Total Cancer Mortality Research Articles

Iron status in relation to cancer risk and mortality: Findings from a population‐based prospective study

While experimental evidence suggests potential carcinogenic effects of increased iron load, there is a lack of data on iron status and cancer risk from epidemiological studies. Here, we evaluated prediagnostic serum concentrations of ferritin, iron and transferrin as well as transferrin saturation (TSAT) in relation to cancer risk and mortality in a prospective study by multivariable Cox regression analyses. A case-cohort sample of the population-based EPIC-Heidelberg Study including a random subcohort (n = 2738) and incident cases of breast cancer (n = 627), prostate cancer (n = 554), lung cancer (n = 195), colorectal cancer (n = 256) and cancer death (n = 759) was used. Ferritin levels were inversely associated with breast cancer risk in the multivariable Cox regression model, with a hazard ratio (HR) of 0.67 [95% confidence interval: 0.49, 0.92] for women in the highest quartile compared to those in the lowest quartile. Neither ferritin nor the other markers of iron status were significantly associated with colorectal, prostate or lung cancer risk. An inverse association was observed between ferritin and total cancer mortality (HR: 0.70 [0.53, 0.92]). There were no significant overall associations between serum iron, transferrin or TSAT and cancer mortality. The present findings do not support the notion of increased iron load constituting a cancer risk factor in the general population. By contrast, our analyses revealed inverse associations between ferritin levels and breast cancer risk as well as cancer mortality.

European cancer mortality predictions for the year 2018 with focus on colorectal cancer

BackgroundWe projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methodsWe obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970–2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. ResultsEU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1382000 when compared with 1333362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100000 for 2018 (13.9 in 2012,+5.8%) and 94500 expected deaths, higher than the rate of 13.7 and 92700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100000 men (−6.7%) and 9.2 in women (−7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose+2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392300 cancer deaths were avoided compared with peak rates in the late 1980s. ConclusionWe predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and—above age 50years—organized screening may account for recent favourable colorectal cancer trends.

Associations of metabolic syndrome and C-reactive protein with mortality from total cancer, obesity-linked cancers and breast cancer among women in NHANES III.

Although metabolic syndrome (MetS) is a prognostic factor for cancer occurrence, the association of MetS and cancer mortality remains unclear. The purpose of this study was to evaluate whether MetS, components of MetS and C-reactive protein (CRP) are associated with cancer mortality in women. A total of 400 cancer deaths, with 140 deaths from obesity-linked-cancers (OLCas), [breast (BCa), colorectal, pancreatic and endometrial], linked through the National Death Index, were identified from 10,104 eligible subjects aged ≥18 years. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for cancer mortality. MetS was associated with increased deaths for total cancer [HR = 1.33, 95% confidence interval (CI) 1.04-1.70] and BCa [HR = 2.1, 95% CI, 1.09-4.11]. The risk of total cancer [HR = 1.7, 95% CI, 1.12-2.68], OLCas [HR = 2.1, 95% CI, 1.00-4.37] and BCa [HR = 3.8, 95% CI, 1.34-10.91] mortality was highest for women with all MetS components abnormal, compared to those without MetS. Linear associations of blood-pressure [HR = 2.5, 1.02-6.12, Quartile (Q) 4 vs Q1, p trend = 0.004] and blood-glucose [HR = 2.2, 1.04-4.60, Q4 vs. Q1, p trend = 0.04] with total-OLCas mortality were observed. A threefold increased risk of BCa mortality was observed for women with enlarged waist circumference, ≥100.9 cm, [HR = 3.5, 1.14-10.51, p trend = 0.008] and in those with increased blood glucose, ≥101 mg/dL, [HR = 3.2, 1.11-9.20, p trend = 0.03] compared to those in Q1. None of the components of MetS were associated with total-cancer mortality. CRP was not associated with cancer mortality. In conclusion, MetS is associated with total-cancer and breast-cancer mortality, with waist circumference, blood pressure and blood glucose as independent predictors of OLCas and BCa mortality.

