Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Clinical Significance of Background Parenchymal Enhancement in Breast Cancer Risk Stratification.

BACKGROUND: Background parenchymal enhancement (BPE) is an established breast cancer risk factor. However, the relationship between BPE levels and breast cancer risk stratification remains unclear. PURPOSE: To evaluate the clinical relationship between BPE levels and breast cancer risk with covariate adjustments for age, ethnicity, and hormonal status. STUDY TYPE: Retrospective. POPULATION: 954 screening breast MRI datasets representing 721 women divided into four cohorts: women with pathogenic germline breast cancer (BRCA) mutations (Group 1, N = 211), women with non-BRCA germline mutations (Group 2, N = 60), women without high-risk germline mutations but with a lifetime breast cancer risk of ≥20% using the Tyrer-Cuzick model (Group 3, N = 362), and women with <20% lifetime risk (Group 4, N = 88). FIELD STRENGTH/SEQUENCE: 3 T/axial non-fat-saturated T1, short tau inversion recovery, fat-saturated pre-contrast, and post-contrast T1-weighted images. ASSESSMENT: Data on age, body mass index, ethnicity, menopausal status, genetic predisposition, and hormonal therapy use were collected. BPE levels were evaluated by two breast fellowship-trained radiologists independently in accordance with BI-RADS, with a third breast fellowship-trained radiologist resolving any discordance. STATISTICAL TESTS: Propensity score matching (PSM) was utilized to adjust covariates, including age, ethnicity, menopausal status, hormonal treatments, and prior bilateral oophorectomy. The Mann-Whitney U test, chi-squared test, and univariate and multiple logistic regression analysis were performed, with an odds ratio (OR) and corresponding 95% confidence interval. Weighted Kappa statistic was used to assess inter-reader variation. A P value <0.05 indicated a significant result. RESULTS: In the assessment of BPE, there was substantial agreement between the two interpreting radiologists (κ = 0.74). Patient demographics were not significantly different between patient groups after PSM. The BPE of Group 1 was significantly lower than that of Group 4 and Group 3 among premenopausal women. In estimating the BPE level, the OR of gene mutations was 0.35. DATA CONCLUSION: Adjusting for potential confounders, the BPE level of premenopausal women with BRCA mutations was significantly lower than that of non-high-risk women. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Quantitative assessment of background parenchymal enhancement is associated with lifetime breast cancer risk in screening MRI.

OBJECTIVES: To compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI. MATERIALS AND METHODS: This study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann-Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values. RESULTS: Age, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PEFGT (11.5 vs. 8.0%, adjusted p = 0.018) and SERFGT (7.2 vs. 9.3%, adjusted p = 0.066). CONCLUSION: Quantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE. CLINICAL RELEVANCE STATEMENT: BRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models. KEY POINTS: Expanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols. Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers. This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations.

The lifetime risk of surgery in England: a nationwide observational cohort study.

BACKGROUND: The average number of times a person will have surgery in their lifetime, and the amount of surgical healthcare resources they use, is unknown. Lifetime risk is a measure of the risk of an average person having a specific event within their lifetime. We report the lifetime risk of surgery and the change observed during the first year of the COVID-19 pandemic. METHODS: We conducted a population cohort study using hospital episode statistics to identify all patients undergoing surgery between January 1, 2016, and December 31, 2020, in England. We calculated age- and sex-specific incidence rates of surgery and combined these with routinely available population and mortality data from the Office for National Statistics. We computed the probability of requiring surgery stratified by 5-yr epochs (age 0-4 to ≥90 yr). Our primary analysis calculated lifetime risk for all surgery using the life table method. We assessed the impact of the COVID-19 pandemic, comparing a pre-pandemic and a pandemic period. RESULTS: Between 2016 and 2020, 23 427 531 patients underwent surgery, of which 11 937 062 were first surgeries. The average denominator population for England was 55.9 million. The lifetime risk of first surgery was 60.2% (95% confidence interval 55.1-65.4%) for women and 59.1% (95% confidence interval 54.2-64.1%) for men. The COVID-19 pandemic decreased the lifetime risk of first surgery by 32.3% for women and by 31.7% for men. This estimated lifetime risk should only be applied to the English population. CONCLUSIONS: This population epidemiological analysis suggests that approximately 60% of people in England will undergo surgery in their lifetime.

Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

[Translated article] Basal Cell Carcinoma: Incidence and Trends in Valencia, Spain.

BACKGROUND: There is a need for epidemiological and incidence data on the occurrence of basal cell carcinoma (BCC) in Spain. OBJECTIVES: Our study was designed to retrospectively retrieve cases from our computer databases from 2010 through 2016 to provide updated data on the actual incidence of BCC in Valencia, eastern Spain. MATERIAL AND METHODS: This was an epidemiological study on basal cell carcinoma conducted in Valencia, eastern Spain. We analyzed a total of 2171 patients and 4047 tumors, and gathered data to estimate the actual incidence of BBC in our region. RESULTS AND CONCLUSIONS: Our study confirmed that the incidence of BCC is much higher than previously reported. We calculated a crude incidence of 410.38 BCCs/100 000 person-years, an adjusted rate for the European population of 256.98 BCCs/100 000 person-years, and an adjusted rate for the world population of 196.26 BCCs/100 000 person-years. Risk is up to 29.49% higher for men (464.07 cases/100 000 person-years vs 358.40 cases/100 000 person-years for women). Incidence also increases by an annual 3.91% (a significantly higher annual incidence of 8.28% in women vs a 0.92% annual incidence in men). Overall, the lifetime risk for developing a BCC is 5.8% (5.02% in women and 7% in men).

Basal Cell Carcinoma: Incidence and Trends in Valencia, Spain. / Carcinoma basocelular: incidencia y tendencias en Valencia (España).

BACKGROUND: There is a need for epidemiological and incidence data on the occurrence of basal cell carcinoma (BCC) in Spain. OBJECTIVES: Our study was designed to retrospectively retrieve cases from our computer databases from 2010 through 2016 to provide updated data on the actual incidence of BCC in Valencia, eastern Spain. MATERIAL AND METHODS: This was an epidemiological study on basal cell carcinoma conducted in Valencia, eastern Spain. We analyzed a total of 2171 patients and 4047 tumors, and gathered data to estimate the actual incidence of BBC in our region. RESULTS AND CONCLUSIONS: Our study confirmed that the incidence of BCC is much higher than previously reported. We calculated a crude incidence of 410.38 BCCs/100 000 person-years, an adjusted rate for the European population of 256.98 BCCs/100 000 person-years, and an adjusted rate for the world population of 196.26 BCCs/100 000 person-years. Risk is up to 29.49% higher for men (464.07 cases/100 000 person-years vs 358.40 cases/100 000 person-years for women). Incidence also increases by an annual 3.91% (a significantly higher annual incidence of 8.28% in women vs a 0.92% annual incidence in men). Overall, the lifetime risk for developing a BCC is 5.8% (5.02% in women and 7% in men).

Effect of body mass index trajectory on lifetime risk of cardiovascular disease in a Chinese population: A cohort study.

