The future burden of oesophageal and stomach cancers attributable to modifiable behaviours in Australia: a pooled cohort study.

BACKGROUND: We quantified the individual and joint contribution of contemporaneous causal behavioural exposures on the future burden of oesophageal and stomach cancers and their subtypes and assessed whether these burdens differ between population groups in Australia, as such estimates are currently lacking. METHODS: We combined hazard ratios from seven pooled Australian cohorts (N = 367,058) linked to national cancer and death registries with exposure prevalence from the 2017-2018 National Health Survey to estimate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death. RESULTS: Current and past smoking explain 35.2% (95% CI = 11.7-52.4%), current alcohol consumption exceeding three drinks/day 15.7% (95% CI = 0.9-28.4%), and these exposures jointly 41.4% (95% CI = 19.8-57.3%) of oesophageal squamous cell carcinomas in Australia. Current and past smoking contribute 38.2% (95% CI = 9.4-57.9%), obesity 27.0% (95% CI = 0.6-46.4%), and these exposures jointly 54.4% (95% CI = 25.3-72.1%) of oesophageal adenocarcinomas. Overweight and obesity explain 36.1% (95% CI = 9.1-55.1%), current and past smoking 24.2% (95% CI = 4.2-40.0%), and these exposures jointly 51.2% (95% CI = 26.3-67.8%) of stomach cardia cancers. Several population groups had a significantly higher smoking-attributable oesophageal cancer burden, including men and those consuming excessive alcohol. CONCLUSIONS: Smoking is the leading preventable behavioural cause of oesophageal cancers and overweight/obesity of stomach cancers.

Changes in Dietary Total and Nonheme Iron Intake Is Associated With Incident Frailty in Older Men: The Concord Health and Aging in Men Project.

BACKGROUND: Nutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty. METHODS: Cross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression. RESULTS: Incidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile -2.61-0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]). CONCLUSION: Maintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men.

Dementia Incidence, APOE Genotype, and Risk Factors for Cognitive Decline in Aboriginal Australians: A Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: Aboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown. METHODS: A population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age. APOE genotyping was available for 86 people. RESULTS: Data were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34-53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42-3.70), male sex (OR 4.14, 95% CI 1.60-10.77), unskilled work history (OR 5.09, 95% CI 1.95-13.26), polypharmacy (OR 3.11, 95% CI 1.17-8.28), and past smoking (OR 0.24, 95% CI 0.08-0.75) were associated with incident MCI/dementia in the final model. APOE ε4 allele frequency was 24%; heterozygous or homozygous ε4 was associated with incident MCI/dementia (bivariate OR 3.96, 95% CI 1.25-12.50). DISCUSSION: These findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.

Thyroid cancers potentially preventable by reducing overweight and obesity in Australia: A pooled cohort study.

Thyroid cancer incidence and the prevalence of overweight and obesity are increasing, but the future thyroid cancer burden attributable to contemporary levels of overweight and obesity has not been evaluated before. We quantified this burden in Australia, and assessed whether the overweight/obesity-attributable burden differed by sex or other population subgroupings. We estimated the strength of the associations of overweight and obesity with thyroid cancer with adjusted proportional hazards models using pooled data from seven Australian cohorts (N = 367 058) with 431 thyroid cancer cases ascertained from linked national cancer registry data during a maximum 22-year follow-up. We combined these estimates with nationally representative 2017 to 2018 estimates of overweight and obesity prevalence to estimate population attributable fractions (PAFs) of future thyroid cancers attributable to overweight and obesity, accounting for competing risk of death, and compared PAFs for population subgroups. Contemporary levels of overweight and obesity explain 18.6% (95% confidence interval [CI] = 5.2%-30.2%), and obesity alone 13.7% (95% CI: 5.2%-21.4%), of the future thyroid cancer burden. The obesity-attributable thyroid cancer burden is 21.4% (95% CI: 2.8%-36.5%) for men and 10.1% (95% CI: 0.8%-18.6%) for women. Were the currently obese overweight instead, 9.9% (95% CI: 1.0%-18.1%) of thyroid cancers could be avoided. The relative overweight/obesity-attributable burden is higher for those consuming on average more than two alcoholic drinks per day (63.4%) and for those who are not married/co-habiting (33.2%). In conclusion, avoiding excess weight, especially obesity, should be a priority for thyroid cancer prevention. Further studies, with findings stratified by tumour size, may reveal the potential role of overdiagnosis in our results.

