Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 347
Filtrar
1.
EJHaem ; 3(1): 109-120, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846225

RESUMO

Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case-control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales. Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50-0.93), and there was an inverse dose-response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% CI: 0.86-0.99); there was no evidence of an interaction with sex. There was no evidence of an association with MM risk for smoking-related exposures (p > 0.18). The associations between smoking and alcohol with MM are similar to those with non-Hodgkin lymphoma. Further research into potential underlying mechanisms is warranted.

2.
Br J Dermatol ; 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35789991

RESUMO

BACKGROUND: Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D. OBJECTIVES: To examine the effect of vitamin D supplementation on the risk of developing KC. METHODS: We used data from the D-Health Trial, a randomized placebo-controlled trial of vitamin D supplementation (60 000 international units monthly for 5 years) among Australians aged ≥60 years. KC outcomes were captured through linkage to a national administrative dataset for those who consented (N = 20 334; 95%). We used negative binomial regression to analyse the incidence of KC excisions and the incidence of actinic lesions treated using cryotherapy or serial curettage, and flexible parametric survival models for analysis of time to first KC excision. RESULTS: Randomization to vitamin D supplementation did not reduce the incidence of KC lesions treated by excision [incidence rate ratio (IRR) 1·04; 95% confidence interval (CI) 0·98-1·11], the incidence of actinic lesions treated using other methods (IRR 1·01; 95% CI 0·95-1·08) or time to first histologically confirmed KC excision (hazard ratio 1·02; 95% CI 0·97-1·08). However, in subgroup analysis vitamin D increased the incidence of KC excisions in adults aged ≥ 70 years (IRR 1·13, 95% CI 1·04-1·23; P-value for interaction = 0·01). CONCLUSIONS: Vitamin D supplementation did not reduce the incidence of KC or other actinic lesions. What is already known about this topic? Laboratory studies have suggested possible protective effects of vitamin D on skin cancer. Observational studies investigating the association between vitamin D and risk of keratinocyte cancer are largely uninformative as ultraviolet radiation both causes skin cancer and is the primary source of vitamin D. The evidence from randomized controlled trials of vitamin D is limited and inconclusive. What does this study add? This population-based, randomized controlled trial suggests that supplementing older adults with a high monthly dose of vitamin D for 5 years does not affect the incidence of keratinocyte cancer.

3.
J Infect Dis ; 226(6): 949-957, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-35780325

RESUMO

BACKGROUND: Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection. METHODS: The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60-84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years. For this analysis, the primary outcome was the number of antibiotic prescription episodes; secondary outcomes were total number of prescriptions, repeat prescription episodes, and antibiotics for urinary tract infection. We estimated incidence rate ratios (IRRs) using negative binomial regression, and odds ratios using logistic regression. RESULTS: Vitamin D supplementation slightly reduced the number of prescription episodes (IRR, 0.98; 95% confidence interval [CI], .95-1.01), total prescriptions (IRR, 0.97; 95% CI, .93-1.00), and repeat prescription episodes (IRR, 0.96; 95% CI, .93-1.00). There was stronger evidence of benefit in people predicted to have insufficient vitamin D at baseline (prescription episodes IRR, 0.93; 95% CI, .87-.99). CONCLUSIONS: Vitamin D may reduce the number of antibiotic prescriptions, particularly in people with low vitamin D status. This supports the hypothesis that vitamin D has a clinically relevant effect on the immune system. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.


Assuntos
Antibacterianos , Suplementos Nutricionais , Adulto , Idoso , Antibacterianos/uso terapêutico , Austrália/epidemiologia , Colecalciferol/uso terapêutico , Humanos , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico
4.
Br J Nutr ; : 1-28, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35837679

RESUMO

Barrett's oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case-control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages, and dietary scores, on risk of BE in over 20,000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990-94) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007-10). Logistic regression models were used to estimate odds ratios [ORs] and 95% confidence intervals [CIs] for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest versus lowest quartile: OR=0.59; CI: 0.38-0.94; p-trend=0.02 and OR=0.58; CI: 0.37-0.93; p-trend=0.02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR=1.54; CI: 0.97-2.44; p-trend=0.04) and total fat intake (OR per 10g/d=1.11; CI: 1.00-1.23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy, or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.

