An assessment of progress in cancer control.

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.

Short-term ozone exposure and cancer mortality in Brazil: A nationwide case-crossover study.

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short-term O3 exposure and site-specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time-stratified case-crossover design was applied to assess the O3-cancer mortality association. Subgroup analyses by age, sex, season, time-period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non-threshold exposure-response relationship was observed for short-term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%-1.20%) increase in all-cancer mortality risks for each 10-µg/m3 increment of three-day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000-2019, a total of 147,074 (116,690-177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014-28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations.

Cancer mortality after kidney transplantation: A multicenter cohort study in Italy.

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.

Human-mouse comparison of the multistage nature of radiation carcinogenesis in a mathematical model.

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.

The association between neighborhood-level income and cancer stage at diagnosis and survival in Alberta.

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.

Living alone and cancer mortality by race/ethnicity and socioeconomic status among US working-age adults.

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.

Breast Cancer Risk Assessment Tool (BCRAT) and long-term breast cancer mortality in the Women's Health Initiative.

BACKGROUND: While the Breast Cancer Risk Assessment Tool (BCRAT) predicts breast cancer incidence, the model's performance, re-purposed to predict breast cancer mortality, is uncertain. Therefore, we examined whether the BCRAT model predicts breast cancer mortality in postmenopausal women in the Women's Health Initiative (WHI). METHODS: BCRAT 5-year breast cancer incidence risk estimates were calculated for 145,408 women (aged 50-79 years) enrolled in the WHI at 40 US clinical centers to examine associations of BCRAT risk groups (< 1%, 1-< 3%, ≥ 3%) with breast cancer mortality using Cox proportional regression modeling in all participants and in those with incident breast cancer. RESULTS: Women with BCRAT ≥ 3% risk, compared to women with BCRAT < 1% risk, were older (age 70-79 years: 38.3% versus 5.3%), less commonly Black (1.1% versus 40.2%), and had stronger breast cancer family history. With 20-years follow-up, considering all participants, with 8,849 breast cancers and 1,076 breast cancer deaths, breast cancer mortality in BCRAT group ≥ 3% was not higher versus BCRAT group < 1% (Hazard Ratio [HR] 1.06 95% Confidence Interval [CI] 0.80-1.40): percent without 20-year breast cancer mortality; 99.4% [group < 1%] and 98.8% [group ≥ 3%]. Considering women with incident breast cancer, breast cancer mortality was also not higher in BCRAT group ≥ 3% versus BCRAT group < 1% (HR 1.07 95% CI 0.79-1.45). CONCLUSIONS: The BCRAT model, at ≥ 3% 5-year incidence risk (US guideline threshold for chemoprevention), does not identify women with higher breast cancer mortality risk, with implications for breast cancer prevention strategies.

Association of weight change with all-cause and cause-specific mortality: an age-stratified analysis.

BACKGROUND: The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified (< 65 vs ≥ 65 years) associations of weight change with all-cause and cause-specific mortality in a large sample of Chinese adults. METHODS: Our cohort study included 746,991 adults aged at least 45 years from the Shenzhen Healthcare Big Data Cohort in China. BMI change were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by > 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders. RESULTS: During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54-1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52-1.84), CVD mortality (HR: 1.55, 95% CI: 1.34-1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33-1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04-1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04-1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12-1.44). For participants < 65 years, only more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.41, 95% CI: 1.12-1.77), non-communicable disease mortality (HR: 1.43, 95% CI: 1.13-1.81), and cancer mortality (HR: 1.79, 95% CI: 1.29-2.47). CONCLUSIONS: Weight loss and excessive weight gain were associated with increased risks of mortality among older adults, while only excessive weight loss was associated with increased risks of mortality among middle-aged adults.

Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

PURPOSE: There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. METHODS: In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years of smoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. RESULTS: A sample of 817 patients with breast cancer were followed for a median of 18.7 years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. CONCLUSION: Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Association between hypertension grades and cancer mortality among Japanese men and women.