The Future Burden of Head and Neck Cancers Attributable to Modifiable Behaviors in Australia: A Pooled Cohort Study.

BACKGROUND: Estimates of future burden of cancer attributable to current modifiable causal exposures can guide cancer prevention. We quantified future head and neck cancer burden in Australia attributable to individual and joint causal exposures, and assessed whether these burdens differ between population subgroups. METHODS: We estimated the strength of the associations between exposures and head and neck cancer using adjusted proportional hazards models from pooled data from seven Australian cohorts (N = 367,058) linked to national cancer and death registries and estimated exposure prevalence from the 2017 to 2018 Australian National Health Survey. We calculated population attributable fractions (PAF) with 95% confidence intervals (CI), accounting for competing risk of death, and compared PAFs for population subgroups. RESULTS: Contemporary levels of current and former smoking contribute 30.6% (95% CI, 22.7%-37.8%), alcohol consumption exceeding two standard drinks per day 12.9% (95% CI, 7.6%-17.9%), and these exposures jointly 38.5% (95% CI, 31.1%-45.0%) to the future head and neck cancer burden. Alcohol-attributable burden is triple and smoking-attributable burden is double for men compared with women. Smoking-attributable burden is also at least double for those consuming more than two alcoholic drinks daily or doing less than 150 minutes of moderate or 75 minutes of vigorous activity weekly, and for those aged under 65 years, unmarried, with low or intermediate educational attainment or lower socioeconomic status, compared with their counterparts. CONCLUSIONS: Two-fifths of head and neck cancers in Australia are preventable by investment in tobacco and alcohol control. IMPACT: Targeting men and other identified high-burden subgroups can help to reduce head and neck cancer burden disparities.

Dietary and supplemental antioxidant intake and risk of major adverse cardiovascular events in older men: The concord health and ageing in men project.

BACKGROUND AND AIMS: The role of antioxidant intake in cardiovascular disease remains inconclusive. This study evaluates the association between antioxidant intake and the risk of major adverse cardiovascular events (MACE) among older Australian men. METHODS AND RESULTS: 794 men aged ≥75 years participated in the 3rd wave of the Concord Health and Ageing in Men Project. Dietary adequacy of antioxidant intake was assessed by comparing participants' intake of vitamins A, E, C and zinc to the Nutrient Reference Values (NRV) for Australia. Attainment of NRVs of antioxidants was categorised into a dichotomised variable 'inadequate' (meeting≤2 of 4 antioxidants) or 'adequate' (meeting≥3 of 4 antioxidants). The usage of antioxidant supplements was assessed. The outcome measure was MACE. The composite MACE endpoint was defined as having one of the following: death, myocardial infarction, ischemic stroke, congestive cardiac failure (CCF), and revascularization during the period of observation. There was no significant association between dietary (HR: 1.03, 95% CI: 0.71, 1.48) or supplemental antioxidant intake (HR: 1.10, 95% CI: 0.75, 1.63) and overall MACE. However, a significant association was observed between inadequate antioxidant intake and CCF (HR: 1.32; 95% CI: 1.16, 1.50). The lowest quartile of zinc intake (<11.00 mg/d) was significantly associated with CCF (HR 2.36; 95% CI: 1.04, 5.34). None of the other antioxidants were significantly associated with CCF or other MACE components. CONCLUSION: Inadequate dietary antioxidant intake, particularly zinc, is associated with increased risk of CCF in older Australian men but not associated with overall MACE.

The association between antioxidant intake, dietary pattern and depressive symptoms in older Australian men: the Concord Health and Ageing in Men Project.

