Search

Mouse models are vital for assessing risk from environmental carcinogens, including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human–mouse difference in radiation‐related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data on cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age‐related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per‐lifespan basis (0.72‐ and 0.71‐fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 years per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species‐independent radiation‐induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation‐associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans. [ABSTRACT FROM AUTHOR]

Background and aims: Studies on cancer incidence and mortality among people with opioid use‐related disorders are lacking. We aimed to measure cancer‐specific incidence, mortality and survival among people diagnosed with opioid use‐related disorders in Norway during 2010–18. Design and setting: This was a cohort study conducted in Norway during 2010–18. Participants: Individuals (n = 20 710) diagnosed with opioid use‐related disorders. Measurements: We conducted a cohort study utilizing a data‐linkage of national health and population registers. Information on opioid use‐related disorders was extracted from specialized healthcare, malignancies from the Cancer Registry of Norway and deaths from Cause of Death Registry. Cancer incidence and mortality were compared with the general population by calculating sex‐specific age‐standardized incidence (SIR) and mortality (SMR) ratios. One‐year survival rates were computed. Findings Compared with the general population, people with opioid use‐related disorders were at an increased risk of developing cancer overall [SIR = 1.2, 95% confidence interval (CI) = 1.1–1.3] with a higher than twofold cancer mortality rate (SMR = 2.3, 95% CI = 2.0–2.7). Excess risk was observed for liver (12.6, 95% CI = 9.1–17.0), larynx (4.7, 95% CI = 1.7–10.2), lung (3.5, 95% CI = 2.8–4.3) and pancreas cancer (2.6, 95% CI = 1.6–4.0), whereas reduced risk was found for melanoma (0.5, 95% CI = 0.3–0.9), breast (0.6, 95% CI = 0.4–0.9) and prostate cancers (0.3, 95% CI = 0.1–0.4). Site‐specific SMRs were significantly elevated for liver (12.3, 95% CI = 8.5–17.2), lung (3.9, 95% CI = 3.0–5.0), pancreas (3.0, 95% CI = 1.7–4.8) and colon cancers (1.9, 95% CI = 1.1–3.1). The average 1‐year survival rate after a cancer diagnosis was low in liver, pancreas and colon cancer, ranging from 10 to 15% less than that of the general population. Conclusions: In Norway, cancer incidence and cancer‐related mortality appear to be elevated among individuals with opioid use‐related disorders. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The relationship between α‐Klotho (αK) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum αK protein levels with all‐cause and cause‐specific mortality in a cohort representative of the US population.We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016. A nonlinear association between mortality and αK levels as a quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio.Of the 13 749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29.7 (6.7) kg/m2, and αK was 0.85 (0.31) ng/mL. In the adjusted Cox proportional hazards model with quadratic αK, we found a U‐shaped relationship between all‐cause mortality and αK levels (continuous αK hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.37, 0.85; P = .007; squared‐αK HR = 1.25, 95% CI: 1.11, 1.41; P < 0.001). A similar U‐shaped relationship was noted between αK and cancer mortality in the adjusted Cox proportional hazards model (continuous αK HR = 0.45, 95% CI: 0.19, 1.06; P = 0.07; squared αK HR = 1.32, 95% CI: 1.07, 1.61; P = 0.009). No relationship was present with cardiovascular or other‐cause mortality.In this large diverse cohort, we report a U‐shaped relationship between αK with all‐cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed. [ABSTRACT FROM AUTHOR]

Aims: A higher risk of cancer among patients with heart failure (HF) has been suggested in recent community‐based studies. This study aimed to investigate the impact of HF during hospitalization with acute coronary syndrome (ACS) on the long‐term cancer risk. Methods and results: The study included 572 patients admitted with ACS to three Italian hospitals, discharged cancer‐free, and prospectively followed for 24 years or until death. All but three patients completed the follow‐up, which represented 6440 person‐years (mean age: 66 ± 12 years; 70% males). Baseline HF was diagnosed in 192 (34%) patients. A total of 129 (23%) patients developed cancer (103 without HF and 26 with HF), and 107 (19%) patients died due to it (81 without HF and 26 with HF). The incidence rates for cancer onset and cancer death were not different according to HF status. Cox regression analysis revealed no association between HF or left ventricular ejection fraction (LVEF) and cancer risk. In addition, no difference in cancer risk was observed among patients with HF with preserved ejection fraction, HF with mildly reduced ejection fraction, and HF with reduced ejection fraction. In competing risk regression analysis, the risk of cancer onset associated with HF was sub‐hazard ratio (SHR) 0.47 [95% confidence interval (CI): 0.30–0.72; P = 0.001] and SHR 1.02 (95% CI: 1.01–1.04; P = 0.002) with LVEF. Results were the same in the adjusted model. Yet the fully adjusted model showed an attenuated association between cancer death and HF (SHR: 0.63; 95% CI: 0.37–1.05; P = 0.08) and LVEF (SHR: 1.02; 95% CI: 0.99–1.06; P = 0.08). Consistent results were obtained after using propensity score matching analysis that created 192 pairs. A negative interaction between age and HF and a positive interaction between age and LVEF for cancer risk have also been found. Conclusions: An inverse association between baseline HF and long‐term cancer risk has been observed among the ABC Study on heart disease patients who were followed for 24 years after ACS. [ABSTRACT FROM AUTHOR]

Background Objectives Search strategy Selection criteria Data collection and analysis Main results Conclusions The associations between hysterectomy and cardiovascular disease (CVD) and mortality remains unlcear and a meta‐analysis with cohort studies is lacking.This study aimed to conduct a systematic review and meta‐analysis of cohort studies to investigate the relationship between hysterectomy and CVD, coronary heart disease (CHD), stroke, heart failure, and all‐cause, cardiovascular and cancer mortality. We further explored the effect of oophorectomy on the association between hysterectomy and these health outcomes.PubMed, EMBASE and Web of Science were searched up to 24 July 2023.Cohort studies.Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using a random‐effects model. We used I2 to assess the heterogeneity between studies.Forty‐three studies were included in the meta‐analysis. Hysterectomy was significantly associated with an increased risk of CVD (pooled HR 1.11, 95% CI 1.09–1.13; n = 6; I2 = 0) and stroke (HR 1.09, 95% CI 1.04–1.14; n = 7; I2 = 52%), but with a decreased risk of cancer mortality (HR 0.93, 95% CI 0.86–1.00; n = 4; I2 = 81%). No significant association was observed between hysterectomy and CHD (n = 10; I2 = 83%), all‐cause mortality (n = 8; I2 = 81%) or cardiovascular mortality (n = 7; I2 = 89%). Hysterectomy with and without oophorectomy was significantly associated with CVD and stroke risk, but showed a larger effect size for hysterectomy with oophorectomy. A significantly increased risk of CHD was observed in the subgroup of hysterectomy with oophorectomy, but not for the subgroup of hysterectomy alone.Hysterectomy may increase the risk of CVD, CHD and stroke, but not all‐cause, cardiovascular or cancer mortality. Hysterectomy with oophorectomy may have a higher risk of CVD, CHD and stroke than hysterectomy alone. However, the results on CHD and mortality related to hysterectomy should be interpreted cautiously because of the high level of heterogeneity and unstable subgroup analyses. [ABSTRACT FROM AUTHOR]

