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Background Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. Methods We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. Results At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58–52 (r = 0.86), 58–33 (r = 0.75), 33–52 (r = 0.72), and between GST-E6: 52–11 (r = 0.84), 52–18 (r = 0.79), 58–33 (r = 0.78), 35–11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%–62.2%). Conclusions Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.

PURPOSE: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. METHODS: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). RESULTS: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. CONCLUSION: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

A tuberculose é uma doença bacteriana que se tornou um grande problema de Saúde Pública no Brasil. O presente artigo buscou relatar a história das políticas públicas adotadas para o controle da tuberculose, as taxas de incidência da doença, as características do agente etiológico, o processo de infecção e adoecimento e as formas clínicas da patologia. Além disso, dados do Departamento de Informática do Sistema Único de Saúde foram relatados. Foram utilizadas fontes de pesquisa primárias e secundárias para obtenção do referencial teórico para produção deste artigo. Com base na revisão sistemática da literatura realizada, conclui-se que é necessário a adoção de medidas efetivas para a diminuição da incidência e do número de óbitos causados pela tuberculose no Brasil.

Background: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). Methods: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. Results: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94–1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88–0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85–0.99) and 0.78 (95% CI = 0.73–0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91–1.02) for cardia, 1.03 (95% CI = 1.00–1.07) for non-cardia, 1.12 (95% CI = 1.07–1.19) for diffuse and 1.02 (95% CI = 0.97–1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. Conclusions: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association., Fondazione AIRC per la ricerca sul cancro 21378, Unidade de Investigacao em Epidemiologia-Instituto de Saude Publica da Universidade do Porto (EPIUnit) UIDB/04750/2020, National funds from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education), Project NEON-PC-Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline' - FEDER through the Operational Program Competitiveness and Internationalisation POCI-01-0145-FEDER-03235 PTDC/SAU-EPI/32358/2017, Fundacao para a Ciencia e a Tecnologia (FCT), EPIunit-Junior Research-Prog Financing UIDP/04750/2020, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 2014/26897-0, European Cancer Prevention Organization, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI)

Background: The prevalence of Helicobacter pylori–negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. Methods: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). Results: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03–4.61] and were current smokers (OR = 2.16; 95% CI, 0.52–9.02). Conclusion: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. Impact: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

IntroductionIncome, a component of socioeconomic status, influences cancer risk as a social determinant of health. We evaluated the independent associations between individual- and area-level income, and site-specific cancer incidence in Canada.MethodsWe used data from the 2006 and 2011 Canadian Census Health and Environment Cohorts, which are probabilistically linked datasets constituted by 5.9 million and 6.5 million respondents of the 2006 Canadian long-form census and 2011 National Household Survey, respectively. Individuals were linked to the Canadian Cancer Registry through 2015. Individual-level income was derived using after-tax household income adjusted for household size. Annual tax return postal codes were used to assign area-level household income quintiles to individuals for each year of follow-up. We calculated age-standardized incidence rates (ASIR) and rate ratios for cancers overall and by site. We conducted multivariable negative binomial regression to adjust these rates for other demographic and socioeconomic variables.ResultsIndividuals of lower individual- and area-level income had higher ASIRs compared to those in the wealthiest income quintile for head and neck, oropharyngeal, esophageal, stomach, colorectal, anal, liver, pancreas, lung, cervical, and kidney and renal pelvis cancers. Conversely, individuals of wealthier individual- and area-level income had higher ASIRs for melanoma, leukemia, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma, breast, uterine, prostate, and testicular cancers. Most differences in site-specific incidence by income quintile remained after adjustment.ConclusionsAlthough Canada’s publicly funded healthcare system provides universal coverage, inequalities in cancer incidence persist across individual- and area-level income gradients. Our estimates suggest that individual- and area-level income affect cancer incidence through independent mechanisms.

Background: The Canadian Cancer Registry (CCR) does not collect demographic data beyond age and sex, making it difficult to monitor health inequalities. Using data linkage, we compared site-specific cancer incidence rates by race. Methods: The 2006 and 2011 Canadian Census Health and Environment Cohorts are population-based probabilistically linked datasets of 5.9 million respondents of the 2006 long-form census and 6.5 million respondents of the 2011 National Household Survey. Race was self-reported. Respondent data were linked with the CCR up to 2015. We calculated age-standardized incidence rate ratios (ASIRR), comparing group-specific rates to the overall population rate with bootstrapped 95% confidence intervals (CI). We used negative binomial regressions to adjust for socioeconomic variables and assess interactions with immigration status. Results: The age-standardized overall cancer incidence rate was lower in almost all non-White racial groups than in the overall population, except for White and Indigenous peoples who had higher incidence rates than the overall population (ASIRRs, 1.03–1.04). Immigrants had substantially lower age-standardized overall cancer incidence rates than nonimmigrants (ASIRR, 0.83; 95% CI, 0.82–0.84). Stomach, liver, and thyroid cancers and multiple myelomas were the sites where non-White racial groups had consistently higher site-specific cancer incidence rates than the overall population. Immigration status was an important modifier of cancer risk in the interaction model. Conclusions: Differences in cancer incidence between racial groups are likely influenced by differences in lifestyles, early life exposures, and selection factors for immigration. Impact: Data linkage can help monitor health inequalities and assess progress in preventive interventions against cancer.