PURPOSE: We aimed to examine the association between hypertension grades and the risk of total and site-specific cancer mortality among Japanese men and women. METHODS: In the Japan Collaborative Cohort Study, 27,332 participants aged 40-79 years were enrolled and followed up with their mortality until 2009. According to the measured blood pressure (BP) at baseline, we classified the participants into four BP categories based on 2018 European guidelines. The Cox proportional hazard models were used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of total and site-specific cancer mortality according to the hypertension category. RESULTS: During the 18.5 years of median follow-up, 1,927 cancer deaths were documented. Grade 1 (systolic blood pressure [SBP] 140-159 mmHg or diastolic blood pressure [DBP] 90-99 mmHg) and grade 2-3 hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) were associated with an increased risk of total cancer mortality; the multivariable HRs were 1.17 (1.04-1.32) for grade 1, and 1.27 (1.09-1.47) for grade 2-3 hypertension compared to optimal and normal BP (SBP < 130 mmHg and DBP < 85 mmHg). Linear and positive associations were observed between SBP and DBP 10 mmHg increment and the risk of total cancer mortality; HRs were 1.06 (1.03-1.08) for SBP and 1.07 (1.02-1.11) for DBP of 10 mmHg increment. The excess risk was primarily found for esophageal, liver, and pancreatic cancer; the respective multivariable HRs of grade 2-3 hypertension vs optimal and normal BP were 2.57 (1.10-6.04) for esophageal, 1.67 (1.01-2.77) for liver, and 1.95 (1.17-3.23) for pancreatic cancer. CONCLUSION: Hypertension was associated with the increased risk of total cancer mortality, primarily of esophageal, liver, and pancreatic cancer.

Sleep and cancer mortality in the Cancer Prevention Study-II.

PURPOSE: Sleep is a multi-dimensional human function that is associated with cancer outcomes. Previous work on sleep and cancer mortality have not investigated how this relationship varies by sex and cancer site. We investigated the association of sleep duration and perceived insomnia with site-specific and overall cancer mortality among participants in the Cancer Prevention Study-II. METHODS: Sleep was collected at baseline in 1982 among 1.2 million cancer-free US adults. Cancer-specific mortality was determined through 2018. We used multivariable Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality, stratified by sex. RESULTS: Among 983,105 participants (56% female) followed for a median of 27.9 person-years, there were 146,911 primary cancer deaths. Results from the adjusted model showed short (6 h/night) and long (8 h/night and 9-14 h/night) sleep duration, compared to 7 h/night, were associated with a modest 2%, 2%, and 5% higher risk of overall cancer mortality, respectively, and there was a significant non-linear trend (p-trend < 0.01). This non-linear trend was statistically significant among male (p-trend < 0.001) but not female (p-trend 0.71) participants. For male participants, short and long sleep were associated with higher risk of lung cancer mortality and long sleep was associated with higher risk of colorectal cancer mortality. Perceived insomnia was associated with a 3-7% lower risk of overall cancer mortality. CONCLUSION: Sleep is important to consider in relation to sex- and site-specific cancer mortality. Future research should investigate other components of sleep in relation to cancer mortality.

Avoiding lead-time bias by estimating stage-specific proportions of cancer and non-cancer deaths.

PURPOSE: Understanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening. METHODS: Using data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50-84 years at cancer diagnosis in 2006-2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020. RESULTS: Most cancer patients diagnosed at stages I-II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I-II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I-II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach. CONCLUSION: Across all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I-II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened.

Trends in papillary thyroid cancer mortality in Denmark according to stage and education.