Aim: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all‐cause and cause‐specific mortality. Materials and Methods: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high‐density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. Results: The median follow‐up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U‐shaped relationship between CVAI and all‐cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%–25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0–27.0) higher risk of CVD death. In subgroup analysis, a J‐shaped and inverted U‐shaped relationship for all‐cause mortality and cancer mortality was observed in the group aged < 60 years. Conclusions: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all‐cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes. [ABSTRACT FROM AUTHOR]

Background: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long‐term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. Methods: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri‐yearly, bi‐yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. Results: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2‐year delay resulted in a prostate cancer death risk of 2.46%–2.69% 5 years after progression detection and a 10‐year risk of 5.75%–5.91%. A 4‐year delay led to an approximately 8% greater 5‐year risk and an approximately 25% greater 10‐year risk. Conclusion: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut‐off for a "safe" detection delay could not be identified. [ABSTRACT FROM AUTHOR]

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8‐fold excess mortality (95% CI: 1.59‐2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81‐9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97‐8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03‐6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P <.01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic status (SES) is associated with a range of health outcomes, including cancer diagnosis and survival. However, the evidence for this association is inconsistent between countries with and without single‐payer health care systems. In this study, the relationships between neighborhood‐level income, cancer stage at diagnosis, and cancer‐specific mortality in Alberta, Canada, were evaluated. Methods: The Alberta Cancer Registry was used to identify all primary cancer diagnoses between 2010 and 2020. Average neighborhood income was determined by linking the Canadian census to postal codes and was categorized into quintiles on the basis of income distribution in Alberta. Multivariable multinomial logistic regression was used to model the association between income quintile and stage at diagnosis, and the Fine–Gray proportional subdistribution hazards model was used to estimate the association between SES and cancer‐specific mortality. Results: Out of the 143,818 patients with cancer included in the study, those in lower income quintiles were significantly more likely to be diagnosed at stage III (odds ratio [OR], 1.07; 95% CI [confidence interval], 1.06–1.09) or IV (OR, 1.12; 95% CI, 1.11–1.14) after adjusting for age and sex. Lower income quintiles also had significantly worse cancer‐specific survival for breast, colorectal, liver, lung, non‐Hodgkin lymphoma, oral cavity, pancreas, and prostate cancers. Conclusions: Disparities were observed in cancer outcomes across neighborhood‐level income groups in Alberta, which demonstrates that health inequities by SES exist in countries with single‐payer health care systems. Further research is needed to better understand the underlying causes and to develop strategies to mitigate these disparities. The association between socioeconomic status and cancer outcomes in countries with single‐payer health care systems is inconsistent. In this analysis, lower socioeconomic status was found to be associated with both stage at diagnosis and cancer‐specific mortality of major cancer types in a Canadian province. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an association between living alone and cancer mortality; however, findings by sex and race/ethnicity have generally been inconsistent, and data by socioeconomic status are sparse. The association between living alone and cancer mortality by sex, race/ethnicity, and socioeconomic status in a nationally representative US cohort was examined. Methods: Pooled 1998–2019 data for adults aged 18–64 years at enrollment from the National Health Interview Survey linked to the National Death Index (N = 473,648) with up to 22 years of follow‐up were used to calculate hazard ratios (HRs) for the association between living alone and cancer mortality. Results: Compared to adults living with others, adults living alone were at a higher risk of cancer death in the age‐adjusted model (HR, 1.32; 95% CI, 1.25–1.39) and after additional adjustments for multiple sociodemographic characteristics and cancer risk factors (HR, 1.10; 95% CI, 1.04–1.16). Age‐adjusted models stratified by sex, poverty level, and educational attainment showed similar associations between living alone and cancer mortality, but the association was stronger among non‐Hispanic White adults (HR, 1.33; 95% CI, 1.25–1.42) than non‐Hispanic Black adults (HR, 1.18; 95% CI, 1.05–1.32; p value for difference <.05) and did not exist in other racial/ethnic groups. These associations were attenuated but persisted in fully adjusted models among men (HR, 1.13; 95% CI, 1.05–1.23), women (HR, 1.09; 95% CI, 1.01–1.18), non‐Hispanic White adults (HR, 1.13; 95% CI, 1.05–1.20), and adults with a college degree (HR, 1.22; 95% CI, 1.07–1.39). Conclusions: In this nationally representative study in the United States, adults living alone were at a higher risk of cancer death in several sociodemographic groups. In a nationally representative study with up to 22 years of mortality follow‐up, US working‐age adults experiencing social isolation, measured as living alone, were at a higher risk of cancer death than adults living with others. This association persisted among non‐Hispanic White adults and adults with higher education even after accounting for differences in a wide range of sociodemographic, behavioral, and health characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is the second leading cause of death in the United States, and the disease burden is elevated in Appalachian Kentucky, due in part to health behaviors and inequities in social determinants of health. This study's goal was to evaluate Appalachian Kentucky's cancer burden compared to non‐Appalachian Kentucky, and Kentucky compared to the United States (excluding Kentucky). Methods: The following data were analyzed: annual all‐cause and all‐site cancer mortality rates from 1968 to 2018; 5‐year all‐site and site‐specific cancer incidence and mortality rates from 2014 to 2018; aggregated screening and risk factor data from 2016 to 2018 for the United States (excluding Kentucky), Kentucky, non‐Appalachian Kentucky, and Appalachian Kentucky; and human papilloma virus vaccination prevalence by sex from 2018 for the United States and Kentucky. Findings: Since 1968, the United States has experienced a large decrease in all‐cause and cancer mortality, but the reduction in Kentucky has been smaller and slower, driven by even smaller and slower reductions within Appalachian Kentucky. Appalachian Kentucky has higher overall cancer incidence and mortality rates and higher rates for several site‐specific cancers compared to non‐Appalachian Kentucky. Contributing factors include screening rate disparities and increased rates of obesity and smoking. Conclusions: Appalachian Kentucky has experienced persistent cancer disparities, including elevated all‐cause and cancer mortality rates for 50+ years, widening the gap between this region and the rest of the country. In addition to addressing social determinants of health, increased efforts aimed at improving health behaviors and increased access to health care resources could help reduce this disparity. [ABSTRACT FROM AUTHOR]

Objectives: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality‐to‐incidence ratio (MIR), which is rare in the literature. Methods: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. Results: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92–0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23–1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30–1.42). Conclusion: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities. [ABSTRACT FROM AUTHOR]

Background: Kidney function is associated with clinical outcomes in patients with cancer. Objectives: This study aimed to assess the association between kidney function decline and cancer‐related mortality among community‐dwelling elderly individuals. Design: This was a retrospective longitudinal cohort study. Participants: The 61,988 participants were from an elderly health examination database in Taipei City from 2005 to 2012. Measurements Multivariable logistic regression was used to assess the association between baseline covariates and rapidly deteriorating estimated glomerular filtration rate (eGFR). In addition, Cox proportional hazards model and the Fine–Gray model were used to quantify the effects of covariates on total cancer mortality and six specific cancer mortalities. Results: During the follow‐up period, 1482 participants died of cancer. Their baseline average eGFR was 73.8 ± 19.9 mL/min/1.73 m2, and 18.3% had rapid renal function decline (≥5 mL/min/1.73 m2 per year). Rapid renal function decline was positively related to age, baseline eGFR, proteinuria, hypertension, waist circumferences, high log triglyceride levels, and diabetes mellitus (DM) history. In Cox proportional hazard models, participants with rapid eGFR decline had an increased risk of cancer mortality [hazard ratio (95% CI): 1.97 (1.73, 2.24); p < 0.001] compared to those without rapid eGFR decline. In the analysis of site‐specific cancer mortality risk, rapid eGFR decline was associated with six site‐specific cancer mortality, namely gastrointestinal tract, hepatobiliary, lung, prostate, urinary tract, and hematological malignancies. Conclusions: Elderly individuals with rapid kidney function decline had higher cancer mortality risks. Serial assessments of dynamic changes in eGFR might provide information relevant for cancer prognosis. [ABSTRACT FROM AUTHOR]