BACKGROUND AND AIMS: The longitudinal trajectories of body mass index (BMI) can reflect the pattern of BMI changes. Lifetime risk quantifies the cumulative risk of developing a disease over the remaining life of a person. We aimed to identify the trajectory of BMI and explore its association with cardiovascular disease (CVD) in the Chinese population. METHODS AND RESULTS: A total of 68,603 participants with a mean age of 55.46 years were included from the Kailuan cohort in Tangshan, China, who were free of CVD and cancer and with repeated measurements of BMI from 2006 to 2010. A latent mixture model was used to identify BMI trajectories. An improved Kaplan-Meier estimator was used to predict the lifetime risk of CVD according to BMI trajectories. During a median follow-up of 7.0 years, 3325 participants developed CVD. Five BMI trajectories were identified at three index ages (35, 45, and 55) respectively. For index age 35 years, compared with the stable low-normal weight group (22.7% [95% CI, 20.0%-25.4%]), the stable high-normal weight (27.6% [25.6%-29.5%]), stable overweight (29.4% [27.4%-31.4%]), stable-low obesity (32.8% [30.0%-35.5%]), and stable-high obesity (38.9% [33.3%-44.5%]) groups had a higher lifetime risk of CVD (P < 0.05). We observed similar patterns for stroke and myocardial infarction. Similarly, the lifetime risk of CVD was higher in the long-term overweight and obese groups at 45 and 55 index ages. CONCLUSIONS: Long-term overweight and obesity were associated with an increased lifetime risk of CVD. Our findings could assist in predicting the population burden of CVD.

The lifetime risk of developing type II diabetes in an urban community in Mumbai: findings from a ten-year retrospective cohort study.

BACKGROUND: Incidence and prevalence do not capture the risk of developing diabetes during a defined period and only limited evidence exists on the lifetime risk of diabetes based on longer and continuous follow-up studies in India. Lacunae in evidence on lifetime risk can be attributed primarily to the absence of comprehensive and reliable information on diabetes incidence, mortality rates and lack of longitudinal studies in India. In light of the scarcity of evidence in India, the objective of this study was to estimate the incidence of diabetes and its lifetime risk in an urban community of Mumbai. METHODS: The research study utilized data which is extracted from the electronic medical records of beneficiaries covered under the Contributory Health Service Scheme in Mumbai. The dataset included information on 1652 beneficiaries aged 40 years and above who were non-diabetic in 2011-2012, capturing their visit dates to medical center and corresponding laboratory test results over a span ten years from January, 2012- December, 2021. Survival analysis techniques are applied to estimate the incidence of diabetes. Subsequently, the remaining life years from the life table were utilized to estimate the lifetime risk of diabetes for each gender, stratified by age group. RESULTS: A total of 546 beneficiaries developed diabetes in ten years, yielding an unadjusted incidence rate of 5.3 cases per 1000 person-years (95% CI: 4.9- 5.8 cases/ 1000 person years). The age-adjusted lifetime risk of developing type II diabetes in this urban community is estimated to be 40.3%. Notably, males aged 40 years and above had 41.5% chances of developing diabetes in their lifetime as compared to females with a risk of 39.4%. Moreover, the remaining lifetime risk of diabetes decreased with advancing age, ranging from 26.4% among 40-44 years old to 4.2% among those age 70 years and above. CONCLUSION: The findings stress the significance of recognizing age specific lifetime risk and implementing early interventions to prevent or delay diabetes onset and to focus on diabetes management programs in India.

Radiation dose and lifetime risk for radiation-induced cancer due to natural radioactivity in tap water from Jordan.

The purpose of this study was to investigate the radiological quality of drinking water in Ma'an governorate, which includes the archeological city of Petra and is one of Jordan's most important tourist destinations. To the best of the authors' knowledge, this is the first study in southern Jordan that investigates radioactivity in drinking water and its potential to cause cancer. A liquid scintillation detector was used to measure gross alpha and gross beta activities in tap water samples from Ma'an governorate. A high-purity Germanium detector was used to measure the activity concentrations of 226Ra and 228Ra. Gross alpha, gross beta, 226Ra, and 228Ra activities were < 110-724 mBq/l, < 220-362 mBq/l, < 11-241 mBq/l, and < 32-49 mBq/l, respectively. The results were compared to internationally recommended levels and literature values. Annual effective doses ([Formula: see text]) from 226 and 228Ra intake were calculated for infants, children, and adults. The highest doses were found for children while the lowest were found for infants. For each water sample, the lifetime risk of radiation-induced cancer (LTR) was calculated for the whole population. All of the LTR values were lower than the value recommended by the World Heath Organisation. It is concluded that there are no significant radiation-related health risks associated with consumption of tap water from the studied region.