OBJECTIVE: Few studies exist on trends in papillary thyroid cancer (PTC) survival and mortality according to stage and level of socioeconomic status. DESIGN: Nationwide cohort study. PATIENTS AND MEASUREMENTS: Patients diagnosed with PTC during 2000-2015 in Denmark were identified from the Danish Cancer Registry and followed until the end of 2020. We evaluated 5-year all-cause mortality and relative survival according to stage and 5-year mortality rates with corresponding average annual percentage changes (AAPCs) according to stage and education. Finally, we assessed the association between several factors and mortality of PTC using Cox regression. RESULTS: For the 2006 cases of PTC diagnosed during 2000-2015, relative survival tended to increase and mortality rates tended to decrease for all stages. For localized PTC, mortality rates tended to decrease among individuals with medium education (AAPC = -7.0, 95% confidence interval [CI]: -14.7 to 1.5), but showed an increasing pattern among individuals with long education (AAPC = 19.8, 95% CI: -4.2 to 50.0). For nonlocalized PTC, mortality rates showed a decreasing tendency among individuals with medium and long education (AAPC = -5.5, 95% CI: -13.2 to 2.9, and AAPC = -10.4, 95% CI: -20.8 to 1.4, respectively). Being diagnosed with PTC in a more recent calendar period and long education were associated with a lower mortality rate in the Cox regression analysis. CONCLUSIONS: A pattern of an increasing relative survival and decreasing mortality rates of PTC across all stages was seen in Denmark during 2000-2015. The decreasing pattern in mortality rates was most evident in individuals with localized stage and medium education, and in individuals with nonlocalized stage and medium or long education.

Opportunistic prostate-specific antigen testing in Norwegian men: a public health challenge.

OBJECTIVE: To describe age-specific prostate-specific antigen (PSA) distributions and resulting prostate cancer diagnoses that arise from population-wide opportunistic PSA testing. PATIENTS AND METHODS: Over 8 million PSA tests were performed on >1.4 million Norwegian men from 2000 to 2020. During this period 43 486 men were diagnosed with localised prostate cancer. Most of the PSA testing reflected opportunistic testing. Age-specific PSA value distributions were constructed for men aged 45-75 years with and without prostate cancer. RESULTS: The distributions of PSA values in men with and without prostate cancer widened with age and overlapped extensively from 3 to 7 ng/mL. Localised prostate cancer diagnoses increased 10-fold from the age of 45 to 75 years. PSA testing identified intermediate- or high-grade cancers in 21% (95% confidence interval [CI] 19-23%) of men aged 50-54 years and 42% (95% CI 41-43%) of men aged 70-74 years. Grade group (GG)1, GG2, GG3 and ≥GG4 constituted 49%, 31%, 10% and 10% of cancers identified at age 50-54 years and 26%, 26%, 18%, and 30% of cancers identified at age 70-74 years. CONCLUSION: Opportunistic PSA testing increases with ageing and often generates values that cannot discriminate benign prostate enlargement from prostate cancer. A clinical cascade using additional imaging or serum tests is necessary to avoid negative biopsies and the overdiagnosis of indolent disease. The declining specificity of PSA testing with ageing poses a significant public health challenge especially among older men aged ≥70 years.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

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.

Association of metabolic score for visceral fat with all-cause mortality, cardiovascular mortality, and cancer mortality: A prospective cohort study.

AIM: Our study aimed to evaluate the association between the metabolic score for visceral fat (METS-VF) and mortality. METHODS: We conducted a cohort study comprising 11,120 participants. We employed weighted multivariable Cox regression analysis to assess the relationship between METS-VF and mortality. Restricted cubic spline analyses were used to investigate potential non-linear associations. Receiver operating characteristic curves were used to evaluate the predictive value of METS-VF and other obesity-related indicators for mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of the results. Mendelian randomization analysis was utilized to assess potential causality. RESULTS: Over a median follow-up duration of 83 months, a total of 1014 all-cause deaths, 301 cardiovascular deaths, and 262 cancer deaths occurred. For every 0.2-unit increase in METS-VF, the hazard ratios(HRs) of all-cause mortality, cardiovascular mortality, and cancer mortality were 1.13 [95% confidence interval (CI): 1.06, 1.20], 1.18 (95% CI: 1.06, 1.31), and 1.13 (95% CI: 1.03, 1.25), respectively. In addition, restricted cubic spline analyses revealed no significant non-linear associations between METS-VF and all-cause mortality, cardiovascular mortality, and cancer mortality. In multivariate Cox regression models, hazard ratios of all-cause mortality, cardiovascular mortality and cancer mortality were higher in the highest METS-VF group compared to the reference group. Subgroup and sensitivity analyses confirmed that our results were robust. Receiver operating characteristic curves indicated that METS-VF predicted mortality better than other obesity-related indicators. Mendelian randomization analysis confirmed significant causal relationships. CONCLUSIONS: METS-VF was positively associated with all-cause mortality, cardiovascular mortality, and cancer mortality. These findings suggest that METS-VF could serve as a straightforward, reliable, and cost-effective marker for identifying individuals at high risk of mortality.