PURPOSE: The objectives of the study were to evaluate the associations between antioxidant intake, dietary patterns and depressive symptoms among older men. METHOD: 794 men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project 3rd wave (considered baseline nutrition) and 781 men participated at the 4th wave (considered 3-year follow-up). Depressive symptoms were measured using the Geriatric Depression Scale (GDS ≥ 5). Dietary adequacy of antioxidant intake was assessed by comparing participants' median intake of vitamin A, E, C and zinc to the Nutrient Reference Values for Australia. Attainment of NRVs of antioxidant was categorised into a dichotomised variable 'poor' (meeting ≤ 2) or 'good' (meeting ≥ 3). Individual antioxidant nutrient was categorised into quartiles. The Australian and Mediterranean diet scores were assessed as predictor variables. RESULTS: The prevalence of GDS ≥ 5 was 12.8% at baseline nutrition and 13.2% of men developed GDS ≥ 5 at a 3-year follow-up. There was a significant cross-sectional association between poor antioxidant intake and GDS ≥ 5 in adjusted analyses [OR: 1.95 (95% CI 1.03, 3.70)]. Poor antioxidant intake at baseline nutrition remained prospectively associated with incident GDS ≥ 5 [OR: 2.46 (95% CI 1.24, 4.88)] in adjusted analyses. This association was also found for the lowest quartile of zinc [OR 2.72 (95% CI 1.37, 5.42)] and vitamin E intake [OR 2.18 (95% CI 1.05, 4.51)]. None of the other antioxidants and dietary patterns had a significant association with incident depressive symptoms. CONCLUSION: Inadequacy of antioxidant intake, particularly zinc and vitamin E, is associated with increased risk of clinically significant depressive symptoms in older men.

Contribution of psychosocial factors to socioeconomic inequalities in mortality among older Australian men: a population-based cohort study.

BACKGROUND: Among older people, the extent to which psychosocial factors explain socioeconomic inequalities in mortality is debated. We aimed to investigate the potential mediating effect of psychosocial factors on socioeconomic inequalities in mortality. METHODS: We used data from a prospective population-based cohort (the Concord Health and Ageing in Men Project; baseline recruitment in 2005-2007), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Socioeconomic status (SES; educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score) was assessed at baseline. Measures of structural and functional social support, as well as depressive and anxiety symptoms were assessed three times during follow-ups. Associations were quantified using Cox regression. Mediation was calculated using "change-in-estimate method". RESULTS: 1522 men (mean age at baseline: 77·4 ± 5·5 years) were included in the analyses with a mean (SD) follow-up time of 9·0 (3·6) years for all-cause and 8·0 (2·8) years for cause-specific mortality. At baseline, psychosocial measures displayed marked social patterning. Being unmarried, living alone, low social interactions, and elevated depressive symptoms were associated with higher risk of all-cause and cardiovascular disease (CVD) mortality. Psychosocial factors explained 35% of SES inequalities in all-cause mortality, 29% in CVD mortality, 12% in cancer mortality, and 39% in non-CVD, non-cancer mortality. CONCLUSION: Psychosocial factors may account for up to one-third of SES inequalities in deaths from all and specific causes (except cancer mortality). Our findings suggest that interventional studies targeting social relationships and/or psychological distress in older men aiming to reduce socioeconomic inequalities in mortality are warranted.

Socioeconomic status, health-related behaviours, and death among older people: the Concord health and aging in men project prospective cohort study.

BACKGROUND: Conflicting evidence exists regarding the association of socioeconomic status (SES) with mortality among older people and little is known about the mechanisms underlying this association. We investigated the association of SES with mortality among older Australian men. We also investigated potential mediating effects of health-related behaviours in SES-mortality associations. METHODS: We used data from a prospective population-based cohort (the Concord Health and Aging in Men Project), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score were assessed at baseline. Longitudinally assessed alcohol consumption, smoking, physical activity, and body mass index were investigated as potential mediators. Associations were quantified using Cox regression. RESULTS: We evaluated 1527 men (mean age: 77.4 ± 5.5 years). During a mean follow-up time of 9.0 years, 783 deaths occurred. For deaths from all causes, the adjusted hazard ratio (HR) for the lowest tertile of cumulative SES score versus the highest tertile was 1.44 (95% CI 1.21 to 1.70); the corresponding sub-HRs were 1.35 (0.96 to 1.89) for cardiovascular disease (CVD) mortality; 1.58 (1.15 to 2.18) for cancer mortality, and 1.86 (1.36 to 2.56) for non-CVD, non-cancer mortality. SES-mortality associations were attenuated by 11-25% after adjustment for mediating health-related behaviours. CONCLUSION: Low SES is associated with increased mortality in older Australian men and health-related behaviours accounted for less than one-fourth of these associations. Further research is needed to fully understand the mechanisms underlying SES inequalities in mortality among older people.