Purpose To identify trajectories of cognitive performance up to five years since diagnosis and their predictors, in a cohort of patients with breast cancer (BCa). Methods A total of 464 women with BCa admitted to the Portuguese Institute of Oncology, Porto, during 2012, were evaluated with the Montreal Cognitive Assessment (MoCA) before any treatment, and after one, three and five years. Probable cognitive impairment (PCI) at baseline was defined based on normative age- and education-specific reference values. Mclust was used to define MoCA trajectories. Receiver Operating Characteristic curves were used to assess the predictive accuracy for cognitive trajectories. Results Two trajectories were identified, one with higher scores and increasing overtime, and the other, including 25.9% of the participants, showing a continuous decline. To further characterize each trajectory, participants were also classified as scoring above or below the median baseline MoCA scores. This resulted in four groups: 1) highest baseline scores, stable overtime (0.0% with PCI); 2) lowest baseline scores (29.5% with PCI); 3) mid-range scores at baseline, increasing overtime (10.5% with PCI); 4) mid-range scores at baseline, decreasing overtime (0.0% with PCI). Adding the change in MoCA during the first year to baseline variables significantly increased the accuracy to predict the downward trajectory (area under the curve [AUC] = 0.732 vs. AUC = 0.841, P, Highlights • 5-year cognitive trajectories since diagnosis of breast cancer were identified. • 25.9% of breast cancer survivors had a declining cognitive trajectory. • Cognitive performance during the 1st year predicted the 5-year trajectory.

Prostate cancer (PCa) is the most prevalent among men, and psychological symptoms may affect many patients. This study aims to describe the prevalence of probable anxiety and depression before PCa treatments and after one year and to identify sociodemographic and clinical factors associated with these outcomes. Between February 2018 and March 2020, 292 patients recently diagnosed with PCa were recruited at the Instituto Português de Oncologia—Porto. The Hospital Anxiety and Depression Scale (HADS) was used to define probable anxiety and depression (cutoff = 11). The prevalence of probable anxiety remained stable from baseline to one year (7.8% vs. 8.5%, p = 0.866) while there was an increase in probable depression (3.1% vs. 6.8%, p = 0.012). After one year, probable depression persisted in 55.6% of patients with probable depression at baseline and 47.8% of those with probable anxiety at the first assessment had normal anxiety scores. At baseline, anxiety was more frequent among dwellers in rural areas (adjusted odds ratio—aOR, 95%CI: 2.80, 0.91–8.58) and less frequent in patients with body mass index 25–29.9 kg/m2 (aOR, 95%CI: 0.33, 0.12–0.91) compared to 18.5–24.9 Kg/m2, while those living alone had higher odds of depression (aOR, 95%CI: 6.35, 1.43–28.30). The frequency of anxiety and depression fluctuated during the course of treatment. Monitoring these symptoms would identify the most affected patients, contributing for a better use of mental health services., This study was funded by the European Regional Development Fund through the Operational Program Competitiveness and Internationalization, and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project “NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit, UIDB/04750/2020; ITR, LA/P/0064/2020) financed by national funds from FCT. AC, CL, and SM were funded under the scope of the project “NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). SM also received funding under EPIUnit—Junior Research—Prog Financing (UIDP/04750/2020). An individual PhD grant attributed to NA (SFRH/BD/119390/2016) was funded by FCT and the “Programa Operacional Capital Humano” (POCH/FSE).

Females and males frequently report substantial differences in social capital indicators and may use healthcare distinctly. Nevertheless, the potential effect of sex on the relation between social capital and healthcare use remains unclear. This study aims to quantify the association between different indicators of individuals' social capital and healthcare use, according to sex. Data were retrieved from the Sixth Wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), which was conducted in 2015, and included 68,188 participants from 18 countries. Adjusted odds ratios (AOR) and 95% confidence intervals (95%CI) were computed using logistic regression. Overall, males and females with smaller social networks, those who live alone or with any other relatives besides their partners, and those whose first close confidant was a family member or a neighbour reported fewer contacts with medical doctors or nurses, as well as with dentists or dental hygienists. Amongst females, participation in educational or training courses (AOR = 1.67, 95%CI:1.40-2.00; p for interaction = 0.035) and sport, social or any other club (AOR = 1.79, 95%CI:1.58-2.02; p for interaction = 0.043) was associated with a more frequent contact with dentists or dental hygienists. Females who participated in volunteer or charity work (AOR = 0.76, 95%CI:0.64-0.91; p for interaction = 0.042) and political or community-related organisations (AOR = 0.72, 95%CI:0.52-1.00; p for interaction = 0.030) were less likely to report the use of polypharmacy. This outcome was more frequently observed amongst females who referred feelings of severe loneliness (AOR = 1.44, 95%CI:1.22-1.68; p for interaction0.001). Social capital is associated with healthcare use distinctively amongst males and females. Increasing opportunities for social participation may improve healthcare use, particularly amongst females.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83–0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77–0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81–0.94), and for diffuse (OR = 0.79, 95% CI = 0.69–0.89) and intestinal type (OR = 0.88, 95% CI = 0.79–0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis.