5.
Epigenetics ; : 1-10, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35726372

RESUMO

Lifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N = 7,431) and validation (N = 4,307) samples. Using paired genetic-methylation data (N = 4,307), gene-environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), alcohol consumption (459 CpGs), and BMI (85 CpGs) and 2) two epigenetic ageing measures, PhenoAge and GrimAge. In the validation sample, PGS explained ~1.4% (P = 1 × 10-14), ~0.6% (P = 2 × 10-7), and ~8.7% (P = 7 × 10-87) of variance in smoking initiation, alcohol consumption, and BMI, respectively. Nominally significant interaction effects (P < 0.05) were found at 61, 14, and 7 CpGs for smoking, alcohol consumption, and BMI, respectively. There was strong evidence that all lifestyle-related phenotypes were positively associated with PhenoAge and GrimAge, except for alcohol consumption with PhenoAge. There was weak evidence that the association of smoking with GrimAge was attenuated in participants genetically predisposed to smoking (interaction term: -0.022, standard error [SE] = 0.012, P = 0.058) and that the association of alcohol consumption with PhenoAge was attenuated in those genetically predisposed to drink alcohol (interaction term: -0.030, SE = 0.015, P = 0.041). In conclusion, genetic susceptibility to unhealthy lifestyles did not strongly modify the association between observed lifestyle behaviour and blood DNA methylation. Potential associations were observed for epigenetic ageing measures, which should be replicated in additional studies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35654416

RESUMO

BACKGROUND: Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's oesophagus (BE) are incompletely understood and might differ by sex. METHODS: In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 BE cases (identified at 2007-10 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-94). To explore possible mechanisms, we 1) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and 2) quantified the effect of H. pylori seronegativity on BE mediated by GERD using causal mediation analysis. RESULTS: For men, H. pylori seronegativity was associated with 1.69-fold (CI:1.03-2.75) and 2.28-fold (CI:1.27-4.12) higher odds of GERD and BE, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; p=0.015). For men, 5 of the 15 per 1,000 excess BE risk from being seronegative was mediated by GERD. CONCLUSIONS: Men, but not women, who were H. pylori seronegative had increased risks of GERD and BE. A possible explanation might be sex-differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on BE risk among men supports this proposed mechanism. IMPACT: The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and BE in future studies.

8.
J Med Screen ; 29(3): 185-193, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35313763

RESUMO

OBJECTIVES: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds. SETTING: The randomised controlled trial was conducted in Australia. METHODS: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed. RESULTS: The first round of HPV self-sampling kits were mailed from May-July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1-89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000). CONCLUSION: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Austrália/epidemiologia , Detecção Precoce de Câncer , Feminino , Seguimentos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Programas de Rastreamento , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Autocuidado , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal
9.
Int J Behav Nutr Phys Act ; 19(1): 30, 2022 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305675

RESUMO

BACKGROUND: Higher levels of time spent sitting (sedentary behavior) contribute to adverse health outcomes, including earlier death. This effect may be modified by other lifestyle factors. We examined the association of television viewing (TV), a common leisure-time sedentary behavior, with all-cause mortality, and whether this is modified by body mass index (BMI), physical activity, smoking, alcohol intake, soft drink consumption, or diet-associated inflammation. METHODS: Using data from participants in the Melbourne Collaborative Cohort Study, flexible parametric survival models assessed the time-dependent association of self-reported TV time (three categories: < 2 h/day, 2-3 h/day, > 3 h/day) with all-cause mortality. Interaction terms were fitted to test whether there was effect modification of TV time by the other risk factors. RESULTS: From 19,570 participants, 4,417 deaths were reported over a median follow up of 14.5 years. More TV time was associated with earlier mortality; however, this relationship diminished with increasing age. The hazard ratio (HR) and 95% confidence interval (95% CI) for > 3 h/day compared with < 2 h/day of TV time was 1.34 (1.16, 1.55) at 70 years, 1.14 (1.04, 1.23) at 80 years, and 0.95 (0.84, 1.06) at 90 years. The TV time/mortality relationship was more evident in participants who were physically inactive (compared with active; p for interaction < 0.01) or had a higher dietary inflammatory index score (compared with a lower score; p for interaction = 0.03). No interactions were detected between TV time and BMI, smoking, alcohol intake, nor soft-drink consumption (all p for interaction > 0.16). CONCLUSIONS: The relationship between TV time and all-cause mortality may change with age. It may also be more pronounced in those who are otherwise inactive or who have a pro-inflammatory diet.