Effects of communicating lifetime risks and screening rates of colorectal cancer and breast cancer.

Colorectal cancer and breast cancer are among the most common types of cancer in the United States, and cancer screening is an effective way to detect and treat these cancers early. Health news stories, medical websites, and media campaigns regularly highlight the national lifetime risks of specific cancers and their screening rates, but recent research suggests that people tend to overestimate the prevalence of health problems but underestimate the prevalence of disease prevention behaviors in the absence of numerical information. This study featured two online experiments, one focused on breast cancer (N = 632) and one focused on colorectal cancer (N = 671), to examine the effects of communicating national cancer lifetime risks and screening rates among samples of screening-eligible adults in the United States. Findings confirmed prior work in showing that people overestimated colorectal/breast cancer lifetime risks but underestimated colorectal/breast cancer screening rates. Communicating the national lifetime risk of dying from colorectal/breast cancer lowered people's national risk estimates, which in turn was associated with lower perceived cancer risks for themselves. In contrast, communicating the national colorectal/breast cancer screening rate increased people's estimates of the prevalence of cancer screening, which in turn was associated with higher perceived self-efficacy to engage in cancer screening and greater screening intentions. We conclude that efforts to promote cancer screening may benefit from messages that include data on national cancer screening rates but may not benefit from including national rates of lifetime cancer risks.

Radioactivity amounts, annual effective dose rate, and lifetime cancer risk estimation of some vegetable and fruit samples cultivated in Kahramanmaras, Turkey.

In this research, examples of the fruits and vegetables cultivated in Kahramanmaras, 238U, 232Th, and 40K levels, were detected, and in the case of consumption of these vegetables and fruits, for several age categories (adults, children (10 years old), and infants), annually effective dose rates and lifetime cancer risks were calculated. In fruit samples, concentrations of 238U, 232Th, and 40K ranged from under detection limit (UDL) to 15.29 ± 1.14 Bq/kg, 0.30 ± 0.01 to 13.23 ± 1.60 Bq/kg, and 5.82 ± 0.21 to 179.82 ± 1.34 Bq/kg, respectively. The mean concentrations of 238U, 232Th, and 40K in fruit samples were 5.31 ± 0.44 Bq/kg, 2.72 ± 0.26 Bq/kg, and 56.84 ± 0.57 Bq/kg, respectively. In vegetable samples, concentrations of 238U, 232Th, and 40K ranged from 0.48 ± 0.04 to 11.77 ± 0.95 Bq/kg, 0.55 ± 0.04 to 4.57 ± 0.44 Bq/kg, and 9.32 ± 0.43 to 52.44 ± 0.52 Bq/kg, respectively. The mean concentrations of 238U, 232Th, and 40K in the vegetable samples were 6.58 ± 0.65 Bq/kg, 2.72 ± 0.27 Bq/kg, and 27.09 ± 0.27 Bq/kg, respectively. The mean annual effective dose rates for adults, children (10 years old), and infants in fruit samples were 0.184 ± 0.001 mSv/y, 0.288 ± 0.002 mSv/y, and 0.304 ± 0.003 mSv/y, respectively. The average lifetime cancer risks for adults, children (10 years old), and infants in fruit samples were 0.647 ± 0.006 × 10-4, 1.011 ± 0.010 × 10-4, and 1.067 ± 0.010 × 10-4, respectively. The mean annual effective dose rates for adults, children (10 years old), and infants in the vegetable samples were 0.118 ± 0.001 mSv/y, 0.128 ± 0.001 mSv/y, and 0.086 ± 0.001 mSv/y, respectively. The mean lifetime cancer risks for adults, children (10 years old), and infants in vegetable samples were 0.416 ± 0.004 × 10-4, 0.449 ± 0.004 × 10-4, and 0.304 ± 0.003 × 10-4, respectively.