Breast cancer incidence is rising in low-income countries, but there is limited information regarding health resource allocation for its care. We assessed the cost of care during the first three years after diagnosis in a low-income country (Mozambique; n = 162 women) and compared it with a high-income country (Portugal, n = 703 women). Local currency prices were converted to 2019 international dollars (Int$). In Mozambique, the median cost was lower than in Portugal (2888 vs 18,533 Int$, respectively) and did not vary across stage or tumor subtype. These findings may help improving resource allocation for breast cancer care in Sub-Saharan Africa, despite reflecting an underfunding of treatment in this setting., Highlights • Health resource allocation for breast cancer care is ill-defined in low-income countries. • The median cost of care of non-metastatic breast cancer was 6-fold higher in Portugal vs Mozambique. • The median cost of care did not vary across stage or tumor subtype in Mozambique. • These findings reflect an underfunding of breast cancer treatment in this low-income setting. • These data may help improving resource allocation for breast cancer care in Sub-Saharan Africa.

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer., The authors thank the European Cancer Prevention (ECP) Organiza- tion for providing support for the project meetings. Our study is supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB) and the Italian League for the Fight against Cancer (LILT). This project was also supported by FEDER through the Operational Programme Competi- tiveness and Internationalization and national funding from the Foun- dation for Science and Technology - FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigaç ~ ao em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020). AF (PD/BD/ 105823/2014) was awarded with an individual scholarship through national funding from FCT/MCTES. Individual grants attributed to ARC (SFRH/BD/102181/2014) and BP (SFRH/BPD/108751/2015) were funded by the FCT and the “ Programa Operacional Capital Humano ” (POCH/FSE). SM was funded under the project “ NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline “ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). We also thank all MCC-Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, University of León, Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and collaborators). The funding source had no role in the study design; collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

The association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC.Data from three studies of the StoP Project with available information on metformin intake were analyzed. Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model. The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials.The OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants' characteristics or when restricting the analyses to those with a history of diabetes. The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake.The results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I(2) > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

Background: \ud Helicobacter pylori is the most important risk factor for non-cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status.\ud \ud Methods: \ud A pooled analysis of individual-level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti-Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two-stage approach was used to pool study-specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta-analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted.\ud \ud Results: \ud The OR for the association between serology-defined H. pylori and NCGC was 1.45 (95% CI: 0.87–2.42), which increased to 4.79 (95% CI: 2.39–9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region—a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22–4.07) for ELISA or EIA and 9.22 (95% CI: 3.12–27.21) for immunoblot or multiplex serology.\ud \ud Conclusion: \ud The NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

Introduction: The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa. Methods: Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. Results: Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47–0.90%) and among SPCs, 7.21% (4.99–9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61–5.07). Discussion/Conclusion: The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.

Background/Objective Androgen deprivation therapy (ADT) has been associated with cognitive decline, but results have been heterogenous. We describe changes in cognitive performance in patients with prostate cancer (PCa), according to treatment with ADT, during the 1st year after PCa diagnosis. Methods Between February 2018 and March 2021, 348 patients with PCa treated at the Instituto Português de Oncologia do Porto were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after one year (1y). ADT was used in 183 participants, and 165 were treated without ADT (total prostatectomy, radiotherapy, brachytherapy, active surveillance). Cognitive decline was defined as the decrease in MoCA from baseline to the 1y-evaluation below 1.5SD of the distribution of the MoCA variation in the whole cohort. Participants scoring below age- and education-based normative reference values in MoCA were considered to have probable cognitive impairment (PCI). Multivariate logistic regression was used to estimate age- and education-adjusted OR (aOR) of the association between ADT and cognitive decline/incident PCI. Results/Discussion PCI was observed in 12.4% of the patients at baseline. Mean MoCA scores increased from baseline to the 1y-evaluation (22.4 vs. 22.9, p = 0.001), and 51.2% of PCI cases at baseline had normal MoCA scores at 1y. Cognitive decline was most frequent in the ADT group (9.3% vs. 3.6%, p = 0.034), although the aOR was 2.44 (95%CI:0.89-6.71). The 1yr cumulative incidence of PCI was 10.4% (95%CI:6.2%-16.2%) in the ADT-group and 2.8% (95%CI:0.8-%-7.1%) in the non-ADT group [aOR=3.15 (95%CI:0.97-10.25)]. Conclusions ADT was associated with a decrease in the cognitive performance of PCa patients during the 1st year after diagnosis. The completion of the 1y-evaluation in the whole cohort (n = 600) is needed to confirm these preliminary results. Funding POCI-01-0145FEDER-032358;PTDC/SAU-EPI/32358/2017; UIDB/4750/2020;SFRH/BD/119390/2016 Key messages Half of the cases with cognitive impairment at baseline improved at one-year. Patients treated with ADT seem to be affected by cognitive decline more frequently.

