mesenchymal-stem-cells-conditioned-media-suppress-epithelial-ovarian-cancer-cells-in-vitro/maher-e-elgaly
The Single Nucleotide Polymorphisms (SNPS) of Vascular Endothelial Growth Fac...Agriculture Journal IJOEAR
Abstract—
Aim: The aim of the present work was to evaluate associations between the risk of endometriosis and -460C/T (rs833061) and +405G/C (rs2010963) polymorphisms in the VEGF gene.
Methodology: In the present study, we examined group of 100 patients with endometriosis and 100 controls. Genomic DNA was extracted from peripheral blood. Determination of genes polymorphic variants was made using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).
Results: Presented study showed statistically significant increase in the endometriosis development risk for the -460T/T genotype (OR 3.39; 95% CI, 1.60-7.13; p = 0.002) and for the -460T allele (OR 2.49; 95% CI, 1.64-3.78; p <.0001), as well as for the +405C/C genotype (OR 2.16; 95% CI, 1.047-4.48; p = 0.035) in patients with endometriosis in comparison with healthy control group. We also observed positive association of the +405C/C genotype (OR 0.26; 95% CI, 0.08-0.79; p = 0.019) as well as the +405C allele occurrence with an increased endometriosis development risk (OR 0.31; 95% CI, 0.19-0.71; p = 0.005), assessed by the degree of rASRM classification stages.
Conclusion: The results support the hypothesis that the -460C/T and +405G/C polymorphisms of the VEGF gene may be associated with endometriosis occurrence in Poland.
Keywords— endometriosis, genetic polymorphisms, VEGF.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
A KRAS-variant is a Biomarker of Poor Outcome, Platinum Chemotherapy Resistan...UCLA
Germ-line variants in the 3′ untranslated region (3′UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3′UTR of the KRAS oncogene, referred to as the KRAS-variant, is associated with both cancer risk and altered tumor biology. Here we test the hypothesis that the KRAS-variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS-variant positive EOC patients. As this variant appears to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival.
EOC patients with complete clinical data were genotyped for the KRAS-variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125), and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were employed to confirm altered sensitivity to chemotherapy with the KRAS-variant. The KRAS- variant was directly targeted through siRNA/miRNA oligonucleotides in cell lines and survival was measured.
Post-menopausal EOC patients with the KRAS-variant were significantly more likely to die of ovarian cancer by multivariate analysis (HR=1.67, 95% CI=1.09–2.57, p=0.019, n=279). Possibly explaining this finding, EOC patients with the KRAS-variant were significantly more likely to be platinum resistant (OR=3.18, CI=1.31–7.72, p=0.0106, n=291). Additionally, direct targeting of the KRAS-variant led to a significant reduction in EOC cell growth and survival in vitro.
These findings confirm the importance of the KRAS-variant in EOC, and indicate that the KRAS- variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this work supports the hypothesis that these tumors have continued dependence on such 3′UTR lesions, and that direct targeting may be a viable future treatment approach.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
Background and objective: Treatment of epithelial ovarian cancer (EOC) is a major challenge with only 30% 5-year survival rate. The outcome of the different therapeutic modalities is still poor, and there is an urgency to find new treatment lines. The effect of mesenchymal stem cells on different tumors is greatly variable. The present work shows the effect of cord blood mesenchymal stem cells conditioned media (MSC CM) in different concentrations on epithelial ovarian cancer stem cells (CD44+ cells) in vitro. Methodology: Ovarian cancer stem cells were subjected to MSC CM of (100%, 75%, 50%, 25%) concentrations for 72 hours followed by investigation of cell morphology, proliferation, apoptosis, cell cycle and expression of certain genes (Oct-4, Sox-2, and Nanog). Results: Cell shrinkage and cell debris was observed with all cancer cell lines by contrast with control. MTT assay showed a reduction in proliferation, in a concentration-dependent manner. The annexin-v results demonstrated a significant early and late apoptosis. There was an increase in the sub-G1 phase of the cell cycles indicating apoptosis. There was a progressive suppression of embryonic stemness genes in all cell lines compared to control. Conclusion: Based on these results, it was concluded that MSC CM may be a potential ovarian cancer inhibitor that may create a new modalities of treatment in ovarian cancer patients. Maher E. Elgaly | Mohamed E. El Ghareeb | Mohamed H. Bedairy | Ahmed M. Badawy | Abeer Shaaban | Farha El shennawy"Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovarian Cancer Cells in Vitro" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-5 , August 2018, URL: http://www.ijtsrd.com/papers/ijtsrd18182.pdf http://www.ijtsrd.com/other-scientific-research-area/other/18182/cord-blood-mesenchymal-stem-cells-conditioned-media-suppress-epithelial-ovarian-cancer-cells-in-vitro/maher-e-elgaly
The Single Nucleotide Polymorphisms (SNPS) of Vascular Endothelial Growth Fac...Agriculture Journal IJOEAR
Abstract—
Aim: The aim of the present work was to evaluate associations between the risk of endometriosis and -460C/T (rs833061) and +405G/C (rs2010963) polymorphisms in the VEGF gene.