Prognostic Value of Cyclin D1 and CD44 Expression in Gastric Adenocarcinoma

Worldwide, gastric carcinoma (GC) is the 5th most common malignancies in both sexes representing 6.8% of the total fatalities and is the 3rd leading cause of cancer death representing 8.8% of total fatalities. In Egypt, GC considers the 12th leading cause of cancer death representing 2.2% of the total cancer mortality. A growing body of evidence supports that cancer stem cells (CSCs) are resistant to chemotherapy or radiation, and the cell adhesion molecule CD44 has been identified as a cell surface marker associated with cancer stem cell in several types of tumors including gastric cancer. CD44 regulates gastric stem cell proliferation by increasing cyclin D1 expression which represents an important regulatory protein in the cell cycle transition from G1 phase to S phase. This study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer. Forty formalin-fixed and paraffin-embedded gastric tissues, obtained from patients who underwent endoscopic resection or surgical resection, constituted the group of our study. The immunohistochemical expression of cyclin D1 and CD44 was examined and correlated with clinical-pathological parameters and outcome of the patients. Overexpression of CD44 and cyclin D1 was noted (in of 55 and 50% respectively). Cyclin D1 and CD44 positive expressions in GC were positively correlated with tumor differentiation (p = 0.020, p = 0.004 respectively), TNM stage (p < 0.001 for both), poor survival (p < 0.001 for both), and with increased rate of recurrence (p = 0.020, p = 0.005 respectively). CD44 and cyclin D1 were associated with poor prognosis in gastric cancer, and so, they comprise an attractive target for anticancer drug development.

Enhancing the Infrastructure of the Atherosclerosis Risk in Communities (ARIC) Study for Cancer Epidemiology Research: ARIC Cancer.

Background: We describe the expansion of the Atherosclerosis Risk in Communities (ARIC) Study into a cancer cohort. In 1987 to 1989, ARIC recruited 15,792 participants 45 to 64 years old to be sex (55% female), race (27% black), and geographically diverse. ARIC has exceptional data collected during 6 clinical visits and calls every 6 months, repeated biospecimens, and linkage to Medicare claims data.Methods: We established a Cancer Coordinating Center to implement infrastructure activities, convened a Working Group for data use, leveraged ARIC staff and procedures, and developed protocols. We initiated a cancer-specific participant contact, added questions to existing contacts, obtained permission to collect medical records and tissue, abstracted records, linked with state cancer registries, and adjudicated cases and characterizing data.Results: Through 2012, we ascertained and characterized 4,743 incident invasive, first, and subsequent primary cancers among 4,107 participants and 1,660 cancer-related deaths. We generated a total cancer incidence and mortality analytic case file, and analytic case files for bladder, breast, colorectal, liver, lung, pancreas, and prostate cancer incidence, mortality, and case fatality. Adjudication of multiple data sources improved case records and identified cancers not identified via registries. From 2013 onward, we ascertain cases from self-report coupled with medical records. Additional cancer registry linkages are planned.Conclusions: Compared with starting a new cohort, expanding a cardiovascular cohort into ARIC Cancer was an efficient strategy. Our efforts yielded enhanced case files with 25 years of follow-up.Impact: Now that the cancer infrastructure is established, ARIC is contributing its unique features to modern cancer epidemiology research. Cancer Epidemiol Biomarkers Prev; 27(3); 295-305. ©2017 AACR.

Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality.

INTRODUCTIONThe obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.METHODSProspective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score.RESULTSAmong 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 – 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 – 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality.CONCLUSIONSLeptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study.IMPACTOur observed increased risk of cancer mortality associated with higher serum resistin levels among Blacks suggests that if validated in larger cohorts, clinical strategies focused on resistin control may be a promising cancer prevention strategy.

Cancer mortality in Europe, 1970-2009: an age, period, and cohort analysis.