Background/Objective Up to 30% of patients with cancer may present cognitive impairment (CI) before treatment but data are scarce regarding prostate cancer (PCa). We aim to estimate the prevalence of CI in patients with PCa, before cancer treatment. Methods Between February 2018 and April 2021, the NEON-PC cohort included 609 patients with a recent PCa diagnosis to be treated at Instituto Português de Oncologia do Porto. Previous history of chemotherapy, radiotherapy, androgen deprivation therapy, and neurologic or psychyatric conditions impairing cognitive performance were exclusion criteria. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance before any treatment for PCa. Participants with a MoCA at least 1.5 SD below age- and education-specific norms were considered to have probable cognitive impairment (PCI) and were proposed for a comprehensive neuropsychological (NP) assessment. Participants scoring Results/Discussion Prevalence of PCI was 17.4% in the EPIPorto and 15.1% in the NEON-PC cohort (age- and education-adjusted OR = 1.02,95% confidence interval: 0.70,1.50). NP assessment was performed in 65 patients with PCa: 38.5% had normal cognitive function; 7.7% had a light deficit ( Conclusions PCI was as frequent in patients recently diagnosed with PCa as in the general population. Prevalence of CI was lower than in previous reports, which may be explained by differences in the assessment and definition of CI and of the type of cancer. Funding POCI-01-0145FEDER-032358;PTDC/SAU-EPI/32358/2017;UIDB/4750/2020; SFRH/BD/119390/2016 Key messages Patients with prostate cancer and the general population had similar odds of having a score below normative values in the MoCA. Differences in the prevalence of CI between this study and others suggest that the type of cancer may affect patients’ cognitive performance differently, which deserves further confirmation.

Background/Aim: To quantify the association between a previous cancer diagnosis and healthcare use among breast cancer (BC) patients, and estimate five-year recurrence-free survival (RFS). Patients and Methods: Women with BC were classified according to a previous cancer diagnosis (BC or other). Healthcare use during the first year and five-year RFS were obtained through clinical and administrative records. Adjusted odds ratios and hazard ratios (HR) were estimated. Results: Among 681 BC patients, 21 had a previous BC and 32 a previous non-BC. The latter were less likely to receive anthracycline-based combination chemotherapy. The former had higher odds of mastectomy and genetic testing. Five-year RFS HRs (95% confidence interval) were 2.75 (0.79-9.52) and 0.52 (0.07-3.89) for previous BC and non-BC, respectively. Conclusion: Previous cancer was associated with less anthracycline-based combination chemotherapy, and patients were more likely to undergo mastectomy and genetic testing. These findings highlight the need for assessment of previous treatments, personal genetic risk and current BC characteristics. This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education), under the project “A five-year prospective cohort study on the neurological complications of breast cancer: frequency and impact in patient reported outcomes” (POCI-01-0145-FEDER-016867; ref. PTDC/DTP-EPI/7183/2014), and the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; ref. UID/DTP/04750/2019). SM and LC were also funded under the scope of the project "NEON-PC -Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline" (POCI-01-0145-FEDER-032358; ref.PTDC/SAU-EPI/32358/2017). Individual grants attributed to ARC (SFRH/BD/102181/2014) and NA (SFRH/BD/119390/2016) were co-funded by FCT and the Programa Operacional Capital Humano (POCH/FSE). Data management activities up to the first year of follow-up were supported by the Chair on Pain Medicine of the Faculty of Medicine, University of Porto and by the Grünenthal Foundation – Portugal.

Smoking has been associated with acquisition and increased persistence of Helicobacter pylori infection, as well as with lower effectiveness of its eradication. A greater prevalence of infection among smokers could contribute to the increased risk for gastric cancer. We aimed to estimate the association between smoking and seropositivity to H. pylori through an individual participant data pooled analysis using controls from 14 case- control studies participating in the Stomach Cancer Pooling Project. Summary odds ratios and prevalence ratios (PRs), adjusted for age, sex and social class, and the corresponding 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. Heterogeneity was quantified using the I 2 statistic and publication bias with Egger’s test. There was no significant association between smoking (ever vs. never) and H. pylori seropositivity (adjusted odds ratio = 1.08; 95% CI: 0.89 – 1.32; adjusted PR = 1.01; 95% CI: 0.98 – 1.05). The strength of the association did not increase with the intensity or duration of smoking; stratified analyses according to sex, age, region or type of sample did not yield a consistent pattern of variation or statistically significant results, except for participants younger than 55 years and who had been smoking for more than 30 years (adjusted PR = 1.08; 95% CI: 1.02 – 1.15). This is the first collaborative analysis providing pooled estimates for the association between smoking and H. pylori seropositivity, based on detailed and uniform information and adjusting for major covariates. The results do not support an association between smoking and H. pylori infection.

Background Cardiorespiratory fitness is a strong predictor of all-cause morbidity and mortality; nevertheless, the association between cardiorespiratory fitness and the risk of cancer remains unclear. Thus, the aim of this study was to synthetize the evidence on the relationship between cardiorespiratory fitness and the risk of several sites of cancer in men. Methods A computerised search in MEDLINE, EMBASE and Web of Science databases from their inception to 13th February 2019 was performed. Both fixed and random-effects models were used to calculate the pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) to examine the effect of high and moderate versus low cardiorespiratory fitness on site-specific cancer (lung, colon/rectum, prostate) and all-sites cancer. Results Ten studies were included in the qualitative review, and seven of them were included in the meta-analysis. Using low cardiorespiratory fitness as the reference group, moderate and high levels of cardiorespiratory fitness were associated with a lower risk (HRs) of lung cancer, 0.53 (95% confidence interval [CI], 0.39 to 0.68) and 0.52 (95% CI, 0.42 to 0.61); colorectal cancer, 0.74 (95% CI, 0.55 to 0.93) and 0.77 (95% CI, 0.62 to 0.92) and all cancer sites, 0.86 (95% CI, 0.79 to 0.93) and 0.81 (95% CI, 0.75 to 0.87), respectively. Conclusions Among men, cardiorespiratory fitness plays an important role in protecting against the risk of lung and colorectal cancer. Additionally, this protective effect was observed for all-sites cancer risk. These results show the importance of good cardiorespiratory fitness as a potential factor in cancer prevention.

