Joana Bastos

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours

IntroductionThe expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERα, both encoding for transcription factors with a potential involvement in the ERα-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERα-negative/poor prognosis breast cancer group.MethodsWe evaluate FOXA1 and GATA-3 expression in 249 breast carcinomas by immunohistochemistry, associating it with breast cancer molecular markers, clinicopathological features and patients survival. The clinicopathological features and immunohistochemical markers of the tumours were compared using the chi-square test and ANOVA. Disease-free survival was analysed through Kaplan–Meier survival curves and Cox regression.ResultsFOXA1 expression was demonstrated in 42% of invasive carcinomas, while GATA-3 was detected in 48% of the cases. FOXA1 expression was inversely associated with tumour size, Nottingham Prognostic Index, histological grade, lymph vascular invasion, lymph node stage and human epidermal growth factor receptor-2 (HER-2) overexpression, while GATA-3 expression showed inverse association with histological grade and HER-2. Both FOXA1 and GATA-3 were directly associated with ERα and progesterone receptor. Among FOXA1-positive tumours, 83.1% are comprised in the luminal A subtype, similar to GATA-3 where 87.7% of positive tumours were classified within this molecular subtype. In the subset of ERα-negative patients, those who were FOXA1-negative had a 3.61-fold increased risk of breast cancer recurrence when compared with the FOXA1-positive.ConclusionsFOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERα-negative patients.

The state of the art of cancer control in 30 European countries in 2008

Inequalities in cancer incidence, mortality and survival represent a major challenge for public health. Addressing this challenge requires complex and multidisciplinary approaches. Sharing successful experiences from across Europe may therefore be of benefit. We describe the state of the art of cancer control structures in the 27 European Union countries, plus Iceland, Norway and Switzerland, at the beginning of 2008. Information on cancer plans, cancer registries, cancer screening, Human Papillomavirus (HPV) vaccination and smoking restrictions in each country was identified through PubMed, the official websites of national and international organizations and Google™ searches. Experts and/or health authorities from each country completed and validated the information. Sixteen countries had implemented national cancer plans in 2008. Twenty four countries had population‐based cancer registries with 100% coverage. The exceptions were Greece and Luxembourg (no population‐based registry yet), France, Italy and Spain (<50%), and Switzerland (62%). In 9 countries, population coverage of breast cancer screening was 100% with participation ranging from 26 to 87%; 8 countries did not have organized programmes. Seven countries had cervical cancer screening programmes with 100% coverage with participation ranging from 10 to 80%; 8 countries had no organized programme. Nine countries had announced national HPV vaccination policies by early 2008. Six countries had organized colorectal cancer screening programmes. Five countries had complete bans on smoking in public places. There is wide international heterogeneity in cancer control structures in Europe. This provides considerable scope and motivation for cooperation and sharing of experience.

Sociodemographic Determinants of Prevalence and Incidence of Helicobacter pylori Infection in Portuguese Adults

Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori‐related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal.

Prevalence, incidence and risk factors for Helicobacter pylori infection in a cohort of Portuguese adolescents (EpiTeen)

BACKGROUND Helicobacter pylori infection is acquired mainly during childhood, but it may occur throughout life. Understanding the determinants of infection at different ages is essential to clarify dynamics of H. pylori related diseases and to design preventive strategies. AIM To estimate the prevalence of H. pylori infection at the age of 13 and the incidence after a 3-year follow-up and to identify risk factors for infection. SUBJECTS AND METHODS Adolescents born in 1990 were recruited in schools from Porto. Whole-cell anti-H. pylori IgG antibodies were quantified by ELISA. Prevalence ratios (PR) and incidence rate ratios (RR) adjusted for parental education were computed at baseline (n = 1312) and at follow-up (n = 280). RESULTS The prevalence was 66.2%, lower in subjects with more educated parents (PR = 0.72, 95%CI: 0.63-0.82), and higher for those having more than one sibling (PR = 1.10, 95%CI: 1.02-1.19) and for smokers (PR = 1.11, 95%CI: 1.02-1.20). The incidence was 4.1/100 person-years. Smoking (RR = 2.35, 95%CI: 1.16-4.75) and type of school (RR = 0.38, 95%CI: 0.16-0.95) were associated with the incidence of infection. CONCLUSIONS Prevalence and incidence of H. pylori infection were high, suggesting that gastric cancer will remain an important public health problem in this generation of Portuguese. We identified smoking as a modifiable risk factor for infection.