Assuntos
Exercício Físico , Televisão , Índice de Massa Corporal , Estudos de Coortes , Humanos , Fumar
10.
Int J Cancer ; 151(1): 56-66, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35182083

RESUMO

We examined associations between sex-specific alcohol intake trajectories and alcohol-related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10-year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage-specific frequency and quantity, was used to estimate group-based sex-specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol-related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol-related cancers were diagnosed during 485 525 person-years in women and 789 during 303 218 person-years in men. For men, compared with lifetime abstention, heavy intake (mean ≥ 60 g/day) at age 20 to 39 followed by either an early (from age 40 to 49) (early decreasing heavy; HR = 1.75, 95% CI: 1.25-2.44) or late decrease (from age 60 to 69) (late decreasing heavy; HR = 1.94, 95% CI: 1.28-2.93), and moderate intake (mean <60 g/day) at age 20 to 39 increasing to heavy intake in middle-age (increasing heavy; HR = 1.45, 95% CI: 1.06-1.97) were associated with increased risk of alcohol-related cancer. For women, compared with lifetime abstention, increasing intake from age 20 (increasing moderate) was associated with increased alcohol-related cancer risk (HR = 1.25, 95% CI: 1.06-1.48). Similar associations were observed for colorectal (men) and breast cancer. Heavy drinking during early adulthood might increase cancer risk later in life.


Assuntos
Neoplasias da Mama , Acontecimentos que Mudam a Vida , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
11.
Lancet Diabetes Endocrinol ; 10(2): 120-128, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35026158

RESUMO

BACKGROUND: The effect of supplementing unscreened adults with vitamin D3 on mortality is unclear. We aimed to determine whether monthly doses of vitamin D3 influenced mortality in older Australians. METHODS: We did a randomised, double-blind, placebo-controlled trial of oral vitamin D3 supplementation (60 000 IU per month) in Australians 60 years or older who were recruited across the country via the Commonwealth electoral roll. Participants were randomly assigned (1:1), using automated computer-generated permuted block randomisation, to receive one oral gel capsule of either 60 000 IU vitamin D3 or placebo once a month for 5 years. Participants, staff, and investigators were blinded to study group allocation. The primary endpoint was all-cause mortality assessed in all participants who were randomly assigned. We also analysed mortality from cancer, cardiovascular disease, and other causes. Hazard ratios (HRs) and 95% CIs were generated using flexible parametric survival models. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763. FINDINGS: Between Feb 14, 2014, and June 17, 2015, we randomly assigned 21 315 participants, including 10 662 to the vitamin D group and 10 653 to the placebo group. In 4441 blood samples collected from randomly sampled participants (N=3943) during follow-up, mean serum 25-hydroxy-vitamin D concentrations were 77 (SD 25) in the placebo group and 115 (SD 30) nmol/L in the vitamin D group. Following 5 years of intervention (median follow-up 5·7 years [IQR 5·4-6·7]), 1100 deaths were recorded (placebo 538 [5·1%]; vitamin D 562 [5·3%]). 10 661 participants in the vitamin D group and 10 649 participants in the placebo group were included in the primary analysis. Five participants (one in the vitamin D group and four in the placebo group) were not included as they requested to be withdrawn and their data to be destroyed. The HR of vitamin D3 effect on all-cause mortality was 1.04 [95% CI 0·93 to 1·18]; p=0·47)and the HR of vitamin D3 effect on cardiovascular disease mortality was 0·96 (95% CI 0·72 to 1·28; p=0·77). The HR for cancer mortality was 1·15 (95% CI 0·96 to 1·39; p=0·13) and for mortality from other causes it was 0·83 (95% CI 0·65 to 1·07; p=0·15). The odds ratio for the per-protocol analysis was OR 1·18 (95% CI 1·00 to 1·40; p=0·06). In exploratory analyses excluding the first 2 years of follow-up, those randomly assigned to receive vitamin D had a numerically higher hazard of cancer mortality than those in the placebo group (HR 1·24 [95% CI 1·01-1·54]; p=0·05). INTERPRETATION: Administering vitamin D3 monthly to unscreened older people did not reduce all-cause mortality. Point estimates and exploratory analyses excluding the early follow-up period were consistent with an increased risk of death from cancer. Pending further evidence, the precautionary principle would suggest that this dosing regimen might not be appropriate in people who are vitamin D-replete. FUNDING: The D-Health Trial is funded by National Health and Medical Research Council.