Methodology: In the present study, we examined group of 100 patients with endometriosis and 100 controls. Genomic DNA was extracted from peripheral blood. Determination of genes polymorphic variants was made using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).
Results: Presented study showed statistically significant increase in the endometriosis development risk for the -460T/T genotype (OR 3.39; 95% CI, 1.60-7.13; p = 0.002) and for the -460T allele (OR 2.49; 95% CI, 1.64-3.78; p <.0001), as well as for the +405C/C genotype (OR 2.16; 95% CI, 1.047-4.48; p = 0.035) in patients with endometriosis in comparison with healthy control group. We also observed positive association of the +405C/C genotype (OR 0.26; 95% CI, 0.08-0.79; p = 0.019) as well as the +405C allele occurrence with an increased endometriosis development risk (OR 0.31; 95% CI, 0.19-0.71; p = 0.005), assessed by the degree of rASRM classification stages.
Conclusion: The results support the hypothesis that the -460C/T and +405G/C polymorphisms of the VEGF gene may be associated with endometriosis occurrence in Poland.
Keywords— endometriosis, genetic polymorphisms, VEGF.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Increased Expression of GNL3L is Associated with Aggressive Phenotypes in Col...JohnJulie1
Guanine nucleotide binding protein-like 3-like (GNL3L) plays critical roles in development and progression of several types of human cancers. However, the function and clinical significance of GNL3L in colorectal cancer (CRC) remain unclear. In this study, the effect of GNL3L in CRC and its underlying mechanism were investigated.
Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: effica...Enrique Moreno Gonzalez
Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in
China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and
migration of endothelial cells and some types of tumor cells. In this study, we evaluated the
efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant
chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II
trial.
Study on Histopathological Correlation with ER, PR, and HER 2 Neu Receptor Status in Breast Carcinoma and its Prognostic Importance
Mahendra Singh, Jagdish Kumar*, Anita Omhare, Vandana Mishra, Chayanika Kala
http://dx.doi.org/10.21276/SSR-IIJLS.2019.5.1.3
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical Prostatectomy
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the
predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical
Prostatectomy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
"Understanding the Carbon Cycle: Processes, Human Impacts, and Strategies for...MMariSelvam4
The carbon cycle is a critical component of Earth's environmental system, governing the movement and transformation of carbon through various reservoirs, including the atmosphere, oceans, soil, and living organisms. This complex cycle involves several key processes such as photosynthesis, respiration, decomposition, and carbon sequestration, each contributing to the regulation of carbon levels on the planet.
Human activities, particularly fossil fuel combustion and deforestation, have significantly altered the natural carbon cycle, leading to increased atmospheric carbon dioxide concentrations and driving climate change. Understanding the intricacies of the carbon cycle is essential for assessing the impacts of these changes and developing effective mitigation strategies.