A comparison of statistical methods to predict the residual lifetime risk.

Lifetime risk measures the cumulative risk for developing a disease over one's lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.

Lifetime risk of cardiovascular disease and life expectancy with and without cardiovascular disease according to changes in metabolic syndrome status.

BACKGROUND AND AIMS: The relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status. METHODS AND RESULTS: Dynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan-Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%-41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%-42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%-45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%-30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years). CONCLUSIONS: Recovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.

Lifetime risk of diabetes in metropolitan cities in India.

AIMS/HYPOTHESIS: We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI. METHODS: A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by the Government of India (2014); and prevalence of diabetes from the Indian Council for Medical Research INdia DIABetes study (2008-2015). RESULTS: Lifetime risk (95% CI) of diabetes in 20-year-old men and women was 55.5 (51.6, 59.7)% and 64.6 (60.0, 69.5)%, respectively. Women generally had a higher lifetime risk across the lifespan. Remaining lifetime risk (95% CI) declined with age to 37.7 (30.1, 46.7)% at age 60 years among women and 27.5 (23.1, 32.4)% in men. Lifetime risk (95% CI) was highest among obese Indians: 86.0 (76.6, 91.5)% among 20-year-old women and 86.9 (75.4, 93.8)% among men. We identified considerably higher diabetes-free life expectancy at lower levels of BMI. CONCLUSIONS/INTERPRETATION: Lifetime risk of diabetes in metropolitan cities in India is alarming across the spectrum of weight and rises dramatically with higher BMI. Prevention of diabetes among metropolitan Indians of all ages is an urgent national priority, particularly given the rapid increase in urban obesogenic environments across the country. Graphical abstract.

Cancer incidence and cancer death in relation to tobacco smoking in a population-based Australian cohort study.

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.

Estimating the direct effect of human papillomavirus vaccination on the lifetime risk of screen-detected cervical precancer.

Birth cohorts vaccinated against human papillomavirus (HPV) are now entering cervical cancer screening. Assessment of (pre)cancer (CIN3+) risk is needed to assess the residual screening need in vaccinated women. We estimated the lifetime (screen-detected) CIN3+ risk under five-yearly primary HPV screening between age 30 and 60, using HPV genotyping and histology data of 21,287 women participating in a screening trial with two HPV-based screening rounds, 5 years apart. The maximum follow-up after an HPV-positive test was 9 years. We re-estimated the CIN3+ risk after projecting direct vaccine efficacy for the bivalent and the nonavalent HPV vaccines, assuming life-long protection. The lifetime CIN3+ risk was 4.1% (95% confidence interval 3.5-4.9) and declined by 53.5% and 70.5% after bivalent vaccination without and with cross-protection, respectively, translating into a residual lifetime CIN3+ risk of 1.9% (1.4-2.4) and 1.2% (0.9-1.5). The CIN3+ risk declined by 88.5% after nonavalent vaccination, translating into a residual lifetime CIN3+ risk of 0.5% (0.2-0.7). The latter risk increased to 1.6% when vaccine protection only lasted until the first screening round at age 30. Among HPV-positive women with abnormal adjunct cytology, the nine-year CIN3+ risk was 16.9% (8.7-32.4) after nonavalent vaccination. In conclusion, HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk and the remaining absolute CIN3+ risk will be very low. Primary HPV testing combined with adjunct cytology at five-year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost-effective. Our results support a de-intensification of screening programs in settings with high vaccination coverage.

Development and Validation of a Large Synthetic Cohort for the Study of Cardiovascular Health Across the Life Span.