Assuntos
Doenças Cardiovasculares , Adulto , Idoso , Austrália/epidemiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Vitamina D , Vitaminas/uso terapêutico
12.
Cancer Med ; 11(4): 1145-1159, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048536

RESUMO

BACKGROUND: Mechanisms underlying the adiposity-cancer relationship are incompletely understood. We quantified the mediating roles of C-reactive protein (CRP), leptin, fasting insulin, and estradiol in the effect of adiposity on estrogen receptor (ER)-positive breast, endometrial, and colorectal cancer risk in postmenopausal women. METHODS: We used a case-cohort study within the Women's Health Initiative Observational Study, analyzed as a cumulative sampling case-control study. The study included 188 breast cancer cases, 98 endometrial cancer cases, 193 colorectal cancer cases, and 285 controls. Interventional indirect and direct effects on the risk ratio (RR) scale were estimated using causal mediation analysis. RESULTS: For breast cancer, the total effect RR for BMI ≥30 versus ≥18.5-<25 kg/m2 was 1.87 (95%CI,1.11-3.13). The indirect effect RRs were 1.38 (0.79-2.33) through leptin and CRP, 1.58 (1.17-2.43) through insulin, and 1.11 (0.98-1.30) through estradiol. The direct effect RR was 0.82 (0.39-1.68). For endometrial cancer, the total effect RR was 2.12 (1.12-4.00). The indirect effect RRs were 1.72 (0.85-3.98) through leptin and CRP, 1.42 (0.96-2.26) through insulin, and 1.24 (1.03-1.65) through estradiol. The direct effect RR was 0.70 (0.23-2.04). For colorectal cancer, the total effect RR was 1.70 (1.03-2.79). The indirect effect RRs were 1.04 (0.61-1.72) through leptin and CRP, 1.36 (1.00-1.88) through insulin, and 1.02 (0.88-1.17) through estradiol. The direct effect RR was 1.16 (0.58-2.43). CONCLUSION: Leptin, CRP, fasting insulin, and estradiol appear to mediate the effect of high BMI on cancer risk to different extents, with likely varying degrees of importance between cancers. These insights might be important in developing interventions to modify obesity-associated cancer risk in postmenopausal women.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Neoplasias do Endométrio , Adiposidade , Índice de Massa Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/etiologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Estradiol , Jejum , Feminino , Humanos , Insulina/metabolismo , Leptina , Obesidade/complicações , Pós-Menopausa , Fatores de Risco
14.
J Gerontol A Biol Sci Med Sci ; 77(4): 826-836, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34117761

RESUMO

BACKGROUND: Inflammation is a key feature of aging. We aimed to (i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality and (ii) develop a signature of "inflammaging." METHODS: Thirty-four blood markers relating to inflammation, B vitamin status, and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age = 59 years) and follow-up (median age = 70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with 2 marker scores calculated across all markers associated with age and mortality, respectively. RESULTS: The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5'-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24-1.57, p = 2 × 10-8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23-1.55, p = 4 × 10-8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28-1.60, p = 1 × 10-10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. CONCLUSION: Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on 10 markers was strongly associated with mortality.


Assuntos
Complexo Vitamínico B , Idoso , Biomarcadores , Estudos de Coortes , Humanos , Inflamação , Cinurenina/metabolismo
15.
Dis Esophagus ; 35(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34409990

RESUMO

We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.


Assuntos
Esôfago de Barrett , Refluxo Gastroesofágico , Austrália/epidemiologia , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Humanos , Incidência , Estilo de Vida , Masculino , Fatores de Risco
16.
Int J Epidemiol ; 51(2): 641-667, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-34480556

RESUMO

BACKGROUND: Questions remain about the effect on mortality of physical activity and sedentary behaviour over time. We summarized the evidence from studies that assessed exposure from multiple time points and critiqued the analytic approaches used. METHODS: A search was performed on MEDLINE, Embase, Emcare, Scopus and Web of Science up to January 2021 for studies of repeatedly assessed physical activity or sedentary behaviour in relation to all-cause or cause-specific mortality. Relative risks from individual studies were extracted. Each study was assessed for risk of bias from multiple domains. RESULTS: We identified 64 eligible studies (57 on physical activity, 6 on sedentary behaviour, 1 on both). Cox regression with a time-fixed exposure history (n = 45) or time-varying covariates (n = 13) were the most frequently used methods. Only four studies used g-methods, which are designed to adjust for time-varying confounding. Risk of bias arose primarily from inadequate adjustment for time-varying confounders, participant selection, exposure classification and changes from measured exposure. Despite heterogeneity in methods, most studies found that being consistently or increasingly active over adulthood was associated with lower all-cause and cardiovascular-disease mortality compared with being always inactive. Few studies examined physical-activity changes and cancer mortality or effects of sedentary-behaviour changes on mortality outcomes. CONCLUSIONS: Accumulating more evidence using longitudinal data while addressing the methodological challenges would provide greater insight into the health effects of initiating or maintaining a more active and less sedentary lifestyle.