Background Helicobacter pylori (H. pylori) infection is more frequent among men, though the magnitude of the association might be inaccurate due to potential misclassification of lifetime infection and publication bias. Moreover, infection is common, and most studies are cross-sectional. Thus, prevalence ratios (PRs) may be easier to interpret than odds ratios (ORs). Aim The aim of this study was to quantify the association between sex and H. pylori infection using controls from 14 studies from the Stomach Cancer Pooling (StoP) Project. Participants and methods H. pylori infection was defined based on IgG serum antibody titers or multiplex serology. Participants were also classified as infected if gastric atrophy was present, based on histological examination or serum pepsinogen (PG) levels (PG I≤70 and PG I/II ratio≤3). Summary ORs and PRs, adjusted for age, social class and smoking, and corresponding 95% confidence intervals (CIs), were estimated through random-effects meta-analysis. Results Men had significantly higher OR (OR: 1.33, 95% CI: 1.04-1.70) and PR (PR: 1.05, 95% CI: 1.00-1.10) of infection, with stronger associations among hospital-based or older controls. Results were similar when considering the presence of gastric atrophy to define infection status, particularly among participants older than 65 years. Conclusion This collaborative pooled-analysis supports an independent effect of sex on the prevalence of H. pylori infection, while minimizing misclassification of lifetime infection status and publication bias.

Objectives Gastric first primary cancers (FPCs) have an increased risk of developing second primary cancers (SPCs). However, their effect on mortality remains poorly understood. Thus, we aimed to estimate the contribution of SPCs to the mortality of gastric FPCs. Patients and methods A population-based cohort of gastric FPCs diagnosed in 2000-2006 was followed for SPCs (31 December 2012) and vital status (31 December 2017). SPCs (138 synchronous and 205 metachronous, ≤1 and >1 year after the FPC, respectively) were matched (1 : 3, by sex, 5-year age group, and year of FPC diagnosis) with those without an SPC and alive when the corresponding SPC was diagnosed. Results In synchronous SPCs, the hazard ratio (95% confidence interval) for death was 1.07 (0.81-1.40) in males and 0.86 (0.58-1.28) in females; the corresponding estimates for metachronous SPCs were 1.89 (1.49-2.41) and 2.08 (1.42-3.05). In synchronous SPCs, the 10-year cumulative mortality was similar to that of FPCs only; the estimates were higher in lung SPCs. The 10-year cumulative mortality was 75.5% in males and 65.5% in females with metachronous SPCs, which is more than 20% higher than for FPCs only. Conclusion Among patients with gastric FPCs who survive long enough for metachronous SPCs, the latter substantially increases mortality over 10 years, whereas the effect of synchronous SPCs is generally smaller.

Objectives The coronavirus disease 2019 (COVID-19) pandemic has affected the availability of healthcare resources, and adjustments to cancer care have been necessary considering the risk of morbidity by COVID-19 and of cancer progression. This study aims to quantify the impact of the COVID-19 pandemic on the care of patients with cancer by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. Methods Cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, prostate, non-Hodgkin lymphoma, and leukemia from the Portuguese Oncology Institute of Porto, and diagnosed between 2 March and 1 July 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Those with the first treatment outside the Portuguese Oncology Institute of Porto were excluded. Sociodemographic, clinical and treatment characteristics were obtained from the cancer registry database and clinical files. Results The absolute number of new cancer cases decreased nearly 40% after the COVID-19 pandemic (from 1430 to 866). The largest decreases were observed for cervical (-74.3%) and prostate (-71.7%) cancers. Cases were more often diagnosed at more advanced stages in 2020 (P = 0.001), and the proportion of patients not starting any treatment until 1 July was just under 20% in 2019 and nearly 40% in 2020. The median times from symptoms onset, first medical exam and first appointment to diagnosis, and from diagnosis to first appointment, multidisciplinary tumor board meeting and first treatment were shorter after COVID-19. Conclusions There was a notable overall decrease in cancer diagnoses after COVID-19, with changes in the characteristics of incident cases.

PURPOSE The cognitive performance of patients with breast cancer (BCa) may be affected by cancer and its treatments. The Montreal Cognitive Assessment (MoCA) is a widely used cognitive impairment screening tool, but practice effects must be considered for longitudinal assessments. Since learning effects could be overcome through the alternate use of two versions of the MoCA, we aimed to explore their interchangeability by comparing their overall, and domain- and task-specific, scores among patients with BCa. METHODS BCa patients from the NEON-BC cohort were evaluated with the MoCA, version 7.1, after diagnosis and after 1 year. At the 3-year follow-up (n = 422), the 7.1 and 7.3 versions were applied at the beginning and at the end (approximately 1 h later) of this evaluation, respectively. Agreements between versions, regarding total, sub-domain, and task scores, were assessed using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS The mean total scores were not statistically different between versions and the ICC was 0.890. The Bland-Altman limits of agreement were - 3.70 to 3.88. For women with midrange scores, total scores were significantly higher in version 7.1. There were significant differences in the percentage of correct answers in 7 out of 12 tasks, being the highest for the copy of a geometric figure (more than twofold higher with version 7.3). In version 7.1, the language and memory domains presented higher scores and lower visuospatial ability. CONCLUSION Despite similar overall scores being obtained with the two versions of the MoCA, there were item-specific differences that may compromise their interchangeable use.