Mortality Paradox of Older Italian-Born Men in Australia: The Concord Health and Ageing in Men Project.

Italian migrants are one of the largest groups of older migrants in Australia. Past research has found lower mortality rates in Italian migrants but it is unclear if this persists into older age. Data came from 334 Italian-born and 849 Australian-born men aged 70 years and over participating in a longitudinal study of men's ageing. Male Italian migrants were more likely to smoke, be overweight, and have lower socio-economic status (SES). They also had higher morbidity from diabetes, chronic pain, dementia and depressive symptoms but lower morbidity from heart disease and cancer. There was no age-adjusted mortality difference. However, adjusting for SES, lifestyle and morbidity differences revealed a 25% lower mortality rate (adjusted HR = 0.75; 95% CI 0.57, 0.98) in Italian-born men. Compared to their Australian-born counterparts, older Italian-born men have a lower mortality than expected considering their lower SES, higher smoking and higher morbidity.

The future burden of kidney and bladder cancers preventable by behavior modification in Australia: A pooled cohort study.

Substantial changes in the prevalence of the principal kidney and bladder cancer risk factors, smoking (both cancers) and body fatness (kidney cancer), have occurred but the contemporary cancer burden attributable to these factors has not been evaluated. We quantified the kidney and bladder cancer burden attributable to individual and joint exposures and assessed whether these burdens differ between population subgroups. We linked pooled data from seven Australian cohorts (N = 367,058) to national cancer and death registries and estimated the strength of the associations between exposures and cancer using adjusted proportional hazards models. We estimated exposure prevalence from representative contemporaneous health surveys. We combined these estimates to calculate population attributable fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death, and compared PAFs for population subgroups. During the first 10-year follow-up, 550 kidney and 530 bladder cancers were diagnosed and over 21,000 people died from any cause. Current levels of overweight and obesity explain 28.8% (CI = 17.3-38.7%), current or past smoking 15.5% (CI = 6.0-24.1%) and these exposures jointly 39.6% (CI = 27.5-49.7%) of the kidney cancer burden. Current or past smoking explains 44.4% (CI = 35.4-52.1%) of the bladder cancer burden, with 24.4% attributable to current smoking. Ever smoking explains more than half (53.4%) of the bladder cancer burden in men, and the burden potentially preventable by quitting smoking is highest in men (30.4%), those aged <65 years (28.0%) and those consuming >2 standard alcoholic drinks/day (41.2%). In conclusion, large fractions of kidney and bladder cancers in Australia are preventable by behavior change.

Prospective Associations Between Dietary Antioxidant Intake and Frailty in Older Australian Men: The Concord Health and Ageing in Men Project.

BACKGROUND: The objective of the study is to evaluate the prospective associations between antioxidant intake and incident frailty among older Australian men aged ≥75 years. METHODS: Seven hundred and ninety-four men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project (CHAMP) study third wave (considered baseline nutrition here) and 781 men participated at the fourth wave (considered 3-year follow-up here). The main outcome measurement was incident frailty at 3-year follow-up, using the Cardiovascular Health Study definition. Dietary adequacy of antioxidant intake was assessed by comparing participants' median intakes of four dietary antioxidants (vitamin A, E, C, and zinc) to the nutrient reference values (NRVs). Attainment of the NRVs was incorporated into a dichotomized variable "poor" (meeting ≤2 antioxidants) or "good" (meeting ≥3 antioxidants) as the independent variable using the cut-point method. Also, intakes of each individual dietary antioxidant at baseline nutrition were categorized into quartiles. Analyses were performed using multinomial logistic regression. RESULTS: Incidence of pre-frailty was 53.0% and frailty was 6.4% at 3-year follow-up. Poor dietary antioxidant intake (meeting ≤2) at baseline nutrition was associated with incident frailty at 3-year follow-up in unadjusted (OR: 2.59 [95% CI: 1.47, 4.59, p = .001]) and adjusted (OR: 2.46 [95% CI: 1.10, 5.51, p = .03]) analyses. The lowest quartile of vitamin E intake (<7.08 mg/d) was significantly associated with incident frailty (OR: 2.46 [95% CI: 1.01, 6.00, p = .05]). CONCLUSIONS: Poor antioxidant intake, particularly vitamin E, is a plausible factor associated with incident frailty among older men. This supports the need for clinical trials of diets rich in antioxidants or possibly low-dose antioxidant supplements, for prevention of frailty.