Serum α-Klotho with all-cause and cause-specific mortality.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Novel Approach to Analyze Disparities in Colorectal Cancer Screening and Mortality.

INTRODUCTION: Reducing disparities in colorectal cancer (CRC) screening rates and mortality remains a priority. Mitigation strategies to reduce these disparities have largely been unsuccessful. The primary aim is to determine variables in models of healthcare utilization and their association with CRC screening and mortality in North Carolina. METHODS: A cross-sectional analysis of publicly available data across North Carolina using variable reduction techniques with clustering to evaluate association of CRC screening rates and mortality was performed. RESULTS: Three million sixty-five thousand five hundred thirty-seven residents (32.1%) were aged 50 y or more. More than two-thirds (68.8%) were White, while 20.5% were Black. Approximately 61% aged 50 y or more underwent CRC screening (range: 44.0%-80.5%) and had a CRC mortality of 44.8 per 100,000 (range 22.8 to 76.6 per 100,000). Cluster analysis identified two factors, designated social economic education index (factor 1) and rural provider index (factor 2) for inclusion in the multivariate analysis. CRC screening rates were associated with factor 1, consisting of socioeconomic and education variables, and factor 2, comprised of the number of providers per 10,000 individuals aged 50 y or more and rurality. An increase in both factors 1 and 2 by one point would result in an increase in CRC screening rated by 6.8%. CRC mortality was associated with factor 2. An increase in one point in factor 1 results in a decrease in mortality risk by 10.9%. CONCLUSIONS: In North Carolina, using variable reduction with clustering, CRC screening rates were associated with the inter-relationship of the number of providers and rurality, while CRC mortality was associated with the inter-relationship of social, economic, and education variables.

Overall glycaemic index and dietary glycaemic load and all-cause and cause-specific mortality in women from the Mexican Teachers' Cohort.

Previous studies have found direct associations between glycaemic index (GI) and glycaemic load (GL) with chronic diseases. However, this evidence has not been consistent in relation to mortality, and most data regarding this association come from high-income and low-carbohydrate-intake populations. The aim of this study was to evaluate the association between the overall GI and dietary GL and all-cause mortality, CVD and breast cancer mortality in Mexico. Participants from the Mexican Teachers' Cohort (MTC) study in 2006-2008 were followed for a median of 10 years. Overall GI and dietary GL were calculated from a validated FFQ. Deaths were identified by the cross-linkage of MTC participants with two national mortality registries. Cox proportional hazard models were used to estimate the impact of GI and GL on mortality. We identified 1198 deaths. Comparing the lowest and highest quintile, dietary GI and GL appeared to be marginally associated with all-cause mortality; GI, 1·12 (95 % CI: 0·93, 1·35); GL, 1·12 (95 % CI: 0·87, 1·44). Higher GI and GL were associated with increased risk of CVD mortality, GI, 1·30 (95 % CI: 0·82, 2·08); GL, 1·64 (95 % CI: 0·87, 3·07) and with greater risk of breast cancer mortality; GI, 2·13 (95 % CI: 1·12, 4·06); GL, 2·43 (95 % CI: 0·90, 6·59). It is necessary to continue the improvement of carbohydrate quality indicators to better guide consumer choices and to lead the Mexican population to limit excessive intake of low-quality carbohydrate foods.