Dietary patterns and gastric cancer in a Portuguese urban population

Dietary patterns analysis is a powerful technique to study the relations between diet and cancer. We aimed to quantify the association between dietary patterns and gastric cancer, by location and histological type, according to Helicobacter pylori infection status. We analyzed 591 incident cases of gastric adenocarcinoma and 1,463 community controls. Dietary intake was assessed using a validated food frequency questionnaire. Principal components and cluster analyses were used to define dietary patterns. Anti‐H. pylori IgG was assessed by ELISA. Age‐, gender‐, education‐ and total energy intake‐adjusted odds ratios (OR) were computed. Three dietary patterns were identified, with the following main characteristics: (I) high consumption of fruits and dairy products, and low consumption of alcoholic beverages; (II) low consumption of fruit, salads, vegetables, dairy products, fish and meat; (III) high consumptions of most food groups and low vegetable soup intake. Compared to pattern I, the risk of gastric cancer was higher for pattern II (OR = 1.68, 95% CI: 1.31–2.14) but not for pattern III (OR = 0.80, 95% CI: 0.57–1.14), with no effect modification by H. pylori infection. The association was similar for cardia and non‐cardia gastric cancer, but for tumors of the diffuse Laurén histological type, the association was weaker for pattern II vs. I (OR = 1.32, 95% CI: 0.83–2.08) and a protective effect was observed for pattern III vs. I (OR = 0.43, 95% CI: 0.22–0.87). Our results confirm the protective effect of high fruit and vegetables intake, and show a differential association according to histological type. No effect modification by H. pylori infection was observed.

Dietary patterns and colorectal cancer: a case-control study from Portugal.

Dietary pattern analysis is a powerful technique to study the relationships between diet and cancer, accounting for the specificities of overall dietary intake in each setting. The objective of this study was to quantify the association between dietary patterns and colon and rectum cancers. We evaluated 151 rectum and 102 colon cancer cases selected among surgical patients at the Portuguese Oncology Institute, and 879 community controls. Dietary intake was assessed using a validated food frequency questionnaire. Dietary patterns were defined with principal components and cluster analyses. Age, sex, education, total energy intake, and physical activity-adjusted odds ratios (OR) and 95% confidence intervals (95% CIs) were computed. Three dietary patterns were identified: (i) PI: ‘healthy,’ high consumption of dairy products, wholegrain cereals, vegetables/salads, legumes, fruits and vegetable soup, and low intake of wine; (ii) PII: ‘low consumption of milk and foods containing dietary fiber,’ low intake of dairy products, vegetables/salads, legumes, and fruits; and (iii) PIII: ‘western,’ high consumption of red/processed meat, refined cereals, sugar and sweets, potatoes, alcoholic beverages, and low intake of wholegrain cereals and vegetable soup. Compared with PI, the risk of colon cancer was higher among subjects with PII (OR=2.07; 95% CI: 1.04–4.14) and PIII (OR=2.35; 95% CI: 1.19–4.64). The OR estimates for rectum cancer were 3.12 (95% CI: 1.74–5.61) and 1.41 (95% CI: 0.75–2.63), respectively. Our results confirm the higher risk of colorectal cancer among subjects with ‘western’ diets and ‘low consumption of milk and foods containing foods containing dietary fiber’. At a local level, these results support public health messages based on the accumulated evidence on the relationship between individual food items/groups and colorectal cancer.

Childcare attendance and Helicobacter pylori infection: systematic review and meta-analysis.

Helicobacter pylori infection is acquired predominantly during childhood. Childcare promotes interpersonal contact and may be an important determinant of infection. The aim was to quantify the association between childcare attendance and H. pylori infection in childhood or adolescence. PubMed was searched up to July 2012 to identify eligible studies. The DerSimonian and Laird method was used to compute summary odds ratio (OR) estimates and 95% confidence intervals (CIs); heterogeneity was quantified with the I2 statistic and explained through stratified analyses and metaregression. Sixteen studies compared participants attending childcare with those not exposed. The summary OR was 1.12 (95% CI: 0.82–1.52, I2=77.4%). Summary estimates were similar for crude and adjusted estimates, and higher when the infection was evaluated in children of 3 years or younger (OR=2.00, 95% CI: 0.94–4.29, I2=55.0%). Studies based on the detection of stool antigens yielded higher estimates (OR=2.65, 95% CI: 1.24–5.66, I2=36.4%). Those conducted in settings with a high prevalence of H. pylori infection yielded stronger associations (OR=1.44, 95% CI: 0.94–2.20, I2=74.3%). In multivariate metaregression, there was no significant association with any of these variables; taking them into account contributed to a reduction of I2 to 67%. The role of childcare as a risk factor for H. pylori infection is confirmed by our results, especially in settings with a high prevalence of infection. However, the association was moderate, and the effect of the type of childcare setting or the duration or the intensity of exposure was seldom addressed, leaving considerable scope for improving our understanding of how this modifiable exposure contributes towards H. pylori infection.