Aim: To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea. Methods: A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models. Results: Both men and women with alcoholic liver disease had an elevated risk of all‐cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose–response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men. Conclusions: Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease. [ABSTRACT FROM AUTHOR]

Background: Klotho has both anticancer and hormone‐like functions. But the research on Klotho and cancer is mainly based on animal experiments and small‐scale clinical research, thus we explored the association between serum Klotho and cancer and cancer mortality based on the National Health and Nutrition Survey (NHANES). Methods: Participants were employed from the NHANES 2007–2016, excluding pregnant, chronic renal insufficiency, and incomplete data of cancer questionnaire and serum Klotho level. The association of serum Klotho with cancer and mortality was analyzed by weighted Logistic regression, weighted Cox regression and competitive risk model, respectively. Correlations between serum Klotho and testosterone and estradiol levels were analyzed by Spearman correlation and restricted cubic spline respectively. Results: We found Klotho had an inverse effect with risk of pan‐cancer (all p < 0.02), with each unit increase in Klotho (1ug/g creatinine) associated with a 0.9%–2.2% reduction in the risk of cancer, and higher levels showing a stronger negative association (all p‐trend <= 0.0005). Whereas, we did not observe any association between serum Klotho level with all‐cause mortality and cancer‐specific mortality (all p > 0.05). Then, stratified analysis found that people aged 60–79, female, overweight and non‐Hispanic whites or Mexican Americans were less likely to develop cancer. In addition, there was a strong nonlinear and linear positive correlation of Klotho with estradiol (p‐nonlinear = 0.0178) and testosterone only among male participants (β = −0.513, p = 0.0137), respectively. Conclusions: We found an inverse association between serum Klotho and cancer, but without cancer mortality. And this effect may be partially mediated by estradiol and testosterone. Further prospective studies are needed to prove these findings. [ABSTRACT FROM AUTHOR]

In their fiscal year 2021 reports, the US House and Senate Appropriations Committees requested that the National Institutes of Health (NIH) evaluate current research related to women's health and topics that include stagnant cervical cancer survival. In response, the NIH Office of Research on Women's Health, with input from women's health experts; members of the public; representatives from NIH institutes, centers, and offices; and members of the NIH Advisory Committee on Research on Women's Health, reviewed the public health needs and current NIH activities on cervical cancer. The Advancing NIH Research on the Health of Women: A 2021 Conference held in October 2021 reviewed these findings and allowed the identification of opportunities to strengthen research. In this review, the authors summarize public health needs related to cervical cancer and NIH activities in this realm. Cervical cancer has become a rare disease in the United States, yet significant portions of the US population remain under screened or unscreened for cervical cancer, human papillomavirus vaccination rates remain low, access to high‐quality treatment remains a challenge for many, and large inequities by race and ethnicity persist. Novel, inclusive, and intentional research is needed to produce improvements in cervical cancer survival within the United States. Mortality from cervical cancer is a direct reflection of resource distribution. Future research to decrease mortality must account for systemic failures to eradicate inequities in addition to the development of novel agents against this disease. [ABSTRACT FROM AUTHOR]

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high‐density lipoprotein cholesterol (HDL‐C) predicted reduced risk of cardiovascular‐related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single‐center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow‐up period between the index PCI and latest follow‐up were 5.9 and 0‐17.8 years, respectively. Consequently, Kaplan‐Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL‐C. Multivariable Cox proportional hazard regression analysis adjusted by cancer‐related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review and meta‐analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of reporting neuroendocrine staining at diagnosis on patient outcomes. Methods: Medical databases were searched to identify studies in which adenocarcinoma specimens were stained with any of the following four neuroendocrine markers: chromogranin A (CgA), neuron‐specific enolase (NSE), synaptophysin and CD56. The prevalence of neuroendocrine staining and correlation of the prevalence of neuroendocrine staining to patient outcomes were analysed using a random‐effects model. All statistical tests were two‐sided. Results: Sixty‐two studies spanning 7616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to that of NSE (39%) and higher than that of synaptophysin (31%). The prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.49 to 2.65) and poorer prostate cancer‐specific survival (HR 7.03, 95% CI 2.55 to 19.39) compared to negative patients, even among those with low‐risk cancers. Conclusion: Discrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies are needed to determine the exact quantifiable thresholds for use in reporting neuroendocrine cell staining to identify patients at higher risk of progression. [ABSTRACT FROM AUTHOR]

Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population‐based cohorts with 271 694 participants. During a total follow‐up period of about 5.9 million person‐years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random‐effects meta‐analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02‐1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00‐1.39) and women (HR 1.44, 95% CI 1.20‐1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men. [ABSTRACT FROM AUTHOR]

The relationship between cadmium exposure, exposure‐related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd‐contaminated areas in Japan. The aim of this study was to establish the cause–effect relationship between renal tubular dysfunction and cancer mortality in the general population in non‐contaminated areas. A 19‐year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium‐non‐contaminated areas. Mortality risk ratios of urinary β2‐microglobulin (β2MG) and N‐acetyl‐β‐glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02–1.19, pancreas: HR, 1.10, 95%CI, 1.02–1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67–0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93–1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium‐non‐contaminated areas in Japan. We evaluated the relationship between renal tubular damage and cancer mortality by conducting a 19‐year cohort study in three cadmium non‐polluted areas in Japan. Mortality risk of urinary β2MG and NAG for all malignant neoplasms and specific cancers was estimated. Significant hazard ratios for liver and pancreas cancer were observed for NAG in men. [ABSTRACT FROM AUTHOR]