Assuntos
Doenças Cardiovasculares , Comportamento Sedentário , Adulto , Viés , Causas de Morte , Exercício Físico , Humanos
17.
Cancer Epidemiol Biomarkers Prev ; 31(1): 16-27, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34670800

RESUMO

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28.


Assuntos
Neoplasias da Mama/prevenção & controle , Exercício Físico , Hormônios Esteroides Gonadais/sangue , Causalidade , Feminino , Humanos , Fatores de Risco
18.
Cancer Epidemiol Biomarkers Prev ; 31(1): 28-37, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34670801

RESUMO

We undertook a systematic review and appraised the evidence for an effect of circulating sex steroid hormones and sex hormone-binding globulin (SHBG) on breast cancer risk in pre- and postmenopausal women. Systematic searches identified prospective studies relevant to this review. Meta-analyses estimated breast cancer risk for women with the highest compared with the lowest level of sex hormones, and the DRMETA Stata package was used to graphically represent the shape of these associations. The ROBINS-E tool assessed risk of bias, and the GRADE system appraised the strength of evidence. In premenopausal women, there was little evidence that estrogens, progesterone, or SHBG were associated with breast cancer risk, whereas androgens showed a positive association. In postmenopausal women, higher estrogens and androgens were associated with an increase in breast cancer risk, whereas higher SHBG was inversely associated with risk. The strength of the evidence quality ranged from low to high for each hormone. Dose-response relationships between sex steroid hormone concentrations and breast cancer risk were most notable for postmenopausal women. These data support the plausibility of a role for sex steroid hormones in mediating the causal relationship between physical activity and the risk of breast cancer.See related reviews by Lynch et al., p. 11 and Swain et al., p. 16.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Exercício Físico , Feminino , Hormônios Esteroides Gonadais , Humanos , Pré-Menopausa , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual
19.
Cancer Epidemiol Biomarkers Prev ; 31(1): 11-15, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34670802

RESUMO

Epidemiologic research suggests that physical activity is associated with a reduced risk of breast cancer, but the causal nature of this link is not clear. Investigating mechanistic pathways can provide evidence of biological plausibility and improve causal inference. This project will examine three putative pathways (sex steroid hormones, insulin signaling, and inflammation) in a series of two-stage systematic reviews. Stage 1 used Text Mining for Mechanism Prioritisation (TeMMPo) to identify and prioritize relevant biological intermediates. Stage 2 will systematically review the findings from studies of (i) physical activity and intermediates and (ii) intermediates and breast cancer. Ovid MEDLINE, EMBASE, and SPORTDiscus will be searched using a combination of subject headings and free-text terms. Human intervention and prospective, observational studies will be eligible for inclusion. Meta-analysis will be performed where possible. Risk of bias will be assessed using the Cochrane Collaboration tool, or the ROBINS-I or ROBINS-E tool, depending on study type. Strength of evidence will be assessed using the GRADE system. In addition to synthesizing the mechanistic evidence that links physical activity with breast cancer risk, this project may also identify priority areas for future research and help inform the design and implementation of physical activity interventions.See related reviews by Swain et al., p. 16 and Drummond et al., p. 28.


Assuntos
Neoplasias da Mama/prevenção & controle , Exercício Físico , Causalidade , Mineração de Dados , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Inflamação/sangue , Insulina/sangue , Projetos de Pesquisa
20.
BMC Musculoskelet Disord ; 22(1): 887, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666727

RESUMO

BACKGROUND: To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study. METHODS: This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders. RESULTS: Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women. CONCLUSIONS: Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis.


Assuntos
Artroplastia de Quadril , Osteoartrite do Quadril , Artroplastia de Quadril/efeitos adversos , Austrália/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Quadril/cirurgia , Estudos Prospectivos , Fatores de Risco , Vitamina D/análogos & derivados
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...