The aim of this study was to interpret long-term trends in cancer mortality. We analyzed age, period of death, and cohort of birth effects for 18 major cancer sites and all neoplasms combined in the European Union and 16 European countries over the period 1970-2009 using data from the WHO mortality database. We used a log-linear Poisson model with a likelihood penalizing function to solve the identifiability problem. The present comprehensive analysis confirms the appreciable declines of cancer mortality since the late 1980s in most European countries. For several major sites, the declines were appreciably greater for cohort effects than for period ones. This reflects - besides the inherent characteristics of the model used - a major impact of tobacco smoking on total cancer mortality, particularly in men, as the role of tobacco in mortality of subsequent generations is largely - although not totally - a cohort effect. For neoplasms largely affected by improvements in management and therapy (e.g. testis, Hodgkin lymphoma, leukemia, but also breast and colorectal cancer), a favorable period effect is evident. However, there is also a cohort effect as the advancements have been generally greater in younger generations. For several cancer sites, there were considerable differences in cohort and period effects across Europe, and particularly high age-specific estimates were observed in eastern countries.

Poultry and Fish Consumption in Relation to Total Cancer Mortality: A Meta-Analysis of Prospective Studies

ABSTRACTObservational studies on the association between fish and poultry intake and the risk of total cancer mortality have been reported with mixed results. Thus, we aimed to assess this association by conducting a meta-analysis of prospective studies. We performed a literature search on PubMed database through February 1, 2017 to identify relative prospective studies. A random-effects model was used to calculate the summary estimates. We identified fourteen prospective studies involving 2,378,204 participants and 96,712 cancer mortality events. Comparing the highest category of consumption with lowest category, pooled relative risk (RR) of total cancer mortality was 0.99 (95% confidence interval [CI], 0.94–1.05) for fish (10 studies) and 0.96 (95% CI, 0.93–1.00) for poultry (8 studies), respectively. However, we failed to identify any dose–response association based on a limited number of eligible studies, with a pooled RR of 0.98 (95% CI, 0.92–1.05) and 0.97 (95% CI, 0.88–1.07) for each 100 g per day increment in fish and poultry consumption, respectively. In summary, this meta-analysis indicates that consumption of either fish or poultry is not substantially associated with lower risk of total cancer mortality. The observed weak inverse association for high poultry consumption needs to be verified in additional large prospective studies.

Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC\u2013Heidelberg cohort

BackgroundCirculating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.MethodsWe selected a case-cohort sample out of the prospective EPIC–Heidelberg study, including a random subcohort (n = 2739), and cases of cancer (n = 1632), cancer mortality (n = 761), CVD (n = 1070), and CVD mortality (n = 381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.ResultsHigh levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HRapoB 0.71, 95% CI 0.52–0.98; HRTG 0.65, 0.46–0.92; and HRHDL 1.39, 1.01–1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HRLp(a) 1.43, 1.02–2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HRapo(a) 0.52, 0.30–0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HRTC 0.71, 0.54–0.94; HRHDL 0.67, 0.50–0.91; HRapo(a) 0.71, 0.54–0.93; and HRLp(a) 0.74, 0.57–0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.ConclusionsThis prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.

Association between Spot urine Phytoestrogens as Biomarkers on Their Dietary Intake on the Risk of Death from Cancer and Cardiovascular Disease

This study suggests that phytoestrogen intake alters cancer and cardiovascular risk. This study investigated the associations of urinary phytoestrogens with total cancer (n = 198), cardiovascular (n = 152), and all-cause (n = 363) mortality among 5179 participants in the continuous National Health and Nutrition Examination Survey Canada (2009–2014). Methods Urinary phytoestrogens were measured using high-performance liquid chromatography with tandem mass spectrometric detection. Survival analysis was per-formed to evaluate hazard ratios (HRs) and 95 % confi-dence intervals (CIs) for each of the three outcomes in relation to urinary phytoestrogens. Results: After adjustment for confounders, higher urinary concentrations of total enterolignans were associated with a reduced risk of death from cardiovascular disease (HR for tertile 3 vs. tertile 10.48; 95 % CI 0.24, 0.97), whereas higher urinary concentrations of total isoflavones (HR for tertile 3 vs. tertile 12.14; 95 % CI 1.03, 4.47) and daidzein (HR for tertile 3 vs. tertile 12.05; 95 % CI 1.02, 4.11) were associated with an increased risk death from Cardiovascular Disease. A reduction in all-cause mortality was observed for elevated urinary concentrations of total enterolignans (HR for tertile 3 vs. tertile 10.65; 95 % CI 0.43, 0.96) and enterolactone (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.44, 0.97). Conclusions: Some urinary phytoestrogens were associ-ated with cardiovascular and all-cause mortality in a rep-resentative sample of the Canadian population. This is one of the first studies that used urinary phytoestrogens as biomarkers of their dietary intake to evaluate the effect of these bioac-tive compounds on the risk of death from cancer and car-diovascular disease.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality

Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality. To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials. Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median). All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization. Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. clinicaltrials.gov Identifier: NCT00000611.

Cancer mortality predictions for 2017 in Latin America

From most recent available data, we predicted cancer mortality statistics in selected Latin American countries for the year 2017, with focus on lung cancer. We obtained death certification data from the World Health Organization and population data from the Pan American Health Organization database for all neoplasms and selected cancer sites. We derived figures for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela. Using a logarithmic Poisson count data joinpoint model, we estimated number of deaths and age-standardized (world population) mortality rates in 2017. Total cancer mortality rates are predicted to decline in all countries. The highest mortality rates for 2017 are in Cuba, i.e. 132.3/100 000 men and 93.3/100 000 women. Mexico had the lowest predicted rates, 64.7/100 000 men and 60.6/100 000 women. In contrast, the total number of cancer deaths is expected to rise due to population ageing and growth. Men showed declines in lung cancer trends in all countries and age groups considered, while only Colombian and Mexican women had downward trends. Stomach and (cervix) uteri rates are predicted to continue their declines, though mortality from these neoplasms remains comparatively high. Colorectal, breast and prostate cancer rates were predicted to decline moderately, as well as leukaemias. There was no clear pattern for pancreatic cancer. Between 1990 and 2017 about 420 000 cancer deaths were avoided in 5 of the 7 countries, no progress was observed in Brazil and Cuba. Cancer mortality rates for 2017 in seven selected Latin American countries are predicted to decline, though there was appreciable variability across countries. Mortality from major cancers-including lung and prostate-and all cancers remains comparatively high in Cuba, indicating the need for improved prevention and management.

Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial

Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence. We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose-response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017). Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p<0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p<0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26-41% and of interleukin 6 of 25-43% (p<0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio [HR] 0·49 [95% CI 0·31-0·75]; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 [95% CI 0·39-0·97]; p=0·034) and 300 mg groups (HR 0·33 [95% CI 0·18-0·59]; p<0·0001; p<0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 [95% CI 0·10-0·54]; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 [95% CI 0·83-1·06]; p=0·31). Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required. Novartis Pharmaceuticals.

Educational inequality in cancer mortality: a record linkage study of over 35 million Italians.

Large studies are needed to evaluate socioeconomic inequality for site-specific cancer mortality. We conducted a longitudinal census-based national study to quantify the relative inequality in cancer mortality among educational levels in Italy. We linked the 2011 Italian census with the 2012 and 2013 death registries. Educational inequality in overall cancer and site-specific cancer mortality were evaluated by computing the mortality rate ratio (MRR). A total of 35,708,445 subjects aged 30-74years and 147,981cancer deaths were registered. Compared to the lowest level of education (none or primary school), the MRR for all cancers in the highest level (university) was 0.57 (95% CI 0.55; 0.58) in men and 0.84 (95% CI 0.81; 0.87) in women. Higher education was associated with reduced risk of mortality from lip, oral cavity, pharynx, oesophagus, stomach, colon and liver in both sexes. Higher education (university) was associated with decreased risk of lung cancer in men (MRR: 0.43, 95% CI 0.41; 0.46), but not in women (MRR: 1.00, 95% CI 0.92; 1.10). Highly educated women had a reduced risk of mortality from cervical cancer than lower educated women (MRR: 0.39, 95% CI 0.27; 0.56), but they had a similar risk for breast cancer (MRR: 1.01, 95% CI 0.94; 1.09). Education is inversely associated with total cancer mortality, and the association was stronger in men. Different patterns and trends in tobacco smoking in men and women account for at least most of the gender differences.