Background: There is extensive interest in understanding how neighborhood socioeconomic status (nSES) may affect cancer incidence or survival. However, variability regarding items included and approaches used to form a composite nSES index presents challenges in summarizing overall associations with cancer. Given recent calls for standardized measures of neighborhood sociodemographic effects in cancer disparity research, the objective of this systematic review was to identify and compare existing nSES indices studied across the cancer continuum (incidence, screening, diagnosis, treatment, survival/mortality) and summarize associations by race/ethnicity and cancer site to inform future cancer disparity studies. Methods: Using PRISMA guidelines, peer‐reviewed articles published between 2010 and 2019 containing keywords related to nSES and cancer were identified in PubMed. Results: Twenty‐four nSES indices were identified from 75 studies. In general, findings indicated a significant association between nSES and cancer outcomes (n = 64/75 studies; 85.33%), with 42/64 (65.63%) adjusting for highly‐correlated individual SES factors (e.g., education). However, the direction of association differed by cancer site, race/ethnicity, and nSES index. Conclusions: This review highlights several methodologic and conceptual issues surrounding nSES measurement and potential associations with cancer disparities. Recommendations pertaining to the selection of nSES measures are provided, which may help inform disparity‐related disease processes and improve the identification of vulnerable populations in need of intervention. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has affected cancer care worldwide. This study aimed to estimate the long‐term impacts of cancer care disruptions on cancer mortality in Canada using a microsimulation model. The model simulates cancer incidence and survival using cancer incidence, stage at diagnosis and survival data from the Canadian Cancer Registry. We modeled reported declines in cancer diagnoses and treatments recorded in provincial administrative datasets in March 2020 to June 2021. Based on the literature, we assumed that diagnostic and treatment delays lead to a 6% higher rate of cancer death per 4‐week delay. After June 2021, we assessed scenarios where cancer treatment capacity returned to prepandemic levels, or to 10% higher or lower than prepandemic levels. Results are the median predictions of 10 stochastic simulations. The model predicts that cancer care disruptions during the COVID‐19 pandemic could lead to 21 247 (2.0%) more cancer deaths in Canada in 2020 to 2030, assuming treatment capacity is recovered to 2019 prepandemic levels in 2021. This represents 355 172 life years lost expected due to pandemic‐related diagnostic and treatment delays. The largest number of expected excess cancer deaths was predicted for breast, lung and colorectal cancers, and in the provinces of Ontario, Québec and British Columbia. Diagnostic and treatment capacity in 2021 onward highly influenced the number of cancer deaths over the next decade. Cancer care disruptions during the COVID‐19 pandemic could lead to significant life loss; however, most of these could be mitigated by increasing diagnostic and treatment capacity in the short‐term to address the service backlog. [ABSTRACT FROM AUTHOR]

Background and aims: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all‐cause and cause‐specific mortality, and measure whether such associations are modified by genetic variations. Design Prospective cohort study. Setting: UK Biobank. Participants: A total of 360 937 participants aged between 37 and 73 years were enrolled in 2006–10 and ‐followed‐up to 2018. Measurements The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking‐associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all‐cause and cause‐specific mortality. Findings We identified 15 968 deaths [9022 from cancer and 5092 from cardiovascular disease (CVD)] over a median of 11.36 years' follow‐up. For all‐cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three and four were 1.23 [95% confidence intervals (CI) = 1.18–1.29), 1.66 (95% CI = 1.59–1.75), 3.33 (95% CI = 3.17–3.51) and 5.76 (95% CI = 4.66–7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45–58% reduced risk of all‐cause death compared with high PSB. Analysis of population‐attributable risk percentage indicated that 21.9, 19.1 and 24.7% of all‐cause‐, cancer‐ and CVD‐specific death could have been avoided if all ever smokers initiated smoking after age 18 years, smoked < 20 cigarettes/day and quit smoking. Conclusions: The panoramic smoking burden, based on smoking initiation, age of initiation, heaviness of smoking and smoking cessation, appears to be associated with all‐cause and cause‐specific mortality in a gradient manner with increasing panoramic smoking burden independent of other traditional and genetic risk factors. [ABSTRACT FROM AUTHOR]

Aims: We assessed the association between insulin resistance and blood glucose concentrations at type 2 diabetes diagnosis and future development of diabetes‐related complications and mortality. Materials and Methods: This retrospective cohort study included 864 individuals with type 2 diabetes (median age 60 years) whose fasting C‐peptide and HbA1c were measured at diabetes diagnosis. The median follow‐up time until death or study end was 16.4 years (interquartile range 13.3−19.6). The association between C‐peptide and mortality/complications was estimated by Cox regression adjusted for sex, age at diabetes diagnosis, smoking, hypertension, BMI, total cholesterol, and HbA1c. C‐peptide and HbA1c were converted to Z scores before the Cox regression analysis. Results: An increase by one standard deviation in fasting C‐peptide at diabetes diagnosis was associated with all‐cause (hazard ratio [HR] 1.33; 95% confidence intervals [CI] 1.12–1.58; p = 0.001) and cancer mortality (HR 1.51; 95% CI 1.13–2.01; p = 0.005) in the fully adjusted model. An increase by one standard deviation in HbA1c at diabetes diagnosis was associated with all‐cause mortality (HR 1.24; 95% CI 1.07–1.44; p = 0.005), major cardiovascular events (HR 1.20; 95% CI 1.04–1.39; p = 0.015), stroke (HR 1.36; 95% CI 1.09–1.70; p = 0.006), and retinopathy (HR 1.54; 95% CI 1.34–1.76; p < 0.0001) in the fully adjusted model. Conclusions: Fasting C‐peptide at type 2 diabetes diagnosis is an independent risk factor for total and cancer‐related mortality. Thus, treatment of type 2 diabetes should focus not only on normalising blood glucose levels but also on mitigating insulin resistance. [ABSTRACT FROM AUTHOR]

Aim: To test the association of alcohol consumption with total and cause‐specific mortality risk. Design Prospective observational multi‐centre population‐based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements Average alcohol intake by food frequency questionnaire, total and cause‐specific mortality. Findings In comparison with life‐time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high‐density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life‐time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Social determinants of health (SDOHs) cluster together and can have deleterious impacts on health outcomes. Individually, SDOHs increase the risk of cancer mortality, but their cumulative burden is not well understood. The authors sought to determine the combined effect of SDOH on cancer mortality. Methods: Using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, the authors studied 29,766 participants aged 45+ years and followed them 10+ years. Eight potential SDOHs were considered, and retained SDOHs that were associated with cancer mortality (P <.10) were retained to create a count (0, 1, 2, 3+). Cox proportional hazard models estimated associations between the SDOH count and cancer mortality through December 31, 2017, adjusting for confounders. Models were age‐stratified (45‐64 vs 65+ years). Results: Participants were followed for a median of 10.6 years (interquartile range [IQR], 6.5, 12.7 years). Low education, low income, zip code poverty, poor public health infrastructure, lack of health insurance, and social isolation were significantly associated with cancer mortality. In adjusted models, among those <65 years, compared to no SDOHs, having 1 SDOH (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.11‐1.75), 2 SDOHs (aHR, 1.61; 95% CI, 1.26‐2.07), and 3+ SDOHs (aHR, 2.09; 95% CI, 1.58‐2.75) were associated with cancer mortality (P for trend <.0001). Among individuals 65+ years, compared to no SDOH, having 1 SDOH (aHR, 1.16; 95% CI, 1.00‐1.35) and 3+ SDOHs (aHR, 1.26; 95% CI, 1.04‐1.52) was associated with cancer mortality (P for trend =.032). Conclusions: A greater number of SDOHs were significantly associated with an increased risk of cancer mortality, which persisted after adjustment for confounders. Individually, social determinants of health increase the risk of cancer mortality, but their cumulative burden is not well understood. A greater number of social determinants of health in the same individual are found to be significantly associated with an increased risk of cancer mortality, even after adjustment for a variety of confounders. [ABSTRACT FROM AUTHOR]

People with more social determinants of poor health are at higher risk for death from cancer. This article proposes a roadmap to reduce the devastating effects of social factors. [ABSTRACT FROM AUTHOR]