The prevalence ofCases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data onAmong non-cardia cases, the pooled prevalence of HpNGC was 22.4% (This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives.Our results support that

Introduction: Prostate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline. Methods: Participants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants' cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist. Ethics and dissemination: The study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings. This study was funded by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT) financed by national funds from FCT. SM was funded under the scope of the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Individual PhD grants attributed to ARC (SFRH/BD/102181/2014) and NA (SFRH/BD/119390/2016) were funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE).

Background: Breast cancer incidence is rising in Africa, but there are scare data regarding risk factors in this region. We assessed the relation between risk factors and the occurrence of breast cancer, overall and by tumor subtype in women from Mozambique. Methods: The associations between education, number of births, height, weight, body mass index (BMI), and breast cancer risk among 138 cases (participants from the Moza-BC cohort) and 638 controls from the general population (from a World Health Organization stepwise approach to surveillance survey), recruited during 2014 to 2017, were investigated. Adjusted ORs (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results: Multiparity (≥6 vs. 0–1 live births) was a protective factor for the development of hormone receptor (HR)–positive (aOR = 0.22; 95% CI, 0.08–0.64) and HR-positive/HER2-negative tumors (aOR = 0.20; 95% CI, 0.06–0.68), whereas a higher educational level (≥8 vs. 0 schooling years) increased breast cancer risk across all subtypes (overall aOR = 1.98; 95% CI, 1.04–3.80). Higher weight and BMI were associated with a higher breast cancer risk among postmenopausal women (per 1-kg increase: aOR = 1.05; 95% CI, 1.02–1.08; per 1-kg/m2 increase: aOR = 1.11; 95% CI, 1.04–1.18, respectively), but were protective in premenopausal women (aOR = 0.98; 95% CI, 0.96–0.99; aOR = 0.95; 95% CI, 0.91–0.99, respectively), regardless of subtype. Higher height increased the risk of HR-negative tumors in postmenopause (per 10-cm increase: aOR = 2.81; 95% CI, 1.41–6.03). Conclusion: These results demonstrate the etiological heterogeneity of breast cancer among native African women, namely regarding the differential effect of multiparity, education, and body parameters in breast cancer risk. Impact: As the prevalence of obesity grows, these findings are important to inform public health policies on cancer prevention, by highlighting obesity as a modifiable risk factor for breast cancer among African women. The Moza-BC cohort study was supported by the Beginning Investigator Grant for Catalytic Research (BIG Cat) program, an AORTIC program with support from the U.S. NCI (grant number 59-210-6-004). The WHO-STEPS Survey was funded by the Mozambican Ministry of Health and by the WHO. In addition, this study was supported by national funding from FCT – Fundação para a Ciência e a Tecnologia, I.P., under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). Samantha Morais was cofunded by FEDER through the Operational Programme Competitiveness and Internationalization and FCT (POCI01-0145-FEDER-032358; PTDC/SAU-EPI/32358/2017). The funders had no involvement in the analysis and interpretation of data, writing of the report, or decision to submit the article for publication. The authors thank the Calouste Gulbenkian Foundation (Portugal) and partners Camões, Institute of Cooperation and Language, Portugal; Millennium BCP Foundation, Portugal; and Millennium BIM; Mozambique, for funding the short-term training program of Assucena Guisseve at the Centro Hospitalar Universitário de São João, under the Project “Improving the diagnosis and treatment of oncological diseases in Mozambique.” The authors also thank Dr. Maria Alice Franzoi, from the Institut Jules Bordet, for her comments on the article. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Objective This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. Methods A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. Results Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. Conclusions These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

The COVID‐19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID‐19 on the short‐term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin‐melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO‐Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID‐19) and 2020 (after COVID‐19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score‐adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow‐up to 31 October, there were 154 (11.8%) deaths observed before COVID‐19 and 131 (17.2%) after COVID‐19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20‐1.91) and 1.10 (0.86‐1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14‐4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14‐13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96‐3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46‐0.83). The higher overall short‐term mortality observed during the COVID‐19 pandemic largely reflects the effects of the epidemic on the case‐mix of patients being diagnosed with cancer., What's new The coronavirus disease 2019 (COVID‐19) pandemic, owing to efforts to limit the spread of disease, greatly restricted routine healthcare services, including those relevant to cancer diagnosis and treatment. The present study investigated the impact of these restrictions on the care of patients at the Portuguese Oncology Institute of Porto, one of the largest cancer‐care hospitals in Portugal. Cancer registry data reveal increased overall short‐term mortality during the pandemic. After COVID‐19, cancers were more often diagnosed at more advanced stages and were more often symptomatic. The differing case‐mix of patients during the COVID‐19 pandemic, however, warrants cautious interpretation of results.