Of Older Mice and Men: Branched-Chain Amino Acids and Body Composition.

Protein and branched-chain amino acid (BCAA) intake are associated with changes in circulating BCAAs and influence metabolic health in humans and rodents. However, the relationship between BCAAs and body composition in both species is unclear, with many studies questioning the translatability of preclinical findings to humans. Here, we assessed and directly compared the relationship between circulating BCAAs, body composition, and intake in older mice and men. Body weight and body fat were positively associated with circulating BCAA levels in both mouse and human, which remained significant after adjustments for age, physical activity, number of morbidities, smoking status, and source of income in the human cohort. Macronutrient intakes were similarly associated with circulating BCAA levels; however, the relationship between protein intake and BCAAs were more pronounced in the mice. These findings indicate that the relationship between circulating BCAAs, body composition, and intakes are comparable in both species, suggesting that the mouse is an effective model for examining the effects of BCAAs on body composition in older humans.

The preventable burden of endometrial and ovarian cancers in Australia: A pooled cohort study.

OBJECTIVE: Evidence on the endometrial and ovarian cancer burden preventable through modifications to current causal behavioural and hormonal exposures is limited. Whether the burden differs by population subgroup is unknown. METHODS: We linked pooled data from six Australian cohort studies to national cancer and death registries, and quantified exposure-cancer associations using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We then calculated Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death, and compared PAFs for population subgroups. RESULTS: During a median 4.9 years follow-up, 510 incident endometrial and 303 ovarian cancers were diagnosed. Overweight and obesity explained 41.9% (95% CI 32.3-50.1) of the endometrial cancer burden and obesity alone 34.5% (95% CI 27.5-40.9). This translates to 12,800 and 10,500 endometrial cancers in Australia in the next 10 years, respectively. The body fatness-related endometrial cancer burden was highest (49-87%) among women with diabetes, living remotely, of older age, lower socio-economic status or educational attainment and born in Australia. Never use of oral contraceptives (OCs) explained 8.1% (95% CI 1.8-14.1) or 2500 endometrial cancers. A higher BMI and current long-term MHT use increased, and long-term OC use decreased, the risk of ovarian cancer, but the burden attributable to overweight, obesity or exogenous hormonal factors was not statistically significant. CONCLUSIONS: Excess body fatness, a trait that is of high and increasing prevalence globally, is responsible for a large proportion of the endometrial cancer burden, indicating the need for effective strategies to reduce adiposity.

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study.

Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow-up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3-20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3-13.5%), and these factors combined 18.8% (CI = 9.1-27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2 ) explains 12.8% (CI = 7.8-17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8-8.9%), any regular alcohol consumption 6.6% (CI = 1.5-11.4%), and these factors combined 24.2% (CI = 17.6-30.3%). The MHT-related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio-economic status, the body fatness-related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol-related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population-level cancer control activities.

The burden of pancreatic cancer in Australia attributable to smoking.

OBJECTIVE: To estimate the burden of pancreatic cancer in Australia attributable to modifiable exposures, particularly smoking. DESIGN: Prospective pooled cohort study. SETTING, PARTICIPANTS: Seven prospective Australian study cohorts (total sample size, 365 084 adults); participant data linked to national registries to identify cases of pancreatic cancer and deaths. MAIN OUTCOME MEASURES: Associations between exposures and incidence of pancreatic cancer, estimated in a proportional hazards model, adjusted for age, sex, study, and other exposures; future burden of pancreatic cancer avoidable by changes in exposure estimated as population attributable fractions (PAFs) for whole population and for specific population subgroups with a method accounting for competing risk of death. RESULTS: There were 604 incident cases of pancreatic cancer during the first 10 years of follow-up. Current and recent smoking explained 21.7% (95% CI, 13.8-28.9%) and current smoking alone explained 15.3% (95% CI, 8.6-22.6%) of future pancreatic cancer burden. This proportion of the burden would be avoidable over 25 years were current smokers to quit and there were no new smokers. The burden attributable to current smoking is greater for men (23.9%; 95% CI, 13.3-33.3%) than for women (7.2%; 95% CI, -0.4% to 14.2%; P = 0.007) and for those under 65 (19.0%; 95% CI, 8.1-28.6%) than for older people (6.6%; 95% CI, 1.9-11.1%; P = 0.030). There were no independent relationships between body mass index or alcohol consumption and pancreatic cancer. CONCLUSIONS: Strategies that reduce the uptake of smoking and encourage current smokers to quit could substantially reduce the future incidence of pancreatic cancer in Australia, particularly among men.

