A Systematic Review of Meta-Analyses on Gene Polymorphisms and Gastric Cancer Risk

BACKGROUND: Individual variations in gastric cancer risk have been associated in the last decade with specific variant alleles of different genes that are present in a significant proportion of the population. Polymorphisms may modify the effects of environmental exposures, and these gene-environment interactions could partly explain the high variation of gastric cancer incidence around the world. The aim of this report is to carry out a systematic review of the published meta-analyses of studies investigating the association between gene polymorphisms and gastric cancer risk, and describe their impact at population level. Priorities on the design of further primary studies are then provided. METHODS: A structured bibliographic search on Medline and EMBASE databases has been performed to identify meta-analyses on genetic susceptibility to gastric cancer, without restriction criteria. We report the main results of the meta-analyses and we describe the subgroup analyses performed, focusing on the detection of statistical heterogeneity. We investigated publication bias by pooling the primary studies included in the meta-analyses, and we computed the population attributable risk (PAR) for each polymorphism. RESULTS: Twelve meta-analyses and one pooled-analysis of community based genetic association studies were included, focusing on nine genes involved in inflammation (IL-1beta, IL-1RN, IL-8), detoxification of carcinogens (GSTs, CYP2E1), folate metabolism (MTHFR), intercellular adhesion (E-cadherin) and cell cycle regulation (p53). According to their random-Odds Ratios, individuals carrying one of the IL-1RN *2, IL-1beta -511T variant alleles or homozygotes for MTHFR 677T are significantly at higher risk of gastric cancer than those with the wild type homozygote genotypes, showing high PARs. The main sources of heterogeneity in the meta-analyses were ethnicity, quality of the primary study, and selected environmental co-exposures. Effect modification by Helicobacter pylori infection for subjects carrying the unfavourable variant of IL-1 polymorphisms and by low folate intake for individuals homozygotes for MTHFR 677T allele has been reported, while genes involved in the detoxification of carcinogens show synergistic interactions. Publication bias was observed (Egger test, p = 0.03). DISCUSSION: The published meta-analyses included in our systematic review focused on polymorphisms having a small effect in increasing gastric cancer risk per se. Nevertheless, the risk increase by interacting with environmental exposures and in combination with additional unfavourable polymorphisms. Unfortunately meta-analyses are underpowered for many subgroup analyses, so additional primary studies performed on larger population and collecting data on environmental and genetic co-exposures are demanded

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to analyze the combined effects of selected <it>p</it>53 and <it>p</it>73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.</p> <p>Methods</p> <p>Two hundred and eighty-three cases and 295 hospital controls were genotyped for <it>p</it>53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and <it>p</it>73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the <it>p</it>53 polymorphisms, and a gene-gene interaction analysis for the combined effects of <it>p</it>73 G4C14-to-A4T14 and <it>p</it>53 polymorphisms.</p> <p>Results</p> <p>We found a significant increased risk of SCCHN among individuals with combined <it>p</it>73 exon 2 G4A and <it>p</it>53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the <it>p</it>53 exon 4-<it>p</it>53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying <it>p</it>73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among <it>p</it>53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).</p> <p>Conclusion</p> <p>Our study provides for the first time evidence that individuals carrying <it>p</it>53 exon 4 and <it>p</it>53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of <it>p</it>73 exon 2 G4C14-to-A4T14 and <it>p</it>53 intron 3 variant allele. Larger studies are required to confirm these findings.</p

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

A large cross-sectional survey investigating the knowledge of cervical cancer risk aetiology and the predictors of the adherence to cervical cancer screening related to mass media campaign

Objectives. The aims of this study were to compare the characteristics of women who got a Pap-test during the mass media campaign, carried out in an Italian region by broadcasts advertising, and two years later and to identify the determinants of knowledge of cervical cancer etiology and of the adherence to the mass media campaign. Methods. A cross-sectional survey was carried out through a self-administered questionnaire. Results. A total of 8570 randomly selected women were surveyed, 823 of these had a Pap-test during the mass media campaign period and 7747 two years later. Higher educational level, being not married, and living in urban areas were the main independent characteristics associated with a higher level of knowledge of cervical cancer etiology, although a previous treatment following a Pap smear abnormality was the strongest predictor (OR = 2.88; 95% CI: 2.43-3.41). During the campaign period women had the Pap-test more frequently as a consequence of the mass media campaign (OR = 8.28; 95% CI; 5.51-12.45). Conclusions. Mass media campaign is a useful tool to foster cervical screening compliance; however, its short-term effect suggests repeating it regularly. © 2014 Corrado De Vito et al

A Large Cross-Sectional Survey Investigating the Knowledge of Cervical Cancer Risk Aetiology and the Predictors of the Adherence to Cervical Cancer Screening Related to Mass Media Campaign

Objectives. The aims of this study were to compare the characteristics of women who got a Pap-test during the mass media campaign, carried out in an Italian region by broadcasts advertising, and two years later and to identify the determinants of knowledge of cervical cancer etiology and of the adherence to the mass media campaign. Methods. A cross-sectional survey was carried out through a self-administered questionnaire. Results. A total of 8570 randomly selected women were surveyed, 823 of these had a Pap-test during the mass media campaign period and 7747 two years later. Higher educational level, being not married, and living in urban areas were the main independent characteristics associated with a higher level of knowledge of cervical cancer etiology, although a previous treatment following a Pap smear abnormality was the strongest predictor (OR = 2.88; 95% CI: 2.43–3.41). During the campaign period women had the Pap-test more frequently as a consequence of the mass media campaign (OR = 8.28; 95% CI; 5.51–12.45). Conclusions. Mass media campaign is a useful tool to foster cervical screening compliance; however, its short-term effect suggests repeating it regularly

Patient-centredness and e-Health among the Italian Hospitals: results of a cross-sectional web-based survey

OBJECTIVES: Given the growing recognition of patient-centeredness as a healthcare quality indicator and its limited implementation in practice, our study evaluated how the Italian hospitals (ItHs), including research hospitals (IRCCSs), research teaching hospitals (THs), and independent public hospital trusts (AOs), address the dimension of online data access through their institutional Web sites to promote a patient-centered care. MATERIALS AND METHODS: To address patient-centeredness and e-health, eight specific indicators adapted from the Euro Health Consumer Index were evaluated from 169 ItHs: online booking of healthcare services; access to medical records; register of legitimate doctors; waiting times for most commonly delivered healthcare services; transport information; centralized booking; public relations office; and pain management hospital committee. Univariate and bivariate statistics and a logistic regression analysis have been performed. RESULTS: The majority of the ItHs were under public ownership, and half of them are located in Northern Italy. From the logistic regression analysis, AOs appeared to be more likely to develop a patient-centered healthcare approach (odds ratio [OR]=3.69; 95% confidence interval [CI] 1.14-11.89) compared with IRCCSs or THs. In addition, when grouped together, all public hospitals show more than threefold higher implementation of patient-centeredness strategies (OR=3.60; 95% CI 1.49-8.72) with respect to private ones. Northern hospitals are more likely to ensure wider implementation of a patient-centered approach to healthcare (OR=3.37; 95% CI 1.49-7.62). CONCLUSIONS: According to our results, most of the ItHs are under public ownership, and half of them are located in the northern regions of Italy. The higher implementation of patient-centeredness strategies observed for Northern hospitals highlights interregional disparity in healthcare that needs a coordinated effort at both the hospital and policymaker levels to ensure a widespread implementation of patient-centered care among all Italian regions