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04, I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82, 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38, 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92, 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62, 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

Background. The cost of breast cancer care rises with higher stage at diagnosis; however, there are no real-world data regarding the cost of care according to breast cancer subtypes. This study aimed to estimate direct medical costs for early breast cancer care in the first 3 years after diagnosis according to subtype and stage, using patient-level data. Methods. Women with newly diagnosed stage I–III breast cancer, admitted in 2012 to a Portuguese cancer centre were prospectively followed within the NEON-BC cohort. The use of health resources was obtained from each patient’s clinical and administrative records and costs were computed. Tumours were classified into the classic subtypes (hormone receptor-positive (HR+)/HER2−; HER2-positive (HER2+); triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (luminal A-like; luminal B-like; HER2 enriched; basal like). Results. A total of 703 patients were included: 48.9% had stage I, 35.8% stage II and 15.2% stage III breast cancer; 76.4% had HR+/HER2−, 15.9% HER2+ and 7.7% TNBC. Median cost of care was €9215/patient in stage I, €13 019/patient in stage II and €15 011/patient in stage III and €10 540/patient in HR+/HER2−, €11 224/patient in TNBC and €41 513/patient in HER2+ breast cancer. Systemic therapy accounted for 69.2% of the cost of care among patients with HER2+, 12.0% among HR+/HER2− and 7.5% among TNBC patients. Similar differences were observed across surrogate intrinsic subtypes. Conclusions. The cost of early breast cancer care was mainly driven by the tumour subtype and, to a lesser extent, by stage. The median cost of care was fourfold higher among patients with HER2+ tumours compared with those with HR+/HER2− and TNBC. These data provide information for the economic evaluation of innovative treatments for early breast cancer and highlight the weight that targeted systemic therapy might have in the overall cost of care among patients with early breast cancer. This study was funded by the European Regional Development Fund (FEDER) through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education), under the project 'A 5-year prospective cohort study on the neurological complications of breast cancer: frequency and impact in patient-reported outcomes' (POCI-01-0145-FEDER-016867, Ref. PTDC/DTP-EPI/7183/2014), and national funding from FCT, under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020). SM and LL-C were also funded under the scope of the project 'NEON-PC Neuro- oncological complications of prostate cancer: longitudinal study of cognitive decline' (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017). An individual grant attributed to NA (SFRH/BD/119390/2016) was cofunded by FCT and the 'Programa Operacional Capital Humano' (POCH/FSE). Data management activities up to the first year of follow-up were supported by the Chair on Pain Medicine of the Faculty of Medicine, University of Porto and by the Grünenthal Foundation—Portugal.

Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA < 1.5 standard deviations (SD) of age- and education-specific normative values were considered to have probable cognitive impairment (PCI) and were referred for a comprehensive neuropsychological assessment. Data from the population-based cohort EPIPorto (n = 351 men aged ≥40 years, evaluated in 2013–2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer., This study was funded by the European Regional Development Fund through the Operational Program Competitiveness and Internationalization, national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project ‘NEON-PC-Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia-Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020) and ITR (LA/P/0064/2020), financed by national funds from FCT. A.C., C.L., and S.M. were funded under the scope of the project ‘NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). S.M. also received funding under EPIunit-Junior Research-Prog Financing (UIDP/04750/2020). An individual PhD grant attributed to N.A. (SFRH/BD/119390/2016) was funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE).

Migrants' health is attracting substantial global interest. We aimed to identify barriers and differences in healthcare services utilization between migrants and natives in a nationally representative sample using data from the National Health Survey 2014. A total of 18,165 participants providing information on country of birth and nationality were included, and comparison of healthcare services utilization was made by using participants born in Portugal and with Portuguese nationality as the reference group. Migrants reported a lower frequency of medical visits, a higher consumption of medication without a prescription and less use of preventive care services. The main reasons for not attending medical consultations among migrants were the absence of need and financial difficulties. This study illustrates inequalities in healthcare use among migrants in Portugal, and provides useful information for enlightening policymakers and healthcare providers to develop health policies that can address migrants' needs.

Background The main outcome of Helicobacter pylori infection, i.e. gastric cancer, is more frequent in men, but there is no comprehensive synthesis of the evidence on a potential role of sex in the acquisition and/or persistence of infection. Aims To quantify the association between sex and H. pylori infection in pediatric and adult populations, through systematic review and meta-analysis. Methods PubMed ® was searched, from inception to September 2015, to identify population-based studies reporting the prevalence and/or incidence of H. pylori infection in both sexes. Odds ratios (OR) or data to compute them were extracted; adjusted estimates were preferred, whenever available. The DerSimonian and Laird method was used to compute summary estimates and respective 95% confidence intervals (95%CI), separately for children and adults. Results Among a total of 244 studies, mostly cross-sectional, male sex was associated with a greater prevalence of H. pylori infection, both in children (102 studies, OR = 1.06, 95%CI: 1.01, 1.12, I 2 = 43.7%) and adults (169 studies, OR = 1.12, 95%CI: 1.09, 1.15, I 2 = 68.5%). An underrepresentation of studies showing a negative association between male sex and infection was observed (Egger’s test: p = 0.006). Conclusions Although further research is needed to understand the mechanisms by which sex may influence the acquisition and/or persistence of infection, our results support a small contribution of sex differences in the prevalence of infection to the male predominance of H. pylori -related outcomes, including gastric cancer.