Tobacco smoke is a known carcinogen, but the magnitude of smoking‐related cancer risk depends on country‐specific, generational smoking patterns. We quantified cancer risk in relation to smoking in a population‐based cohort, the 45 and Up Study (2006‐2009) in New South Wales, Australia. Cox proportional hazards regressions estimated adjusted hazard ratios (HR) by self‐reported smoking history at baseline (2006‐2009) for incident, primary cancers via linkage to cancer registry data to 2013 and cancer death data to 2015. Among 229 028 participants aged ≥45 years, 18 475 cancers and 5382 cancer deaths occurred. Current‐smokers had increased risks of all cancers combined (HR = 1.42, 95% confidence interval [CI], 1.34‐1.51), cancers of the lung (HR = 17.66, 95%CI, 14.65‐21.29), larynx (HR = 11.29, 95%CI, 5.49‐23.20), head‐and‐neck (HR = 2.53, 95%CI, 1.87‐3.41), oesophagus (HR = 3.84, 95%CI, 2.33‐6.35), liver (HR = 4.07, 95%CI, 2.55‐6.51), bladder (HR = 3.08, 95%CI, 2.00‐4.73), pancreas (HR = 2.68, 95%CI, 1.93‐3.71), colorectum (HR = 1.31, 95%CI, 1.09‐1.57) and unknown primary site (HR = 3.26, 95%CI, 2.19‐4.84) versus never‐smokers. Hazards increased with increasing smoking intensity; compared to never‐smokers, lung cancer HR = 9.22 (95%CI, 5.14‐16.55) for 1‐5 cigarettes/day and 38.61 (95%CI, 25.65‐58.13) for >35 cigarettes/day. Lung cancer risk was lower with quitting at any age but remained higher than never‐smokers for quitters aged >25y. By age 80y, an estimated 48.3% of current‐smokers (41.1% never‐smokers) will develop cancer, and 14% will develop lung cancer, including 7.7% currently smoking 1‐5 cigarettes/day and 26.4% for >35 cigarettes/day (1.0% never‐smokers). Cancer risk for Australian smokers is significant, even for 'light' smokers. These contemporary estimates underpin the need for continued investment in strategies to prevent smoking uptake and facilitate cessation, which remain key to reducing cancer morbidity and mortality worldwide. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have suggested that fasting plasma glucose (FPG) was associated with the risk of mortality. However, relationship on longitudinal changes of FPG with the risk of mortality remained inconsistent. Methods: We examined the association of FPG at baseline and its longitudinal changes with risk of mortality based on a cohort study in Yinzhou, China, during 2010–2018. Cox regression models and competing risk models were separately used to examine the association of FPG levels and long‐term fluctuation with risk of total and cause‐specific mortality. Results: Subjects who had an impaired fasting glucose or diabetes suffered a higher risk of total mortality than subjects who had a normal fasting glucose (HRs and 95% CIs: 1.17 [1.01–1.35], 1.30 [1.10–1.53], respectively). The HR for total mortality was 1.54 (95% CI: 1.29–1.84) and for cancer mortality was 1.41 (95% CI: 1.04–1.92) in the highest quartile of coefficient of variation of FPG. Trajectory analysis indicated that subjects with a significantly changed FPG suffered a higher risk of total mortality. Conclusion: According to this cohort study, we found that long‐term fluctuation of FPG was significantly associated with the risk of total and cancer mortality. Our findings suggest that long‐term fluctuation of FPG could be used as an efficient indicator for predicting the subsequent risk of mortality. [ABSTRACT FROM AUTHOR]

Recent meta‐analyses of randomized controlled trials (RCTs) have demonstrated significant reduction in cancer mortality by vitamin D supplementation. We estimated costs and savings for preventing cancer deaths by vitamin D supplementation of the population aged 50+ years in Germany. Our analysis is based on national data on cancer mortality in 2016. The number of preventable cancer deaths was estimated by multiplying cancer deaths above age 50 with the estimated proportionate reduction in cancer mortality derived by vitamin D supplementation according to meta‐analyses of RCTs (13%). Saved costs were estimated by multiplying this number by estimated end‐of‐life cancer care costs (€40 000). Annual costs of vitamin D supplementation were estimated at 25€ per person above age 50. Comprehensive sensitivity analyses were conducted. In the main analysis, vitamin D supplementation was estimated to prevent almost 30 000 cancer deaths per year at approximate costs of €900 million and savings of €1.154 billion, suggesting net savings of €254 million. Our results support promotion of supplementation of vitamin D among older adults as a cost‐saving approach to substantially reduce cancer mortality. [ABSTRACT FROM AUTHOR]

The relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta‐analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta‐analyses. For meta‐analyses of trials, we assessed their quality using AMSTAR‐2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) criteria. Meta‐analyses of observational studies reported inverse associations of 25OHD with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford‐Hill's causation criteria. In meta‐analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with five out of six meta‐analyses reporting a relative risk (RR) reduction of up to 16%: RR, 0.84 (95% CI, 0.74–0.95). The strength of the association, however, was classified as weak. This was true among meta‐analyses of high, moderate, and lower quality (AMSTAR‐2–rated). Trials did not include large numbers of vitamin D‐deficient participants; many tested relatively low doses and lacked sufficiently powered data on site‐specific cancers. In conclusion, meta‐analyses show that, although observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials show that vitamin D supplementation reduces total cancer mortality, but not cancer incidence. However, trials with larger proportions of vitamin D‐insufficient participants and longer durations of follow‐up, plus adequately powered data on site‐specific common cancers, would provide further insight into the evidence base. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Economic and living conditions have improved over time in most countries, although often in association with detrimental lifestyle and environmental changes that are major determinants of cancer. In this ecological study, we assess the association between national socioeconomic levels and incidence and mortality rates for all cancers combined and 27 cancer types, in 175 countries. We obtained national level cancer incidence and mortality estimates for 2018 from GLOBOCAN and computed an index of socioeconomic development based on national education and income levels extracted from the United Nations Development Programme. Cancer incidence rates are strongly positively associated with the national socioeconomic level for all cancers combined and for a large number of cancer types, in both sexes. Conversely, the association between socioeconomic development and cancer mortality rates is less clear. The most common pattern for type‐specific cancers is an increasing incidence rate with a relatively stable mortality rate as socioeconomic development increases. Despite the high incidence rates for many cancer types, mortality rates are relatively low in high‐income countries, partly due to the availability of early detection and effective treatments. As socioeconomic development continues to rise, countries with currently low‐ and medium‐development levels may experience large increases in the incidence of several cancers. Given the limited resources and lack of infrastructure, increases in incidence rates in low‐income countries will likely be paralleled by increases in mortality rates. Efforts to plan, implement and evaluate prevention programs must therefore be considered as greater priorities in Low‐ and Middle‐income countries. What's new? Socioeconomic development is often associated with detrimental lifestyle changes and environmental exposures that are major determinants of cancer. Here, the authors assess for the first time the association between national socioeconomic level and incidence and mortality rates for all cancers combined and for 27 cancer types in 175 countries. As socioeconomic development continues to grow, low‐ and medium‐income countries may face high cancer incidence rates as already experienced by high‐income countries. However, higher cancer mortality rates are likely to ensue given the limited resources and lack of infrastructure. The findings advocate for efforts to plan healthcare resources and preventive measures. [ABSTRACT FROM AUTHOR]