By studying the carbon cycle, scientists can identify carbon sources and sinks, measure carbon fluxes, and predict future trends. This knowledge is crucial for crafting policies aimed at reducing carbon emissions, enhancing carbon storage, and promoting sustainable practices. The carbon cycle's interplay with climate systems, ecosystems, and human activities underscores its importance in maintaining a stable and healthy planet.
In-depth exploration of the carbon cycle reveals the delicate balance required to sustain life and the urgent need to address anthropogenic influences. Through research, education, and policy, we can work towards restoring equilibrium in the carbon cycle and ensuring a sustainable future for generations to come.
Willie Nelson Net Worth: A Journey Through Music, Movies, and Business Venturesgreendigital
Willie Nelson is a name that resonates within the world of music and entertainment. Known for his unique voice, and masterful guitar skills. and an extraordinary career spanning several decades. Nelson has become a legend in the country music scene. But, his influence extends far beyond the realm of music. with ventures in acting, writing, activism, and business. This comprehensive article delves into Willie Nelson net worth. exploring the various facets of his career that have contributed to his large fortune.
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Introduction
Willie Nelson net worth is a testament to his enduring influence and success in many fields. Born on April 29, 1933, in Abbott, Texas. Nelson's journey from a humble beginning to becoming one of the most iconic figures in American music is nothing short of inspirational. His net worth, which estimated to be around $25 million as of 2024. reflects a career that is as diverse as it is prolific.
Early Life and Musical Beginnings
Humble Origins
Willie Hugh Nelson was born during the Great Depression. a time of significant economic hardship in the United States. Raised by his grandparents. Nelson found solace and inspiration in music from an early age. His grandmother taught him to play the guitar. setting the stage for what would become an illustrious career.
First Steps in Music
Nelson's initial foray into the music industry was fraught with challenges. He moved to Nashville, Tennessee, to pursue his dreams, but success did not come . Working as a songwriter, Nelson penned hits for other artists. which helped him gain a foothold in the competitive music scene. His songwriting skills contributed to his early earnings. laying the foundation for his net worth.
Rise to Stardom
Breakthrough Albums
The 1970s marked a turning point in Willie Nelson's career. His albums "Shotgun Willie" (1973), "Red Headed Stranger" (1975). and "Stardust" (1978) received critical acclaim and commercial success. These albums not only solidified his position in the country music genre. but also introduced his music to a broader audience. The success of these albums played a crucial role in boosting Willie Nelson net worth.
Iconic Songs
Willie Nelson net worth is also attributed to his extensive catalog of hit songs. Tracks like "Blue Eyes Crying in the Rain," "On the Road Again," and "Always on My Mind" have become timeless classics. These songs have not only earned Nelson large royalties but have also ensured his continued relevance in the music industry.
Acting and Film Career
Hollywood Ventures
In addition to his music career, Willie Nelson has also made a mark in Hollywood. His distinctive personality and on-screen presence have landed him roles in several films and television shows. Notable appearances include roles in "The Electric Horseman" (1979), "Honeysuckle Rose" (1980), and "Barbarosa" (1982). These acting gigs have added a significant amount to Willie Nelson net worth.
Television Appearances
Nelson's char
UNDERSTANDING WHAT GREEN WASHING IS!.pdfJulietMogola
Many companies today use green washing to lure the public into thinking they are conserving the environment but in real sense they are doing more harm. There have been such several cases from very big companies here in Kenya and also globally. This ranges from various sectors from manufacturing and goes to consumer products. Educating people on greenwashing will enable people to make better choices based on their analysis and not on what they see on marketing sites.