The consumption of processed meat has been associated with noncardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Our study aims to quantify the association between meat consumption, namely white, red and processed meat, and the risk of gastric cancer, through individual participant data meta-analysis of studies participating in the “Stomach cancer Pooling (StoP) Project”. Data from 22 studies, including 11,443 cases and 28,029 controls, were used. Study-specific odds ratios (ORs) were pooled through a two-stage approach based on random-effects models. An exposure-response relationship was modeled, using one and two-order fractional polynomials, to evaluate the possible nonlinear association between meat intake and gastric cancer. An increased risk of gastric cancer was observed for the consumption of all types of meat (highest vs. lowest tertile), which was statistically significant for red (OR: 1.24; 95% CI: 1.00–1.53), processed (OR: 1.23; 95% CI: 1.06–1.43) and total meat (OR: 1.30; 95% CI: 1.09–1.55). Exposure-response analyses showed an increasing risk of gastric cancer with increasing consumption of both processed and red meat, with the highest OR being observed for an intake of 150 g/day of red meat (OR: 1.85; 95% CI: 1.56–2.20). This work provides robust evidence on the relation between the consumption of different types of meat and gastric cancer. Adherence to dietary recommendations to reduce meat consumption may contribute to a reduction in the burden of gastric cancer. Our study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), by the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB), by the Italian League for the Fight Against Cancer (LILT) and by the Associazione Industriale delle Carni e dei Salumi (ASSICA, to the Department of Clinical Sciences and Community Health, University of Milan). Our study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). AF (PD/BD/105823/2014) was awarded with an individual scholarship through national funding from FCT/MCTES. Individual grants attributed to ARC (SFRH/BD/102181/2014), and BP (SFRH/BPD/108751/2015) were funded by the FCT and the “Programa Operacional Capital Humano” (POCH/SE). SM was funded under the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline “ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Valentina Rosato was supported by a fellowship by the Italian Foundation for Cancer Research (FIRC #18104).

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54&ndash, 0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55&ndash, 0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56&ndash, 0.92), flavanols (OR = 0.77, 95% CI = 0.66&ndash, 0.88), flavanones (OR = 0.57, 95%CI = 0.44&ndash, 0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55&ndash, 0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57&ndash, 0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51&ndash, 1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58&ndash, 1.06). Further investigations from longitudinal data are needed to confirm this association.

Objective: To compare the incidence rates of gastric cancer among cancer survivors with those in the general population, and estimate the probability of a gastric second primary cancer being diagnosed 10 years after any other first primary cancer. Method: A cohort of first primary cancers (other than gastric) diagnosed in Northern Portugal between 2000 and 2006 (n = 64,648) was followed until 31/12/2012 for gastric second primary cancers. Incidence rates, standardized incidence ratios and the cumulative incidence of gastric second primary cancers were calculated. Results: Overall, 330 patients developed gastric second primary cancers (21.2% within two months). The incidence rate of gastric second primary cancers was higher within two months of the first primary cancer (standardized incidence ratios: 5.20 in males and 7.89 in females), particularly among survivors of cancers of the oesophagus, colon and rectum, than in the remaining period (standardized incidence ratios: 0.64 in males and 0.74 in females). The 10-year risk of a gastric second primary cancer was 0.6% (males: 0.7%; females: 0.4%). Conclusion: The incidence rate of gastric second primary cancers among cancer survivors was higher than in the general population only soon after the first primary cancer, and lower thereafter. Despite the high mortality, the probability of a gastric second primary cancer within 10-years of the first primary cancer was 0.6%. Resumen: Objetivo: Comparar las tasas de incidencia de cáncer gástrico entre los sobrevivientes de cáncer con las de la población general y estimar la probabilidad de que se diagnostique un segundo cáncer primario gástrico 10 años después de cualquier otro primer cáncer primario. Método: Se siguió una cohorte de pacientes con un primer cáncer primario (excluyendo los gástricos) en el norte de Portugal entre 2000 y 2006 (n = 64.648) hasta el 31/12/2012 para identificar un segundo cáncer primario gástrico. Se calcularon las tasas de incidencia, las razones de incidencia estandarizadas (RIE) y la incidencia acumulada de segundos cánceres primarios gástricos. Resultados: En total, 330 pacientes desarrollaron un segundo cáncer primario gástrico (21,2% en 2 meses). La tasa de incidencia de los segundos cánceres primarios gástricos fue mayor dentro de los 2 meses posteriores al primero (RIE: 5,20 en hombres y 7,89 en mujeres), en particular entre los sobrevivientes de cáncer de esófago, colon y recto, que en el período restante (RIE: 0,64 en hombres y 0,74 en mujeres). El riesgo a 10 años de un segundo cáncer primario gástrico fue del 0,6% (hombres: 0,7%; mujeres: 0,4%). Conclusiones: La tasa de incidencia de segundos cánceres primarios gástricos entre los sobrevivientes de cáncer fue más alta que en la población general solo poco después del primer cáncer, y más baja a partir de entonces. A pesar de la alta mortalidad, la probabilidad de un segundo cáncer primario gástrico a 10 años del primero fue del 0,6%.