Cross-Sectional and Longitudinal Relationships Between Inflammatory Biomarkers and Frailty in Community-dwelling Older Men: The Concord Health and Ageing in Men Project.

BACKGROUND: Previous studies demonstrated associations between IL-6 and frailty, but associations between a wide range of cytokines, chemokines, and growth factors with prevalent and incident frailty has not been studied. METHODS: Community-dwelling men aged more than 75 enrolled in the 5-year and 8-year follow-up of the CHAMP study were assessed. Twenty-seven inflammatory biomarkers were measured using the Bio-Plex Pro Human Cytokine 27-plex Assay kit at 5-year follow-up. Frailty was determined using the Fried frailty phenotype (FP) and Rockwood frailty index (FI) at both time-points. Age, body mass index, smoking, alcohol, and comorbidity were also assessed. RESULTS: In cross-sectional analysis of the 5-year follow-up, the unadjusted odds ratio (OR) for frail versus robust evaluated by the FP showed significant associations for IL-6 (OR: 1.56, 95% confidence interval [CI]: 1.23-1.98) and IL-8 (OR: 1.28, 95% CI: 1.00-1.63). IL-6 remained significantly associated in the age-adjusted (OR: 1.58, 95% CI: 1.21-2.05) and multivariable-adjusted model (OR: 1.54, 95% CI: 1.16-2.05). No associations were observed between pre-frail versus robust. In longitudinal unadjusted analysis, IL-8 (OR: 1.32, 95% CI: 1.03-1.70) and IP-10 (OR: 1.32, 95% CI: 1.03-1.70) at 5-year predicted incident frailty at 8-year follow-up. IL-8 remained longitudinally associated with incident frailty after age (OR: 1.34, 95% CI: 1.03-1.75) but not multivariable (OR: 1.20, 95% CI: 0.98-1.70) adjustment. Similar results were seen using the FI. None of the other biomarkers had significant associations with incident frailty. CONCLUSIONS: Our findings suggest that IL-6 and IL-8 may be cross-sectionally associated with frailty and that all measured inflammatory biomarkers were not causally related to frailty. Together with previous studies, the results suggest that frailty is specifically linked to IL-6 and IL-8 rather than simply representing a nonspecific pan-inflammatory condition.

Aldose Reductase Polymorphisms, Fasting Blood Glucose, and Age-Related Cortical Cataract.

Purpose: To determine whether there is an association between polymorphisms of the AKR1B1 gene and cortical cataract in the presence of hyperglycemia. Methods: In the second cross section of the Blue Mountains Eye Study (BMES), 3508 participants (2334 at 5-year follow-up and 1174 newly recruited participants) were examined during 1997 to 2000. Cataract was graded from lens photographs using the Wisconsin Cataract Grading System. Fasting blood glucose (FBG) was measured. Continuous imputed dosages of minor alleles of 17 AKR1B1 single nucleotide polymorphisms (SNPs) were assessed for associations with prevalent cortical cataract. Gene-environment interactions between SNPs and FBG were examined. Odds ratios (OR) and 95% confidence intervals (CI) for prevalent cortical cataract were estimated using logistic regression adjusting for age, sex, smoking, hypertension, education, and myopia. A P value of 0.005 was considered statistically significant after correction for 10 independent tests. Replication of significant associations found in the BMES sample was conducted in the Singapore Epidemiology of Eye Diseases (SEED) study (n = 10,033). Results: No polymorphism was associated with prevalent cortical cataract. A significant interaction was observed between rs9640883 and FBG (Pinteraction = 0.004), with increased cortical cataract prevalence associated with rs9640883 minor allele dosage in those with FBG >6.0 mM (strata-specific OR 1.72, 95% CI 1.09-2.72). No similar association was found in participants with normal FBG (OR 0.85, 95% CI 0.69-1.04). This interaction was not evident in the SEED study. Conclusions: The identified interaction between rs9640883 and FBG in relation to cortical cataract was not replicated but may warrant further investigation.