The potential of physical activity (PA) to attenuate the effects of alcohol consumption on the risks of alcohol‐related cancer mortality is unknown. We used data from participants aged 30 years and over in 10 British population‐based surveys (Health Surveys for England 1994, 1997, 1998, 1999, 2003, 2004, 2006 and 2008 and the Scottish Health Surveys 1998 and 2003). Alcohol‐related cancer mortality included oral cavity, throat, larynx, oesophagus, liver, colorectal, stomach and female breast (conservative definition), and additionally pancreas and lung (broad definition). Alcohol consumption was categorised into six groups based on the UK units/week: (a) never‐drinkers, (b) ex‐drinkers, (c) occasional drinkers, (d) within guidelines (<14 UK units/week [women]; <21 UK units/week [men]), (e) hazardous (14‐35 [women]; 21‐49 [men]) and (f) harmful (>35 [women]; >49 [men]). PA was categorised using two dichotomous classifications based on the lower (7.5 Metabolic Equivalent Task [MET]‐hours/week) and upper (15 MET‐hours/week) recommended limits. Using Cox proportional hazard models, we found a strong direct association between alcohol consumption and mortality risk of alcohol‐related cancers, with a significantly higher risk among ex‐drinkers (Hazard ratio [HR] = 1.46, 95% confidence interval [CI] = [1.09, 1.94]), drinkers who consumed hazardous (HR = 1.39, 95% CI = [1.06, 1.83]) and harmful amounts of alcohol (HR = 1.62, 95% CI = [1.13, 2.30]) compared to never‐drinkers in the fully adjusted model. The increased mortality risks were substantially attenuated when participants in these drinking groups exercised >7.5 MET‐hours/week. PA could be promoted as an adjunct risk minimisation measure for alcohol‐related cancer prevention. What's new? While alcohol consumption contributes to cancer mortality and is pervasive worldwide, many people who drink also engage in physical activity, which has numerous health benefits. The combined impact of these behaviors on cancer mortality risk is unknown. Here, alcohol consumption was strongly associated with alcohol‐related cancer mortality risk among participants from 10 British population‐based studies. This risk, however, was significantly reduced in physically active participants who met at least the lower recommended limit of activity per week. The findings suggest that adopting physical activity as a healthy lifestyle behavior could lessen the impact of alcohol consumption on cancer mortality. [ABSTRACT FROM AUTHOR]

Socioeconomic inequalities in cancer mortality have been described for a range of cancers sites worldwide, using diverse measures of socioeconomic position (SEP). These studies have shown a negative social gradient where lower SEP was associated with greater odds of having cancer, particularly in men. However, there is a lack of information regarding low and middle‐income countries. The objective of our study was to analyze the relationship between the socioeconomic characteristics of patients' residential districts and mortality due to cancer in Costa Rica between 2011 and 2017. An ecological study at the level of the district of residence was conducted using the multilevel mixed‐effects Poisson regression. All cancer‐caused deaths between January 1, 2011 and December 31, 2017 were included (n = 32,117). Eleven cancer sites were analyzed independently. The 477 Costa Rican districts were divided by area (urban/mixed/rural) and wealth using census data. All‐cancer combined a significant association between cancer mortality and wealth was found. Cancer mortality was lower in the poorest as compared to the richest districts (IRRQ4 = 0.79 [0.73–0.86]). The majority of cancer sites followed a similar pattern, showing a positive social gradient. These results contradict the international literature mostly conducted in high‐income countries. These findings confirmed the importance of conducting studies in middle‐income countries, since the socioeconomic and cultural contexts are different from those in high‐income countries, which influence the social distribution of lifestyles and risk behaviors. What's new? While socioeconomic position (SEP) and cancer mortality are closely associated worldwide, where lower socioeconomic position was associated with greater odds of having cancer, all‐cancer combined. In this investigation of population‐based national registries specifically in Costa Rica, cancer mortality was found to follow a positive social gradient for the majority of cancer sites analyzed. The more socioeconomically deprived a district, the lower its cancer mortality. These findings are not consistent with international literature on SEP and cancer mortality and confirm the importance of conducting studies in middle‐income countries. [ABSTRACT FROM AUTHOR]

Purpose: Thyroid cancer incidence is rising, possibly secondary to increased imaging and surveillance. Based on rural access to care disparities, we hypothesized that incidence would be greater in urban compared to rural counties with no significant difference in long‐term survival. Methods: An observational study was performed on thyroid cancer patients using Surveillance Epidemiology and End Results data (2000‐2012). Age‐adjusted incidence rates, incidence rate ratios, and survival rates were calculated across rural‐urban designations. Findings: Incidence rates were 11.2, 9.8, and 10.1 per 100,000 for urban, rural‐adjacent, and rural‐nonadjacent counties, respectively. Statistically significantly lower incidence was noted in rural‐adjacent and rural‐nonadjacent compared to urban areas. Five‐year and 10‐year survival was significantly lower in rural‐nonadjacent counties compared to urban counties. Conclusions: Higher incidence and increased long‐term survival for thyroid cancer were noted in urban areas compared to rural areas. It is uncertain if rural‐urban differences in long‐term survival reflect health care disparities, differences in therapy, or other origins. [ABSTRACT FROM AUTHOR]

Background: Cancer contributes substantially to the life expectancy gap between US blacks and whites, and racial cancer disparities remain stubborn to eradicate. Disparities vary geographically, suggesting that they are not inevitable.Methods: The authors examined the relationship between housing discrimination and the size of cancer disparities across large US metropolitan statistical areas (MSAs). MSA-level cancer disparities were measured using data from the US Centers for Disease Control and Prevention. Mortgage discrimination for each MSA was estimated using the Home Mortgage Disclosure Act database, and MSA racial segregation was determined using US Census data. Patterns of housing discrimination and cancer disparities were mapped, and the associations between these place-based factors and cancer disparities across MSAs were measured.Results: Black-to-white cancer mortality disparities (rate ratios) varied geographically, ranging from 1.50 to 0.86; 88% of mortality ratios were >1, indicating higher mortality for blacks. In areas with greater mortgage discrimination, the gap between black and white cancer mortality rates was larger (correlation coefficient [r] = 0.32; P = .001). This relationship persisted in sex-specific analyses (males, r = 0.37; P < .001; females, r = 0.23; P = .02) and in models controlling for confounders. In contrast, segregation was inconsistently associated with disparities. Adjusting for incidence disparities attenuated, but did not eliminate, the correlation between mortgage discrimination and mortality disparities (r = 0.22-0.24), suggesting that cancer incidence and survival each account for part of the mortality disparity.Conclusions: Mortgage discrimination is associated with larger black-to-white cancer mortality disparities. Some areas are exceptions to this trend. Examination of these exceptions and of policies related to housing discrimination may offer novel strategies for explaining and eliminating cancer disparities. [ABSTRACT FROM AUTHOR]