We developed and validated a synthetic cohort approach to examine numbers of cardiovascular risk factors (CRFs) and adverse clinical events, including incident cardiovascular disease and all-cause mortality, across the life span from ages 20 years to 90 years. The current analysis included 40,875 participants from 7 large, population-based longitudinal epidemiologic studies (1948-2016). On the basis of a joint multilevel imputation model, we multiply imputed each participant's life-span numbers of CRFs and events using available records. To validate the imputed values, we partially removed the observed data and then compared the imputed and observed values. The complete life-span synthetic data set reflected the original observed data trends well. In our validation sample, the distributions of imputed CRFs and events were close to the observed distributions but with less variability. Bland-Altman plots indicated that there was a slightly negative trend in general, and the agreement bias was relatively small for the continuous CRFs. The hypothetical linear regression model suggested that the relationships between the CRFs and events were preserved in the imputed data set. This approach generated valid estimates of CRFs and events across the life span for African-American and White participants. The synthetic cohort may be sufficiently accurate to be useful in assessing the origins and timing of accumulating cardiovascular risk that can inform efforts to avoid cardiovascular disease development.

Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project.

BACKGROUND: Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG). METHODS: Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan-Meier analysis, Cox models adjusted for the competing risk of death, and Irwin's restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40-59 years) and older (60-79 years) adults with FPG < 100 mg/dL, prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) across race-sex groups. RESULTS: In 40,117 participants with 638,910 person-years of follow-up, 4846 cases of incident HF occurred. The lifetime risk of HF was significantly higher among middle-aged White adults and Black women with prediabetes (range: 6.1% [95% CI 4.8%, 7.4%] to 10.8% [95% CI 8.3%, 13.4%]) compared with normoglycemic adults (range: 3.5% [95% CI 3.0%, 4.1%] to 6.5% [95% CI 4.9%, 8.1%]). Middle-aged Black women with diabetes had the highest lifetime risk (32.4% [95% CI 26.0%, 38.7%]) and aHR (4.0 [95% CI 3.0, 5.4]) for HF across race-sex groups. Middle-aged adults with prediabetes and diabetes lived on average 0.9-1.6 and 4.1-6.0 fewer years free from HF, respectively. Findings were similar in older adults except older Black women with prediabetes did not have a higher lifetime risk of HF. CONCLUSIONS: Prediabetes was associated with higher lifetime risk of HF in middle-aged White adults and Black women, with the association attenuating in older Black women. Black women with diabetes had the highest lifetime risk of HF compared with other race-sex groups.

Visit-to-visit fasting blood glucose variability and lifetime risk of cardiovascular disease: a prospective study.

AIMS: Previous studies suggested an adverse association between higher fasting blood glucose (FBG) variability and cardiovascular disease (CVD). Lifetime risk provides an absolute risk assessment during the remainder of an individual's life. However, the association between FBG variability and the lifetime risk of CVD is uncertain. OBJECTIVE: We aimed to investigate the effect of the visit-to-visit FBG variability on the lifetime risk of CVD. METHODS: This study included participants from the Kailuan Study who did not have CVD at index ages 35, 45, and 55 years. The FBG variability was defined as the coefficient of variation (CV) of three FBG values that were measured during the examination periods of 2006-2007, 2008-2009, and 2010-2011. We used a modified Kaplan-Merrier method to estimate lifetime risk of CVD according to tertiles of FBG variability. RESULTS: At index age 35 years, the study sample comprised 46,018 participants. During a median follow-up of 7.0 years, 1889 participants developed CVD events. For index age 35 years, participants with high FBG variability had higher lifetime risk of CVD (32.5%; 95% confidence interval [CI]: 28.9-36.1%), compared with intermediate (28.3%; 95% CI: 25.5 -31.1%) and low (26.3%; 95% CI: 23.0-29.5%) FBG variability. We found that higher FBG variability was associated with increased lifetime risk of CVD in men but not women. Similar patterns were observed at index ages 45 and 55 years. CONCLUSIONS: Higher FBG variability was associated with increased lifetime risk of CVD at each index age. Focusing on the FBG variability may provide an insight to the clinical utility for reducing the lifetime risk of CVD.