MMP1 1G/2G promoter polymorphism and risk of esophageal adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10555-10555
Author(s):  
S. Singh ◽  
K. Asomaning ◽  
M. H. Kulke ◽  
W. Zhou ◽  
R. Zhai ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Smoking Status ◽  
Gastroesophageal Junction ◽  
Promoter Polymorphism ◽  
Oral Cancers ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
And Gender ◽  
Risk Of Cancer

10555 Background: The 2G allele of the MMP1 -1607 1G/2G promoter polymorphism creates an Ets binding site that leads to increased transcriptional and enzyme activity, particularly in the presence of growth factors and cytokines. This polymorphism has been associated with greater risk of cancer (e.g., renal cell, lung and oral cancers, glioblastomas) and cancer invasiveness (e.g., melanoma, cervical, lung and colorectal cancer). The aim of the current study was to evaluate the role of this MMP 1G/2G polymorphism in the risk of esophageal adenocarcinoma (EA). Methods: We evaluated 323 histologically confirmed EA cases and 464 healthy controls frequency-matched for age and gender. Genotyping of the MMP1 1G/2G promoter polymorphism involved a Taqman approach. All EAs had endoscopic evidence showing that the center of the tumors were located at or above the gastroesophageal junction. Odds Ratios (OR) were calculated using multivariate logistic regression, adjusted for age, gender, smoking status, and body-mass index (BMI) at the age of 18 years (to represent a healthy adult BMI). Results: Genotype frequencies were: 33% (1G/1G), 47% (1G/2G) & 20% (2G/2G) in controls; in cases, 26% (1G/1G), 50% (1G/2G) & 24% (2G/2G). 88% of cases were male. The MMP1 2G/2G and 1G/2G genotypes conferred a greater risk of EA, with adjusted ORs of 1.50 (95%CI=1.0–2.3) and 1.34 (95%CI=0.9–1.9), respectively, when compared with the wildtype 1G/1G genotype. The 2G allele (2G/2G + 1G/2G) conferred an adjusted OR of 1.38 (95%CI=1.0–1.9). By stage, the adjusted ORs for the 2G allele were 1.26 (95%CI=0.8–2.1), 1.45 (95%CI=0.9–2.3), & 1.54 (95%CI=0.9–2.7) for node negative, node-positive, and metastatic disease, respectively. Conclusions: The 2G allele of the MMP1 -1607 1G/2G polymorphism was associated with an increased risk of EA in this analysis. In addition, there was a non-significant trend towards conferring greater risk in the more advanced stages of EA, suggesting a possible role of this polymorphism in the invasiveness of this cancer. No significant financial relationships to disclose.

scholarly journals Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

2019 ◽  
Vol 31 (1) ◽  
pp. 1-11
Author(s):  
R. Stephen McCain ◽  
Damian T. McManus ◽  
Stephen McQuaid ◽  
Jacqueline A. James ◽  
Manuel Salto-Tellez ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Cigarette Smoking ◽  
Esophageal Adenocarcinoma ◽  
Alcohol Intake ◽  
Smoking Status ◽  
Glut 1 ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Cancer

Abstract Purpose To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. Methods A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. Results In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13–3.38) but not adjusted (HR 1.70 95% CI 0.95–3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. Conclusions In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival.

scholarly journals THE ROLE OF INTERLEUKIN 1β GENE POLYMORPHISM IN DEVELOPMENT OF PREDOMINANTY SENSORY CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

2019 ◽  
Vol 21 (1) ◽  
pp. 141-148
Author(s):  
T. E. Popova ◽  
N. A. Shnayder ◽  
M. M. Petrova ◽  
A. A. Tappakhov
Keyword(s):  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Study Groups ◽  
Krasnoyarsk Region ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Disease ◽  
T Locus ◽  
Il1b Gene