Evolution of socioeconomic inequalities in site-specific cancer mortality among Belgian women between 1991 and 2008 using a fundamental cause approach.

According to the "fundamental cause theory", emerging knowledge on health-enhancing behaviours and technologies results in persisting and even widening health disparities, favouring the higher socioeconomic groups. This study aims to assess (trends in) socioeconomic inequalities in site-specific cancer mortality in Belgian women. Data were derived from record linkage between the Belgian census and register data on mortality for 1991-1997 and 2001-2008 for all Belgian female inhabitants aged 50-79years. Both absolute and relative inequalities by education and housing conditions were calculated. The results revealed persisting socioeconomic inequalities in total and site-specific cancer mortality. As expected, these inequalities were larger for the more preventable cancer sites. Generally, socioeconomic inequalities remained quite stable between the 1990s and the 2000s, although for some preventable cancer sites (e.g., uterus and oesophagus) a significant increase in inequality was observed. These persisting socioeconomic inequalities are likely due to differences in exposure to risk factors and unhealthy behaviours, and access and utilization of healthcare across the social strata. Since equality in health should be a priority for a fair public health policy, efforts to reduce inequalities in risk behaviours and access and use of health care should remain high on the agenda.

PARTITIONING OF TIME TRENDS IN MORTALITY OF LUNG CANCER AMONG OLDER U.S. ADULTS

Direct evaluation of lung cancer mortality from SEER data is challenging because of uncertainties in evaluating the population at risk at the time of death We overcome this problem by proposing a new approach for the calculation of cancer-specific mortality rates through the evaluation of multiple components contributing to total mortality and applying it to lung cancer patients. Specifically, the time-trend of lung cancer mortality is the result of three competing processes: changes in incidence rate, stage-specific survival, and ascertainment at early stages. Our approach estimates the contribution of each of the above components to the overall mortality trend. Using SEER data, we found that lung cancer mortality increases in females and decreases in males over the study period (1988–2012). The main contributions to the change in mortality trends for both genders are incidence rates (increasing in females and decreasing in males). Trends in incidence explain more than 50% of total lung cancer mortality trend. The remaining percentages are explained by increased ascertainment at early stages, improved survival, and prevailing trends in mortality for the general population. These patterns held for analysis of histotype-specific groups (adenocarcinoma, squamous-cell carcinoma, and small-cell carcinoma) with the exception of the increased role of incidence in adenocarcinoma in males and ascertainment at early stages for squamous-cell and small-cell carcinoma. The methodology developed in this study increases the range of analysis that can be accomplished with SEER data and can serve as an additional tool for improvement in the quality of health outcomes research.

Strategies for prevention of gastrointestinal cancers in developing countries: a systematic review.

BackgroundGastrointestinal cancers account for one third of total cancer incidence and mortality in developing countries. To date, there is no systematic synthesis of evidence regarding strategies to prevent gastrointestinal cancers in developing countries. We aimed to provide a systematic overview of studies evaluating strategies for prevention or early detection of the three most common gastrointestinal cancers (gastric, liver and colorectal cancer) in developing countries.MethodsWe searched MEDLINE, Web of Science and WHO Global Index Medicus databases for relevant articles published until October 2016 using combinations of the search terms “gastrointestinal”, “digestive system”, “gastric”, “liver”, “colorectal”, “cancer”, “prevention”, “early detection” and “developing country” (including names).ResultsOverall, 73 articles met the inclusion criteria, providing information on short– and long–term outcomes (up to 30 years) from various intervention studies (∼45% randomized). Trials on hepatitis B vaccination consistently showed vaccine efficacy over time and indicated long–term preventive effects on liver cancer incidence that start to become measurable at the population level. Studies on anti–H. pylori treatment suggested a reduction in gastric cancer incidence reaching statistical significance after long–term follow–up, while evidence regarding a preventive effect in persons with precancerous lesions is still inconclusive. The studies regarding colorectal cancer focused on early detection, ∼90% of which were restricted to intermediate endpoints.ConclusionIn conclusion, there were a number of studies on gastric and liver cancer prevention in developing countries showing promising results after long–term follow–up. Important next steps include pooled meta–analyses as far as possible given the heterogeneity between studies as well as implementation research.