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hMSH2 Gly322Asp (rs4987188) Single nucleotide polymorphism and the risk of breast cancer in the Polish women
1. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-8, August- 2016]
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hMSH2 Gly322Asp (rs4987188) Single nucleotide polymorphism
and the risk of breast cancer in the Polish women
Hanna Romanowicz1
, Jan Bieńkiewicz2
, Marek Zadrożny3
, Tomasz Szaflik4
, Beata
Smolarz5
1
Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Rzgowska 281/289, 93-338 Lodz, Poland
hanna-romanowicz@wp.pl
2
Department of Surgical, Endoscopic and Oncologic Gynaecology, Institute of Polish Mother’s Memorial Hospital,
Rzgowska 281/289, 93-338 Lodz, Poland
bjanek2@gmail.com
3
Department of Oncological Surgery and Breast Diseases, Polish Mother's Memorial Hospital - Research Institute, Rzgowska
281/289, 93-338 Lodz, Poland
zadrozny.lodz@wp.pl
4
Department of Operative Gynaecology, Polish Mother's Memorial Hospital - Research Institute, Rzgowska 281/289, 93-338
Lodz, Poland
tomaszszaflik@gmail.com
5
Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Rzgowska
281/289, 93-338 Lodz, Poland
smolbea@wp.pl
Abstract—
Aim: Breast cancer is the most common cancer in women both in the developed and less developed world. The reported study
was designed to explore associations between hMSH2 - Gly322Asp (1032G>A, rs4987188) single nucleotide polymorphism
(SNP) and the risk of breast carcinoma in the Polish women.
Material and methods: Blood samples were obtained from women with breast cancer (n=225), treated at the Department of
Oncological Surgery and Breast Diseases, Polish Mother’s Memorial Hospital – Research Institute between the years 2005
and 2012. A control group included 220 cancer-free women. Genomic DNA was isolated and the SNP Gly322Asp of hMSH2
was determined by High-Resolution Melter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
for each genotype and allele.
Results: This study revealed that single nucleotide polymorphism Gly322Asp of hMSH2 is associated with both breast
cancer risk and grading. Moreover, it can be linked with breast carcinoma tumor size and lymph node status. The Asp allele
in patients may be a risk factor for breast carcinoma (OR 5.12; 95% CI 3.77 –6.97, p<.0001).
Conclusions: Gly322Asp single nucleotide polymorphism of hMSH2 may be a risk factor of breast cancer in the Polish
women.
Keywords— breast cancer, single nucleotide polymorphism, hMSH2, mismatch repair genes.
I. INTRODUCTION
Carcinoma of the breast is the most common cause of death among women worldwide. 1.7 million of new cases was
diagnosed in 2012. Same year half a million women died due to breast cancer (GLOBOCAN 2012: Estimated Cancer
Incidence, Mortality and Prevalence Worldwide in 2012). Every year over 17 thousand women in Poland are diagnosed with
breast cancer with more than 5 thousand of them eventually succumbing to the illness [i].
According to authors of “White Book. Overcoming colorectal and breast cancer in Poland in comparison to other European
countries” by 2020 the incidence should increase to almost 20 thousand patients yearly [2]. 5year survival rate among breast
cancer patients in Poland is one of the lowest in whole Europe. Analyzing European average survival rate of breast cancer
patients versus Poland rate, in first year after diagnose the values are 4% lower, and after 5 years they rise to 10%
(EUROCARE5, online database – years 2000–2007).
The system of DNA repair takes part in maintaining the genomic integrity which undergoes changes under exo- and
endogenous factors. In man, the protein products of genes are directly involved in the repair process, taking part in several
2. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-8, August- 2016]
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repair systems. The repair process usually encompasses two stages: the excision of lesion and the repair synthesis. This is
how repair system act via base-excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR).
Totally converse is the repair system activity by direct lesion reversal, in which there is merely a single-stage process with
maintained integrity of the DNA phosphodiester chain and the system of recombination repair (HR). Defects of the proteins,
which directly participate in DNA repair and its control, are associated with an increased susceptibility to malignant changes.