The aim of the present study was a search for associations between the polymorphic allelic variants 3954 C>T (rs1143644) and -511C>T (rs16944) of IL1B gene in the patients with sensory predominant chronic inflammatory demyelinating polyneuropathies (SP-CIDP) from Krasnoyarsk Region and the Sakha (Yakutia) Republic. A total of 95 people were examined, having been divided into 2 groups according to their residence. The first group consisted of 42 patients living in the Sakha (Yakutia) Republic. The second group included 53 patients living in the Krasnoyarsk Region. It was revealed that the carriers of homozygous CC genotype in the 3954C>T locus were more often detected in patients from the Sakha (Yakutia) Republic, and the carriage of TT genotype is found exclusively in the patients from Krasnoyarsk Region. When comparing the different genotype frequencies in the -511CT locus, we did not reveal any statistically significant differences between the two groups of patients. Presence of the CC genotype of the 3954C>T locus was associated with a significantly increased risk of disease in the patients from Sakha (Yakutia) Republic, while carrying CT and TT genotypes at the locus 3954C>T and the TT genotype at the locus -511C>T, is associated with increased risk disorder among patients of the Krasnoyarsk Region. The frequency of carriage of various genotypes in the 3954C>T and -511C>T loci of the IL1B gene was prevalent among the patients from the Sakha (Yakutia) Republic, the association of genotypes of CC/CT prevailed in patients from the Krasnoyarsk Region (p = 0.005), as well as prevalence of CC/CC and CC/CT (p = 0.023). However, there was no statistically significant difference in occurrence of individual genotypes between the two study groups. When analyzing the carrier frequency of high-producing alleles of 3954C and -511C in patients with SP-CIDP, it was shown that they were significantly more common among patients from the Sakha (Yakutia) Republic and patients from the Krasnoyarsk Region than the low-producing 3954T and -511T alleles. Moreover, the 3954C allele was more often found in the Yakut group (p = 0.001), and in the -511C allele for the Krasnoyarsk group of patients (p = 0.05). The presence of 3954C and -511C alleles increases the risk of SP-CIDP development in patients from the Sakha (Yakutia) Republic, as well as carriage of 3954T allele in patients from the Krasnoyarsk Region.

Abstract WP164: Role of Risk Factors in the Paradoxical Effect of Smoking on Peri-procedural Stroke in SAMMPRIS

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christine A Holmstedt ◽  
Tanya N Turan ◽  
Michael J Lynn ◽  
Bethany F Lane ◽  
Jean Montgomery ◽  
...  
Keyword(s):  
Risk Factors ◽  
Odds Ratio ◽  
Multivariate Analyses ◽  
Smoking Status ◽  
Active Form ◽  
Intracranial Stenosis ◽  
Contributory Factor ◽  
Increased Risk ◽  
Never Smokers

Background: A previous SAMMPRIS analysis of patients randomized to stenting showed that peri-procedural ischemic infarcts were significantly associated with diabetes, basilar stenosis, age, and smoking status with never smokers having a higher risk (odds ratio = 8.8, p< 0.001). We sought to determine if this finding could be due to a higher burden of other risk factors in never smokers. Method: Baseline features in 213 patients undergoing stenting in SAMMPRIS were compared between never smokers vs. former and current smokers in univariate and multivariate analyses. Logistic regression was used to determine the effect of smoking on peri-procedural ischemic infarcts after adjusting for factors related to smoking. Data: Univariate results are shown in Table 1. Never smokers were significantly (P<0.05) more likely to be female, diabetic, hypertensive, and have another intracranial stenosis, but in multivariate analyses only hypertension and another intracranial stenosis remained significantly (P<0.05) associated with smoking status. In a multivariate model that incorporated hypertension and another intracranial stenosis along with smoking status, diabetes, basilar stenosis, and age, smoking status remained significant with an increased risk among patients who never smoked (odds ratio = 5.3, p = 0.005). Conclusion: While never smokers had significantly higher rates of some risk factors compared to active or previous smokers, these risk factors do not explain all the increased risk of early stroke in never smokers after stenting in SAMMPRIS. Another contributory factor may be that smoking accelerates the conversion of clopidogrel to its active form.