Six-Year Incidence of and Risk Factors for Cataract Surgery in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To report the 6-year incidence of cataract surgery in an Asian population-based cohort of Malay, Indian, and Chinese persons living in Singapore and factors associated with undergoing cataract surgery over the follow-up period. DESIGN: Population-based prospective cohort study. PARTICIPANTS: From 2004 through 2011, 10 033 participants (3280 Malays, 3400 Indians, and 3353 Chinese) 40 years of age or older participated in the Singapore Epidemiology of Eye Diseases Study. Six years later, 6762 participants (78.7% of those eligible, including 1901 Malays [72.1% of eligible], 2200 Indians [75.5% of eligible], and 2661 Chinese [87.7% of eligible]) were re-examined. METHODS: Detailed eye examinations including slit-lamp biomicroscopy were conducted at both visits. Logistic regression models were used to assess factors associated with cataract surgery after adjusting for age, gender, socioeconomic status, and other risk factors. MAIN OUTCOME MEASURE: Incident cataract surgery. RESULTS: The age-adjusted 6-year incidence of cataract surgery was 11.0% (9.5%, 12.6%, and 11.1% for Malays, Indians, and Chinese, respectively) and was strongly age related (P < 0.001 for trend). After adjustment, baseline factors associated with incident cataract surgery included older age (odds ratio [OR], 1.13 per 1-year increase; 95% confidence interval [CI], 1.11-1.14), diabetes (OR, 1.90; 95% CI, 1.54-2.33), myopia (OR, 1.78; 95% CI, 1.44-2.20), and baseline presence of any cataract, including nuclear cataract (OR, 3.78; 95% CI, 2.91-4.89), cortical cataract (OR, 3.01; 95% CI, 2.45-3.71), and posterior subcapsular cataract (OR, 5.00; 95% CI, 3.91-6.41). The population attributable risks of cataract surgery related to diabetes and myopia were 17.6% and 19.1%, respectively. CONCLUSIONS: One in 10 Malay, Indian, and Chinese Singaporeans 40 years of age or older underwent cataract surgery in at least 1 eye over 6 years. In Asian populations, diabetes and myopia, 2 well-known factors associated with cataract prevalence, are significant and potentially modifiable factors associated with the need for cataract surgery.

The future burden of lung cancer attributable to current modifiable behaviours: a pooled study of seven Australian cohorts.

Background: Knowledge of preventable disease and differences in disease burden can inform public health action to improve health and health equity. We quantified the future lung cancer burden preventable by behavioural modifications across Australia. Methods: We pooled seven Australian cohort studies (n = 367 058) and linked them to national registries to identify lung cancers and deaths. We estimated population attributable fractions and their 95% confidence intervals (CIs) for modifiable risk factors, using risk estimates from the cohort data and risk factor exposure distribution from contemporary national health surveys. Results: During the first 10-year follow-up, there were 2025 incident lung cancers and 20 349 deaths. Stopping current smoking could prevent 53.7% (95% CI, 50.0-57.2%) of lung cancers over 40 years and 18.3% (11.0-25.1%) in 10 years. The smoking-attributable burden is highest in males, those who smoke <20 cigarettes per day, are <75 years of age, unmarried, of lower educational attainment, live in remote areas or are healthy weight. Increasing physical activity and fruit consumption, if causal, could prevent 15.6% (6.9-23.4%) and 7.5% (1.3-13.3%) of the lung cancer burden, respectively. Jointly, the three behaviour modifications could prevent up to 63.0% (58.0-67.5%) of lung cancers in 40 years, and 31.2% (20.9-40.1%) or 43 300 cancers in 10 years. The preventable burden is highest among those with multiple risk factors. Conclusions: Smoking remains responsible for the highest burden of lung cancer in Australia. The uneven burden distribution distinguishes subgroups that could benefit the most from activities to control the world's deadliest cancer.