The alternations in the oncogenes and tumor suppressor genes as well as DNA mismatch repair genes have been associated
with cancers development [3, 4, 5]. There are seven major DNA mismatch repair genes in humans: MLH1, MLH3, PMS1,
PMS2, MSH2, MSH3 and MSH6. hMSH2, also known as MutS protein homolog 2, is a tumor suppressor gene that encodes a
protein which plays a crucial role in DNA mismatch repair, but also holds activity in other versatile types of DNA repair
such as: homologous recombination, transcription-coupled repair or even base excision repair. Microsatellite instability,
which is a notorious effect of hMSH2 mutations, is also an axis feature of Hereditary Nonpolyposis Colorectal Cancer
(HNPCC) alias Lynch syndrome [6].
State-of-the-art research focuses on the analysis of versatile genetic aspects and on the attempt to associate these with clinical
manifestation of carcinogenesis. Large effort has been lately put into investigation of single nucleotide polymorphisms
(SNPs), which may underline the differences in ones susceptibility and natural history of diseases. According to NCBI
dbSNP there are more than 150 million SNPs in human already discovered [7] and as many as 380 SNPs in hMSH2 only [8].
A positive correlation between polymorphisms of the hMSH2 gene and occurrence of cancer was reported in colorectal
cancer [9, 10], gastroesophageal cancer [11, 12], lung cancer [13] or even gallbladder cancer [14]. In addition,
polymorphisms of hMSH2 may also have en effect on cellular response to radiation therapy in breast cancer patients [15].
Gly322Asp (1032G>A, rs4987188) is a missense SNP resulting in a Glycine to Aspartic Acid switch at codon 322. However
the role of hMSH2 polymorphism and breast cancer development is still unknown. The primary goal of the study was an
identification of genetic variants which increase the risk of breast cancer in the population of Polish women.
II. MATERIALS AND METHODS
2.1 Patients
Blood samples from patients with breast cancer (n=225) treated in the Department of Oncological Surgery and Breast
Diseases, Polish Mother’s Memorial Hospital – Research Institute between 2005-2012 were selected to the test group the
study. All the tumors were graded by a method, based on the criteria of Scarf-Bloom-Richardson. The age of the patients
ranged in from 38 to 85 (mean age: 54.2 ± 9.11). Controls consisted of the DNA extracted from blood samples from age-
matched 440 cancer-free women (age range: 35–83, mean age: 52.27±10.16). The full clinicopathological characteristics of
the study group are presented in Table 1.
TABLE 1
THE CLINICOPATHOLOGICAL CHARACTERISTICS OF 225 PATIENTS WITH BREAST CANCER
Characteristics Number of patients (%)
Lymph node status
N0
N1
N2
N3
80 (35%)
90 (40%)
40 (18%)
15 (7%)
Tumor size grade
T1
T2
T3
64 (28%)
149 (66%)
12 (48%)
Bloom-Richardson grading
I
II
III
49 (22%)
166 (74%)
10 (4%)
3. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-8, August- 2016]
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All of the studied individuals were Caucasians and constituted a homogenous population from the same ethnic and
geographical origins. Genetic studies were performed at the Laboratory of Cancer Genetics, Department of Clinical
Pathomorphology, Institute of the Polish Mother’s Memorial Hospital in Lodz, Poland. The study was approved by the
Research Ethics Committee at the Polish Mother’s Memorial Hospital Research Institute (Approval number, No 10/2012).
2.2 DNA isolation
Genomic DNA was obtained using DNeasy Blood & Tissue Kit (Qiagen GmbH, Hilden, Germany) according to the
manufacturer instruction.
2.3 Determination of hMSH2 genotype
Polymorphism Gly322Asp of the hMSH2 gene was determined by High-Resolution Melter analysis. The analysis of the
SNPs was performed with support of a Light Cycler®
480 High Resolution Melting Master Kit (Roche, Mannheim,
Germany), according to the manufacturer’s recommendations. A non-template control contained water, instead of genomic
DNA, as a negative control. Additionally, positive controls (DNA samples with known genotype) were employed in each run
of HRM analysis. All PCR was carried out in a LightCycler®
96 (Roche, Mannheim, Germany) Thermocycler. The collected
data were analysed, using the LightCycler®
96 software version SW 1.1 (Roche, Mannheim, Germany).