Transitions to adulthood and psychological distress in young adults born 12 years apart: constraints on and resources for development

2009 ◽  
Vol 40 (2) ◽  
pp. 301-313 ◽  
Author(s):  
A. Sacker ◽  
N. Cable
Keyword(s):  
Young Adults ◽  
Psychological Distress ◽  
Social Class ◽  
Transition To Adulthood ◽  
Well Being ◽  
Structural Constraints ◽  
Increased Risk ◽  
And Gender ◽  
Adult Roles

BackgroundLater transitions to adult roles and responsibilities have been linked with better psychological well-being yet psychological distress has risen despite young people making the transition to adulthood at older ages over recent years.MethodWe examine the role of structural constraints and adolescent resources in the relationship between the timing of transitions and psychological distress in early adult life in the 1958 National Child Development Study and the 1970 British Cohort Study. Graphical chain models were used to examine the influences on timing of four key transitions and their relationship with psychological distress (Malaise Inventory). The role of structural factors at birth (gender, social class) and adolescent resources (psychosocial problems, exam grades) were modelled.ResultsAn earlier transition to adult roles was associated with an increased risk for psychological distress but so was failing to make some key transitions. Structural constraints had negative effects on successful development. Persistent social class and gender inequalities in psychological distress were evident in both cohorts. Social class constraints were mediated by educational resources whereas gender constraints were mediated by psychosocial resources. The influence of structural constraints on the timing of transitions to adult roles was more complex with evidence of positive and negative mediation and moderation effects.ConclusionsDelaying transition to adulthood promotes psychological health but failure of transition to independent living is associated with psychological distress. Life-course transitions are constrained by social origin and gender and possibly economic environment. Adolescent resources help young adults to make timely transitions to adult roles.

Recent Evidence on the Role of Dietary PUFAs in Cancer Development and Prevention

2018 ◽  
Vol 25 (16) ◽  
pp. 1818-1836 ◽  
Author(s):  
Massimo D`Archivio ◽  
Beatrice Scazzocchio ◽  
Rosaria Vari ◽  
Carmela Santangelo ◽  
Claudio Giovannini ◽  
...  
Keyword(s):  
Human Health ◽  
Scientific Evidence ◽  
Beneficial Effects ◽  
Tumor Subtypes ◽  
Human Cancers ◽  
Increased Risk ◽  
Food And Nutrition ◽  
Risk Of Cancer

Background: Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. Methods: We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Results: Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. Conclusion: N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.

scholarly journals Role of Nitrative and Oxidative DNA Damage in Inflammation-Related Carcinogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Mariko Murata ◽  
Raynoo Thanan ◽  
Ning Ma ◽  
Shosuke Kawanishi
Keyword(s):  
Oxidative Dna Damage ◽  
Promoter Hypermethylation ◽  
Physical Factors ◽  
Barr Virus ◽  
Dna Base ◽  
Increased Risk ◽  
Epstein Barr ◽  
Cancer Tissues ◽  
Risk Of Cancer

Chronic inflammation induced by biological, chemical, and physical factors has been found to be associated with the increased risk of cancer in various organs. We revealed that infectious agents including liver fluke,Helicobacter pylori, and human papilloma virus and noninfectious agents such as asbestos fiber induced iNOS-dependent formation of 8-nitroguanine and 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG) in cancer tissues and precancerous regions. Our results with the colocalization of phosphorylated ATM andγ-H2AX with 8-oxodG and 8-nitroguanine in inflammation-related cancer tissues suggest that DNA base damage leads to double-stranded breaks. It is interesting from the aspect of genetic instability. We also demonstrated IL-6-modulated iNOS expression via STAT3 and EGFR in Epstein-Barr-virus-associated nasopharyngeal carcinoma and found promoter hypermethylation in several tumor suppressor genes. Such epigenetic alteration may occur by controlling the DNA methylation through IL-6-mediated JAK/STAT3 pathways. Collectively, 8-nitroguanine would be a useful biomarker for predicting the risk of inflammation-related cancers.

scholarly journals The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid

2012 ◽  
Vol 302 (8) ◽  
pp. G864-G872 ◽  
Author(s):  
Heather B. Roesly ◽  
Mohammad R. Khan ◽  
Hwu Dau Rw Chen ◽  
Kimberly A. Hill ◽  
Nirushan Narendran ◽  
...  
Keyword(s):  
Bile Acids ◽  
Esophageal Adenocarcinoma ◽  
Cell Lines ◽  
Chronic Exposure ◽  
Squamous Epithelium ◽  
Deoxycholic Acid ◽  
Beclin 1 ◽  
Rat Tissues ◽  
Increased Risk

Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance.