Resting heart rate and the risk of cardiovascular disease, total cancer, and all-cause mortality – A systematic review and dose–response meta-analysis of prospective studies

Background and aimEpidemiological studies have reported increased risk of cardiovascular disease, cancer and all-cause mortality with greater resting heart rate, however, the evidence is not consistent. Differences by gender, adjustment for confounding factors, as well as the potential impact of subclinical disease are not clear. A previous meta-analysis missed a large number of studies, and data for atrial fibrillation have not been summarized before. We therefore aimed to clarify these associations in a systematic review and meta-analysis of prospective studies. Methods and resultsPubMed and Embase were searched up to 29 March 2017. Summary RRs and 95% confidence intervals (CIs) were calculated using random effects models. Eighty seven studies were included. The summary RR per 10 beats per minute increase in resting heart rate was 1.07 (95% CI: 1.05–1.10, I2 = 61.9%, n = 31) for coronary heart disease, 1.09 (95% CI: 1.00–1.18, I2 = 62.3%, n = 5) for sudden cardiac death, 1.18 (95% CI: 1.10–1.27, I2 = 74.5%, n = 8) for heart failure, 0.97 (95% CI: 0.92–1.02, I2 = 91.4%, n = 9) for atrial fibrillation, 1.06 (95% CI: 1.02–1.10, I2 = 59.5%, n = 16) for total stroke, 1.15 (95% CI: 1.11–1.18, I2 = 84.3%, n = 35) for cardiovascular disease, 1.14 (95% CI: 1.06–1.23, I2 = 90.2%, n = 12) for total cancer, and 1.17 (95% CI: 1.14–1.19, I2 = 94.0%, n = 48) for all-cause mortality. There was a positive dose–response relationship for all outcomes except for atrial fibrillation for which there was a J-shaped association. ConclusionThis meta-analysis found an increased risk of coronary heart disease, sudden cardiac death, heart failure, atrial fibrillation, stroke, cardiovascular disease, total cancer and all-cause mortality with greater resting heart rate.

White Blood Cell Count and Total and Cause-Specific Mortality in the Women's Health Initiative.

White blood cell (WBC) count appears to predict total mortality and coronary heart disease (CHD) mortality, but it is unclear to what extent the association reflects confounding by smoking, underlying illness, or comorbid conditions. We used data from the Women's Health Initiative to examine the associations of WBC count with total mortality, CHD mortality, and cancer mortality. WBC count was measured at baseline in 160,117 postmenopausal women and again in year 3 in 74,375 participants. Participants were followed for a mean of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline WBC count and of the mean of baseline+year 3 WBC count. High deciles of both baseline and mean WBC count were positively associated with total mortality and CHD mortality, whereas the association with cancer mortality was weaker. The association of WBC count with mortality was independent of smoking and did not appear to be influenced by previous disease history. The potential clinical utility of this common laboratory test in predicting mortality risk warrants further study.

Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design

Background: Objective was to quantify biases in screening for gastric cancer when comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as primary test.Methods: In mid 1990s, all men aged 51–65 years from two Finnish cities were invited to SPGI screening. Mortality and premature mortality in attenders were compared to nonattenders. Efficacy of screening was studied by 15 years’ follow-up of standardized mortality ratio (SMR) and potential years of life lost (PYLL) due to gastric cancer. Bias due to selective attendance was quantified using corrective coefficients based on total cancer incidence and mortality, and gastric cancer-specific incidence and mortality for total population and nonattenders.Results: In 1994–1996, men aged 51–65 years (16,872) were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were referred for treatment due to abnormal focal lesions. Attributable proportions in reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%. After correcting for selective participation, attributable proportions were reduced to 23% and 39%.Conclusions: Biomarker screening by low SPGI among middle-aged men followed by upper gastrointestinal endoscopy decreased long-term and premature mortality due to gastric cancer. However, in spite of methodological corrections done, the results do not justify any firm conclusions or recommend general screening programs. Randomized trials are warranted for this purpose.