Background: Surveillance recommendations for patients with low-risk, non-muscle-invasive bladder cancer (NMIBC) are based on limited evidence. The objective of this study was to add to the evidence by assessing outcomes after frequent versus recommended cystoscopic surveillance.Methods: This was a retrospective cohort study of patients diagnosed with low-risk (low-grade Ta (AJCC)) NMIBC from 2005 to 2011 with follow-up through 2014 from the Department of Veterans Affairs. Patients were classified as having undergone frequent versus recommended cystoscopic surveillance (>3 vs 1-3 cystoscopies in the first 2 years after diagnosis). By using propensity score-adjusted models, the authors estimated the impact of frequent cystoscopy on the number of transurethral resections, the number of resections without cancer in the specimen, and the risk of progression to muscle-invasive cancer or bladder cancer death.Results: Among 1042 patients, 798 (77%) had more frequent cystoscopy than recommended. In adjusted analyses, the frequent cystoscopy group had twice as many transurethral resections (55 vs 26 per 100 person-years; P < .001) and more than 3 times as many resections without cancer in the specimen (5.7 vs 1.6 per 100 person-years; P < .001). Frequent cystoscopy was not associated with time to progression or bladder cancer death (3% at 5 years in both groups; P = .990).Conclusions: Frequent cystoscopy among patients with low-risk NMIBC was associated with twice as many transurethral resections and did not decrease the risk for bladder cancer progression or death, supporting current guidelines. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that lower socioeconomic status (SES) was associated with higher all‐cause mortality in patients newly diagnosed with cancer, particularly in the elderly population. Methods: We collected study patients from the stratified random sample of Korean National Health Insurance Elderly Cohort (2002‐2015). The Cox's proportional hazards model was used to investigate the risk factors for mortality. Income level and composite deprivation index (CDI) 2010 were used to define the SES: low, intermediate, and high SES groups. The comorbidities were measured using Charlson Comorbidity Index score. After a wash‐out period (2002), the final study population was 108 626 (2003‐2015). Results: In multivariate analysis, low SES was associated with poor overall survival (OS) (HR = 1.08, 95% CI: 1.05‐1.12, P < 0.001) and cancer‐specific survival (CSS) (HR = 1.11, 95% CI: 1.06‐1.16, P < 0.001) particularly for patients aged 70‐79 years. High SES was favorable prognostic factor of OS in patients aged 60‐69 years (HR = 0.85, 95% CI: 0.81‐0.89, P < 0.001), 70‐79 years (HR = 0.90, 95% CI: 0.87‐0.93, P < 0.001), and ≥80 years (HR = 0.91, 95% CI: 0.87‐0.96, P < 0.001). However, SES was not associated with CSS in advanced age patients (≥80 years). Patients with low SES manifesting colorectal, urinary, liver, gastric, melanoma, and esophageal cancers demonstrated worse OS, compared to patients with intermediate SES. Also, low SES patients with urinary, liver, or colorectal cancers or melanoma demonstrated worse CSS compared to those with intermediate SES. Conclusion: Low SES at the time of cancer diagnosis is associated with increased risk of OS and CSS in elderly patients. Depending on cancer sites, different patterns of OS and CSS were observed according to SES. Further elucidation of the causes underlying these phenomena is needed along with appropriate support for elderly cancer patients with low SES. [ABSTRACT FROM AUTHOR]

Breast cancer is a major cause of cancer mortality. Regarding the advantages of polymeric nanoparticles as drug delivery systems with targeting potential, in this study the antitumor mechanism of targeted docetaxel polymeric nanoparticles of Ecoflex® was exploited. Since the overexpression of HER‐2 receptor in breast cancer cases is associated with poor prognosis and more aggressive disease, the proposed nanoparticles were conjugated to HER‐2 specific aptamer molecules. In vitro cytotoxicity was evaluated by MTT assay. Flow‐cytometry analysis was performed to evaluate the cellular uptake of nanoparticles loaded with a fluorescent probe. Anti‐migration effects of samples were studied. Annexin IV‐FITC and propidium iodide were implemented to investigate apoptosis induction and cell cycle analysis. Enhanced cytotoxicity compared with free docetaxel was explained considering improved cellular uptake of the nanoparticles and induced apoptosis in a larger portion of cells. Lower relative migration demonstrated enhanced anti‐migration effect of nanoparticles, and cell cycle was arrested in G2/M phase using both formulations so the anti‐microtubule mechanism of the drug was not altered. Therefore, this system could offer a potential substitute for the currently marketed docetaxel formulations, which may reduce adverse effects of the drug, while further in vivo and clinical investigations are required. [ABSTRACT FROM AUTHOR]

The relative concentration index (RCI) and the absolute concentration index (ACI) have been widely used for monitoring health disparities with ranked health determinants. The RCI has been extended to allow value judgments about inequality aversion by Pereira in 1998 and by Wagstaff in 2002. Previous studies of the extended RCI have focused on survey sample data. This paper adapts the extended RCI for use with directly standardized rates (DSRs) calculated from population-based surveillance data. A Taylor series linearization (TL)-based variance estimator is developed and evaluated using simulations. A simulation-based Monte Carlo (MC) variance estimator is also evaluated as a comparison. Following Wagstaff's approach in 1991, we extend the ACI for use with DSRs. In all simulations, both the TL and MC methods produce valid variance estimates. The TL variance estimator has a simple, closed form that is attractive to users without sophisticated programming skills. The TL and MC estimators have been incorporated into a beta version of the National Cancer Institute's Health Disparities Calculator, a free statistical software tool that enables the estimation of 11 commonly used summary measures of health disparities for DSRs. [ABSTRACT FROM AUTHOR]

Background: There is evidence that low‐level alcohol use, drinking 1 to 2 drinks on occasion, is protective for cardiovascular disease, but increases the risk of cancer. Synthesizing the overall impact of low‐level alcohol use on health is therefore complex. The objective of this paper was to examine the association between frequency of low‐level drinking and mortality. Methods: Two data sets with self‐reported alcohol use and mortality follow‐up were analyzed: 340,668 individuals from the National Health Interview Survey (NHIS) and 93,653 individuals from the Veterans Health Administration (VA) outpatient medical records. Survival analyses were conducted to evaluate the association between low‐level drinking frequency and mortality. Results: The minimum risk drinking frequency among those who drink 1 to 2 drinks per occasion was found to be 3.2 times weekly in the NHIS data, based on a continuous measure of drinking frequency, and 2 to 3 times weekly in the VA data. Relative to these individuals with minimum risk, individuals who drink 7 times weekly had an adjusted hazard ratio (HR) of all‐cause mortality of 1.23 (p < 0.0001) in the NHIS data, and individuals who drink 4 to 7 times weekly in the VA data also had an adjusted HR of 1.23 (p = 0.01). Secondary analyses in the NHIS data showed that the minimum risk was drinking 4 times weekly for cardiovascular mortality, and drinking monthly or less for cancer mortality. The associations were consistent in stratified analyses of men, women, and never smokers. Conclusions: The minimum risk of low‐level drinking frequency for all‐cause mortality appears to be approximately 3 occasions weekly. The robustness of this finding is highlighted in 2 distinctly different data sets: a large epidemiological data set and a data set of veterans sampled from an outpatient clinic. Daily drinking, even at low levels, is detrimental to one's health. This study evaluated the association between mortality and frequency of light drinking (1–2 drinks). In both an epidemiological dataset (NHIS) and a clinical outpatient dataset (VA), we found increased risk of all‐cause mortality among those who drank 4 or more times weekly relative to those who drank less frequently. This suggests that frequent low‐level drinking increases mortality. [ABSTRACT FROM AUTHOR]