2.4 Statistical Analysis
A standard χ2-test was used to assess the departure from Hardy-Weinberg equilibrium in the analysed SNP. Genotype and
allele frequencies in patients and controls were correlated by χ2-test. The general risks were illustrated as odds ratios (ORs)
with associated 95% intervals (CIs) by unconditional logistic regression. P-values < 0.05 were considered significant.
III. RESULTS
All the recruited breast cancer subjects and control were successfully genotyped for the hMSH2 polymorphisms. From the
PCR analysis, all patients were classified into three genotypes of the hMSH2 polymorphism: Gly/Gly, Gly/Asp and Asp/Asp.
In case of the Gly322Asp polymorphism of hMSH2 gene the distribution of the genotypes in the patients differed
significantly from one expected from the Hardy-Weinberg equilibrium (p < 0.05). The observed genotype frequency of
Gly322Asp polymorphism in the controls group were in agreement with Hardy-Weinberg equilibrium (p>0.05). It is caused
by the very low abundance of the Gln/Gln genotype in the examined population of Polish women.
The study of a series of 225 DNA samples from the test group followed by a comparison with controls revealed a
relationship of the studied SNP with the risk of breast cancer (Table 2).
TABLE 2
DISTRIB0075TIONS OF GLY/GLY, GLY/ASP AND ASP/ASP GENOTYPES AND GLY AND ASP ALLELES OF THE
Gly322Asp POLYMORPHISM OF hMSH2 GENE IN THE GROUP OF BREAST CANCER PATIENTS AND CONTROLS.
Patients
(n = 225)
Controls
(n = 220)
hMSH2- Gly322Asp Number (%) Number (%) OR (95% CI)a
Pb
Gly/Gly 25 11 44 20 1.00 Ref
Gly/Asp 28 12 140 64 0.35 (0.181-0.66) 0.001
Asp/Asp 172 77 36 16 8.41 (4.57-15.44) <.0001
Gly 78 17 228 52 1.00 Ref
Asp 372 83 212 48 5.12 (3.77-6.97) <.0001
a
Crude odds ratio (OR), 95 % CI = confidence interval at 95 %, b
Chi square
We have proven that Asp variant may increase the risk of cancer (OR 5.12; 95% CI 3.77 –6.97, p<.0001). Moreover, we
observed that Asp/Asp genotype was strongly associated with the risk of breast carcinoma (OR 8.41; 95% CI 4.57 – 15.44,
p<.0001). Furthermore, an association was observed between the studied polymorphism and cancer grading (Table 3): Grade
1 (G1) patients generally demonstrated higher frequencies of Gly/Asp heterozygotes (p=0.039). Additionally, the studied
SNP was statistically related to tumor size and lymph node status (Table 4).
4. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-8, August- 2016]
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TABLE 3
DEPENDENCE OF hMSH2 GENE POLYMORPHISM GENOTYPES AND ALLELE FREQUENCY ON TUMOUR GRADE
IN BREAST CANCER PATIENTS
a
breast cancer patients
gradeb
GI (n = 49) GII + GIII (n = 176) OR (95% CI)c
p
hMSH2- Gly322Asp Number (%) Number (%)
Gly/Gly 9 (18) 16 (9) 1.00 Ref
Gly/Asp 18 (37) 10 (6) 3.20 (1.04-9.85) 0.039
Asp/Asp 22 (45) 150 (85) 0.26 (0.10-0.66) 0.006
Gly 36 (37) 42 (12) 1.00 Ref
Asp 62 (63) 310 (88) 0.23 (0.13 – 0.39) <.0001
a
n =450; b
according to Scarf-Bloom-Richardson criteria
TABLE 4
hMSH2 GENE POLYMORPHISM AND BREAST CANCER PROGRESSION
a
T T1 (n=64) T2+T3 (n=161) OR (95% CI)b
pc
number (%) number (%)
Gly/Gly 15 23 10 6 1.00 Ref. -
Gly/Asp 10 16 18 11 0.37 (0.12-1.12) 0.135
Asp/Asp 39 61 133 83 0.19 (0.08-0.46) 0.0002
Gly 40 31 38 12 1.00 Ref. -
Asp 88 69 284 88 0.29 (0.17-0.48) <.0001
N N- (n=80) N+ (n=145) OR (95% CI) p
number (%) number (%)
Gly/Gly 11 14 14 10 1.00 Ref. -
Gly/Asp 18 23 10 7 2.29 (0.75-6.91) 0.228
Asp/Asp 51 63 121 83 0.53 (0.22-1.26) 0.225
Gly 40 25 38 13 1.00 Ref. -
Asp 120 75 252 87 0.45 (0.27-0.74) 0.002
a
T1 vs. T2 + T3, b
N - (node negative) vs. N + (node positive), b
Crude odds ratio (OR), 95 % CI = confidence interval at
95%, c
Chi square
IV. DISCUSSION
The genes of the DNA lesion repair systems play the key role in maintaining the genome integrity and control the repair of
mutation-affected DNA. Without the genes, DNA would continue the accumulation of errors which would within a short
time prevent further cell survival. Proper DNA repair ensures genomic integrity and plays a significant role in its protection
against effects of carcinogenic factors. The polymorphism of repair genes may influence the performance of the process, by
which defects of genetic material are removed, thus influencing the individual susceptibility to formation of neoplastic
disease.
Defective DNA mismatch repair that results in microsatellite instability (MSI) is the axis feature of Lynch Syndrome, which
is characterized by increased hereditary incidence of colorectal, ovarian and endometrial cancers [16]. MSI itself is defined
by changes in the lengths of dinucleotide repeats – mostly cytosine and adenine. Almost 60% HNPCC families carry the
burden of genetic alterations in hMSH2. Although only a minimal share of all abovementioned cancers are directly linked
with classical Lynch Syndrome [18], almost 86% of the entire breast cancer population shows a substantial loss in expression
of DNA mismatch repair genes [16].
There were more than 130 DNA repair genes identified, in which a series of single nucleotide polymorphisms (SNPs) were
discovered. In order to define the role, which may be played by these variants in modulating the risk of cancer formation, it
is necessary to define their functional significance. The variability, perceived in DNA repair genes, may be of clinical
importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy [17]. Literature
data suggest that genetic variation of hMSH2 gene may increase the risk of ovarian, breast and endometrial cancers [18, 19].
In our study we have demonstrated that both the Asp allele and the polymorphic homozygote Asp/Asp of the analysed SNP
strongly increase the risk of breast carcinoma. Interestingly, these results are not consistent with the analysis of the SNP
5. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-8, August- 2016]
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Gly322Asp of hMSH2 in breast cancer, where the Asp allele demonstrated rather a weak protective role or no clinical
significance at all [19, 20]. Additionally, a correlation has been found between the studied polymorphism and cancer grading:
G1 was statistically associated with Gly/Asp heterozygotes. The study revealed that SNP Gly322Asp of hMSH2 could be
correlated with tumor size and lymph node status of breast cancer.
Our study, however, has certain limitations: patients group and controls may be quantitatively unsatisfactory. Among the
abundance of genetic polymorphisms in versatile MMR genes only one polymorphism of hMSH2 was here analysed without
respect to linkage disequilibrium (LD), which is a crucial feature of population genetics. A joint analysis of single nucleotide
polymorphism Gly322Asp of hMSH2 and other SNPs in DNA mismatch repair genes could shed a new light on the role of
SNPs in breast cancer.
V. CONCLUSIONS
The obtained results demonstrate a possibility of a relationship between the Gly322Asp polymorphism of hMSH2 and breast
cancer in the population of the Polish women. However, it requires further studies on much larger groups of patients.
CONFLICT OF INTEREST
Authors declare no conflict of interest
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