A systematic review: The role of gender in staffs’ experience of working with adult survivors of sexual trauma

2021 ◽  
Vol 2 (2) ◽  
pp. 55-68
Author(s):  
Abbey Woodhouse ◽  
◽  
Sarah Craven-Staines ◽  
Keyword(s):  
Systematic Review ◽  
Sexual Trauma ◽  
Adult Survivors ◽  
Critical Examination ◽  
Female Survivors ◽  
Biological Sex ◽  
Client Group ◽  
Increased Risk ◽  
And Gender

Despite the vast amount of research being devoted to the field of sexual abuse and trauma, literature surrounding a gender informed stance is still very much in its infancy. This article presents a systematic review aiming to provide an impartial critical examination of relevant existing literature with the main aim of exploring the role of gender in staffs’ experience of working with survivors of sexual trauma. Electronic databases were searched online. Studies were eligible for inclusion if they investigated the experience and gender of staff working with adult survivors of sexual trauma. The exclusion criteria were studies that focussed on child and adolescent participants, and survivors with an intellectual disability. Eight studies were eligible for inclusion, and as such reviewed by authors; each highlighted the crucial role gender plays in the unique work between professionals and survivors of sexual trauma. Findings from the review highlighted gender as influencing interpersonal dynamics when focussing in on the client and/or the clinician. Clinician gender was felt to be particularly impactful and potentially detrimental should the gender of the professional be the same of that of the client’s historic abuser. Further societal stereotypes and perceptions of what connotes an abuse survivor has implications for working with male and female survivors of sexual trauma. As a result, there is potential for males being discouraged from making disclosures due to a subconscious reduced openness to males as survivors, rather than abusers. Increased empathy was found more often to be afforded to female survivors, with harsher punishments attributed to their abusers. Evidence was also suggested for the global adverse impact of working with this client group on professionals with an increased risk of vicarious traumatisation and burnout highlighted amongst clinicians. Limitations are highlighted in relation to the review’s ability to truly explore gender as the study only made reference to biological sex.

scholarly journals Role of PTPRJ genotype in papillary thyroid carcinoma risk

2010 ◽  
Vol 17 (4) ◽  
pp. 1001-1006 ◽  
Author(s):  
Rodolfo Iuliano ◽  
Dario Palmieri ◽  
Huiling He ◽  
Angela Iervolino ◽  
Eleonora Borbone ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cancer Susceptibility ◽  
Tyrosine Phosphatase ◽  
Susceptibility Gene ◽  
Control Group ◽  
Papillary Thyroid ◽  
Genotype Frequencies ◽  
Increased Risk

The strong genetic predisposition to papillary thyroid carcinoma (PTC) might be due to a combination of low-penetrance susceptibility variants. Thus, the research into gene variants involved in the increase of susceptibility to PTC is a relevant field of investigation. The gene coding for the receptor-type tyrosine phosphatase PTPRJ has been proposed as a cancer susceptibility gene, and its role as a tumor suppressor gene is well established in thyroid carcinogenesis. In this study, we want to ascertain the role of PTPRJ genotype in the risk for PTC. We performed a case–control study in which we determined the PTPRJ genotype for the non-synonymous Gln276Pro and Asp872Glu polymorphisms by PCR amplification and sequencing. We calculated allele and genotype frequencies for the considered polymorphisms of PTPRJ in a total sample of 299 cases (PTC patients) and 339 controls (healthy subjects) selected from Caucasian populations. We observed a significantly higher frequency of homozygotes for the Asp872 allele in the group of PTC patients than in the control group (odds ratio=1.61, 95% confidence interval 1.15–2.25, P=0.0053). We observed a non-significant increased frequency of homozygotes for Gln276Pro polymorphism in PTC cases in two distinct Caucasian populations. Therefore, the results reported here show that the homozygous genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC.

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