Abstract: Context: Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied. Design and Participants: The Three‐City cohort study included (1999‐2001) 3650 men ≥65 years who were followed for mortality over 12 years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms. Main Outcome: Mortality data were obtained from death certificates. We used inverse probability weighted Cox models to examine the association of oestradiol with all‐cause and cause‐specific mortality and its interaction with ER genetic polymorphisms. Results: A total of 183 men died over the follow‐up (cardiovascular disease (CVD), n = 44; cancer, n = 57; other causes, n = 82). After adjustment, there was a quadratic relationship of all‐cause mortality with tE2 and fE2 (P‐quadratic = 0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P‐quadratic = 0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all‐cause mortality. Conclusion: In elderly men, we showed a nonlinear association of tE2 and fE2 with all‐cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association. [ABSTRACT FROM AUTHOR]

Background/objectives: The Oslo diet and antismoking study showed that counselling for a healthy lifestyle reduced lifelong coronary mortality in high-risk men. We explored whether the same counselling reduced also cancer risk.Methods: The study randomly allocated males at high coronary risk to either a 5-year intervention for lifestyle changes (cholesterol-lowering dietary changes, weight loss and stopping smoking) or a control group (1 : 1) in 1972/73. We explored the incidence and mortality of all cancers and cancer forms related to smoking, BMI or diet up to 43 years after randomization.Results: A total of 595 men in the intervention and 621 in the control group were included. At inclusion median age was 45 years, 588 (48.4%) subjects were overweight (BMI > 25 kg m-2 ) and 925 (76.1%) current smokers. The intervention did not reduce the risk of cancer after 43 years (adjusted hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.80-1.15). In the first 25 years of follow-up, among the 1088 (89.5%) men who were overweight/obese and/or smokers, the intervention reduced the incidence of those cancer forms related to smoking, BMI or diet (including carcinoma of the respiratory, digestive and urinary tracts; adjusted HR 0.69; 95% CI 0.49-0.99). The intervention had no significant effect on incidence beyond 25 years, or on mortality.Conclusions: The 5-year counselling for a healthy lifestyle did not reduce the overall cancer risk in the very long term. However, in the first 25 years, the counselling reduced the risk of relevant cancer types in overweight/obese subjects and smokers. [ABSTRACT FROM AUTHOR]

This article summarizes cancer mortality trends and disparities based on data from the National Center for Health Statistics. It is the first in a series of articles that will describe the American Cancer Society's vision for how cancer prevention, early detection, and treatment can be transformed to lower the cancer burden in the United States, and sets the stage for a national cancer control plan, or blueprint, for the American Cancer Society goals for reducing cancer mortality by the year 2035. Although steady progress in reducing cancer mortality has been made over the past few decades, it is clear that much more could, and should, be done to save lives through the comprehensive application of currently available evidence-based public health and clinical interventions to all segments of the population. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The specific role of different strength measures on mortality risk needs to be clarified to gain a better understanding of the clinical importance of different muscle groups, as well as to inform intervention protocols in relation to reducing early mortality. The aim of the systematic review and meta‐analysis was to determine the relationship between muscular strength and risk of cancer mortality. Eligible cohort studies were those that examined the association between muscular strength, as assessed using validated tests, and cancer mortality in healthy youth and adults. The hazard ratio (HR) estimates obtained were pooled using random effects meta‐analysis models. The outcome was cancer mortality assessed using the HR (Cox proportional hazards model). Eleven prospective studies with 1 309 413 participants were included, and 9787 cancer‐specific deaths were reported. Overall, greater handgrip (HR = 0.97, 95% CI, 0.92‐1.02; P = .055; I2 = 18.9%) and knee extension strength (HR = 0.98, 95% CI, 0.95‐1.00; P = .051; I2 = 60.6%) were barely significant associated with reduced risk of cancer mortality. Our study suggests that higher level of muscular strength is not statistically associated with lower risk of cancer mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Objective: Insulin‐like growth factor 1 (IGF1) has anabolic and growth‐promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF1 is bound to binding proteins, which modulate bioavailability of IGF1. This study assessed the associations of IGF1 and its binding proteins 1 (IGFBP1) and 3 (IGFBP3) with cancer risk. Design: A prospective cohort study of 4042 men aged ≥70 years. Methods: Plasma total IGF1, IGFBP1 and IGFBP3 were measured between 2001 and 2004. Cancer‐related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios (SHR). Results: There were 907 men who were diagnosed with cancer during a median of 9‐year follow‐up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully‑adjusted model, higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR = 1.20, 95% CI 1.01‐1.43; P = .041 for every 1 standard deviation increase in IGFBP3) but not other cancers. This effect was not attenuated by inclusion of total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03‐1.58; P = .025). Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer‐related deaths. Conclusion: Higher IGFBP3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF1. Further studies are warranted to explore potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

Proinflammatory dietary patterns have been associated with increased cancer risk and mortality. We present a systematic review and meta-analysis of the current published literature on a dietary inflammatory index (DII) score and its association with cancer risk and mortality outcomes. Published articles from online databases (PubMed, Scopus, and Embase) examining the association between DII and any cancer risk, incidence, or mortality between 1980 and November 2016 were selected for review. Results of studies meeting inclusion criteria were summarized and meta-analyzed using STATA to generate summary measures of association across studies. Sixty-three published articles were identified from the search, and following title, abstract and full-text review, twenty-four studies met inclusion criteria. All articles calculated DII scores based on study-specific food-frequency questionnaires using methodology from the same article. Of the 24 included studies, 13 were case-control, 6 were prospective cohort, 1 was a retrospective cohort, 3 were RCTs, and 1 did not specify study design. The most common cancers examined were colorectal, breast, lung, and prostate. Individuals in the highest versus lowest DII categories had 25% increased risk of overall cancer incidence (RR: 1.25, 95% CI: 1.16-1.35), 75% higher odds of cancer (OR: 1.75, 95% CI: 1.43-2.16) and 67% increased risk of cancer mortality (RR: 1.67, 95% CI: 1.13-2.48). Upon stratification for cancer type, positive associations remained (RRbreast: RR: 1.12, 95% CI: 1.03-1.22) (RRcolorectal: 1.33, 95% CI: 1.22-1.46) (RRlung: 1.30, 95% CI: 1.13-1.50). There were consistent and significant positive associations between higher DII and cancer incidence and mortality across cancer types, study populations, and study design. [ABSTRACT FROM AUTHOR]

The preventive effect of coffee on cancer at different sites has been reported, but the effect on all-sites cancer incidence has not been extensively investigated. We evaluated the association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality among 39 685 men and 43 124 women (age 40-79 years, at baseline), in the Three-Prefecture Cohort Study. The association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality was assessed by a Cox proportional hazards regression model, adjusted for potential confounders. During 411 341 person-years among men and 472 433 person-years among women, a total of 4244 men and 2601 women developed cancer at different sites and a total of 3021 men and 1635 women died of cancer at different sites. We showed an inverse association between frequency of coffee consumption and all-sites cancer incidence in both men and women. Comparing participants who consumed coffee with those who never drank coffee, the adjusted hazard ratios (95% confidential interval) for all-sites cancer incidence was 0.74 (0.62-0.88) for coffee consumption of ≥5 cups/day in men ( P for trend < 0.001) and 0.76 (0.58-1.02) in women ( P for trend = 0.020). Coffee consumption frequency was inversely associated with mortality from all-sites cancer. In this population, increasing coffee consumption resulted in a decreased risk of all-sites cancer incidence and mortality. [ABSTRACT FROM AUTHOR]