Helicobacter pylori cag pathogenicity island-positive strains induce syndecan-4 expression in gastric epithelial cells.

Helicobacter pylori is recognized as the main cause of gastritis and is associated with gastric carcinogenesis. Syndecan-4 represents the major source of heparan sulfate (HS) in the gastric cells. HS proteoglycans expressed on the cell surface constitute targets for H. pylori at the early stage of infection. The aim of this study was to determine whether H. pylori induction of syndecan-4 expression is affected by the virulence characteristics of the infecting strain, namely the cytotoxic-associated gene (cag) pathogenicity island (PAI). We observed that individuals infected with highly pathogenic H. pylori strains express syndecan-4 in the foveolar epithelium of the gastric mucosa. The association between the cagPAI status of the infecting strain and syndecan-4 expression was further demonstrated by infection of gastric epithelial cell lines with a panel of cagPAI(+) and cagPAI(-)H. pylori strains, showing that expression of syndecan-4 was significantly increased in response to infection with the highly pathogenic strains. Moreover, infection of gastric cells with cagA and cagE mutant strains further confirmed that syndecan-4 induction is dependent on an intact cagPAI. The present study shows that highly pathogenic H. pylori strains induce syndecan-4 expression, both in human gastric mucosa and in gastric cell lines, in a cagPAI-dependent manner.

Child day-care attendance and Helicobacter pylori infection in the Portuguese birth cohort Geração XXI.

Helicobacter pylori infection is the most important risk factor for gastric cancer. It is acquired predominantly during childhood, and understanding the determinants of infection in early life may translate into identifying preventive measures. However, the independent role of child day-care attendance remains to be understood. The aim of the study was to evaluate the association between child day-care attendance and H. pylori infection in early life. The study was nested within Geração XXI, a birth cohort assembled in Portugal. Serum anti-H. pylori IgG was quantified using ELISA in 1047 children between the ages of 4 and 5 years, and information on child day-care attendance since birth was collected. Odds ratios and 95% confidence intervals (95% CIs), adjusted for the child’s age and number of siblings, as well as maternal education and infection status, were computed using unconditional logistic regression. The prevalence of H. pylori infection was 30.6% (95% CI 27.9–33.6), and it increased significantly with the cumulative time of attendance in day-care centers/homes (from 13.2% among never attendees to 40.2% among those attending for >36 months; P for trend<0.001). The odds ratio was 4.88 (95% CI 2.55–9.35) among those attending these institutions for more than 3 years, in comparison with never attendees. H. pylori infection remains a frequent and early event in Portugal. Child day-care attendance increases the risk of infection, making this setting a target for preventive measures.

Evolução da mortalidade por cancro do pulmão em Portugal (1955-2005)

Introduction: While the rate of smoking and lung cancer mortality has been decreasing in western Europe, there was no decline in lung cancer mortality in Portugal until 1998. Aim: To describe lung cancer mortality trends in Portugal. Methods: Lung cancer mortality rates (International Disease Classification 10: C33-34) in Portugal 1955-2005 by gender and 5-year age groupings were provided by the World Health Organization and the National Institute of Statistics. Standard mortality rates (direct method, world population) were calculated for the 35-74, 35-44, 45-54, 55-64 and 65-74 year-old age groups. Joinpoint regression was used to calculate the annual percent change (APC) in mortality and to identify any inflection points. Results: Between 1955 and 2005 we observed a stabilisation in lung cancer mortality in men aged 35-74 years old, varying 3.77%/year (95% confidence interval [95%CI]: 3.53-4.01) in 1955-1986 and -0.15%/year (95%CI: -0.99-0.69) in 1996-2005. We observed negative APC point estimates (with none significantly below zero) in the most recent trends except for the 45-54 age group, where we only noted an APC deceleration since 1981. The mortality increased 1.60%/year (95%CI: 1.40-1.77) in women aged 35-74 years old 1955-2005. Conclusion: In the last two decades we observed a lung cancer mortality stabilisation in males, whereas mortality in females increased continuously. These results place Portugal at the end of the third stage of the smoking epidemic. Rev Port Pneumol 2009; XV (4): 575-587