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1.
BMJ Open ; 9(8): e030078, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401610

RESUMO

OBJECTIVE: Limited research has assessed the association between patterns of body mass index (BMI) change across adulthood and mortality. We aimed to identify groups of individuals who followed specific group-based BMI trajectories across adulthood, using weight collected on three occasions and recalled data from early adulthood, and to examine associations with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Melbourne, Australia. PARTICIPANTS: Adults (n=29 881) enrolled in the Melbourne Collaborative Cohort Study, who were aged from 40 to 70 years between 1990 and 1994, and had BMI data for at least three time points. OUTCOME: Deaths from any cause before 31 March 2017 and deaths from obesity-related cancers, cardiovascular diseases (CVDs) and other causes before 31 December 2013. RESULTS: We identified six group-based BMI trajectories: lower-normal stable (TR1), higher-normal stable (TR2), normal to overweight (TR3), chronic borderline obesity (TR4), normal to class I obesity (TR5) and overweight to class II obesity (TR6). Generally, compared with maintaining lower-normal BMI throughout adulthood, the lowest mortality was experienced by participants who maintained higher-normal BMI (HR 0.90; 95% CI 0.84 to 0.97); obesity during midlife was associated with higher all-cause mortality even when BMI was normal in early adulthood (HR 1.09; 95% CI 0.98 to 1.21) and prolonged borderline obesity from early adulthood was also associated with elevated mortality (HR 1.16; 95% CI 1.01 to 1.33). These associations were stronger for never-smokers and for death due to obesity-related cancers. Being overweight in early adulthood and becoming class II obese was associated with higher CVD mortality relative to maintaining lower-normal BMI (HR 2.27; 95% CI 1.34 to 3.87). CONCLUSION: Our findings highlight the importance of weight management throughout adulthood to reduce mortality.

2.
Int J Cancer ; 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31187481

RESUMO

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.

3.
Breast Cancer Res ; 21(1): 62, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101124

RESUMO

BACKGROUND: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date. METHODS: We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis (< 50, ≥ 50), estrogen receptor (ER) status (+/-), and time since blood collection (< 5, 5-10, > 10 years). The false discovery rate (q value) was used to account for multiple testing. RESULTS: The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98). CONCLUSIONS: Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk.

4.
Int J Cancer ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.

5.
Clin Epigenetics ; 11(1): 66, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039828

RESUMO

BACKGROUND: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. METHODS: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. RESULTS: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. CONCLUSION: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.

6.
Cancer ; 125(16): 2856-2860, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31012968

RESUMO

BACKGROUND: This brief report examines the maintenance of moderate to vigorous physical activity (MVPA) and sedentary behavior changes approximately 12 weeks after the delivery of the ACTIVATE Trial primary intervention (use of the Garmin Vivofit 2 activity tracker coupled with a behavioral feedback and goal-setting session and 5 telephone-delivered health coaching sessions). We also examine the efficacy of an abridged intervention (use of the Garmin Vivofit 2 only) in the waitlist control group. METHODS: A pre-post design was employed to examine the secondary aims of the ACTIVATE Trial (n = 80; mean age = 62 years). MVPA and sedentary behavior were measured using Actigraph and activPAL accelerometers after delivery of the primary intervention (T2), and again 12 weeks later (T3). Linear mixed models with random effects were used to examine within-group changes in MVPA and sitting time variables. RESULTS: After the 12-week follow-up period, women in the primary intervention group had maintained their higher levels of MVPA (change from T2 to T3 = 14 min/wk; 95% CI = -18 to 46; P = .37). However, their sitting time increased slightly, by 7 min/d (95% CI = -20 to 34; P = .58), but it did not return to its preintervention level. After receiving the Garmin Vivofit 2, the waitlist control group increased their MVPA by 33 min/wk (95% CI = 3-64; P = .03) and reduced their sitting time by 38 min/d (95% CI = -69 to -7; P = .02) over the same 12-week period. CONCLUSION: The secondary outcomes from the ACTIVATE Trial suggest that wearable technology may generate sustainable changes in MVPA and sitting time. Wearable technology alone may be sufficient to change behavior, at least in the short term.

7.
Cancer ; 125(16): 2846-2855, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31012970

RESUMO

BACKGROUND: The benefits of an active lifestyle after a breast cancer diagnosis are well recognized, but the majority of survivors are insufficiently active. The ACTIVATE Trial examined the efficacy of an intervention (use of the Garmin Vivofit 2 activity monitor coupled with a behavioral feedback and goal-setting session and 5 telephone-delivered health coaching sessions) to increase moderate to vigorous physical activity (MVPA) and reduce sedentary behavior in breast cancer survivors. METHODS: This randomized controlled trial recruited 83 inactive, postmenopausal women diagnosed with stage I-III breast cancer who had completed primary treatment. Participants were randomly assigned to the intervention group or to the control group, and the intervention was delivered over a 12-week period. MVPA and sedentary behavior were measured with Actigraph and activPAL accelerometers at baseline (T1) and at the end of the intervention (T2). RESULTS: Retention in the trial was high, with 80 (96%) of participants completing T2 data collection. At T2, there was a significant between-group difference in MVPA (69 min/wk; 95% CI = 22-116) favoring the intervention group. The trial resulted in a statistically significant decrease in both total sitting time and prolonged bouts (≥20 min) of sitting, with between-group reductions of 37 min/d (95% CI = -72 to -2) and 42 min/d (95% CI = -83 to -2), respectively, favoring the intervention group. CONCLUSION: Results from the ACTIVATE Trial suggest that the use of wearable technology presents an inexpensive and scalable opportunity to facilitate more active lifestyles for cancer survivors. Whether or not such wearable technology-based interventions can create sustainable behavioral change should be the subject of future research.

8.
Cancer ; 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933318

RESUMO

There is some evidence that place of residence is associated with cancer survival, but the findings are inconsistent, and the underlying mechanisms by which residential location might affect survival are not well understood. We conducted a systematic review of observational studies investigating the association of rural versus urban residence with cancer survival in high-income countries. We searched the Ovid Medline, EMBASE, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases up to May 31, 2016. Forty-five studies published between 1984 and 2016 were included. We extracted unadjusted and adjusted relative risk estimates with the corresponding 95% confidence intervals. Most studies reported worse survival for cancer patients living in rural areas than those in urban regions. The most consistent evidence, observed across several studies, was for colorectal, lung, and prostate cancer. Of the included studies, 18 did not account for socio-economic position. Lower survival for more disadvantaged patients is well documented; therefore, it could be beneficial for future research to take socio-economic factors into consideration when assessing rural/urban differences in cancer survival. Some studies cited differential stage at diagnosis and treatment modalities as major contributing factors to regional inequalities in cancer survival. Further research is needed to disentangle the mediating effects of these factors, which may help to establish effective interventions to improve survival for patients living outside major cities.

9.
Int J Cancer ; 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30873591

RESUMO

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

10.
Nutr Cancer ; 71(4): 605-614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873873

RESUMO

Dietary intakes of B vitamins and other components involved in one-carbon metabolism, which is necessary for DNA replication, DNA repair, and regulation of gene expression, may be associated with carcinogenesis. We investigated associations between intakes of 11 nutrients (thiamine, riboflavin, niacin, pantothenic acid, vitamin B6, biotin, folate, vitamin B12, methionine, choline, and betaine) and gastric cancer risk. A total of 159 incident gastric cancer cases were identified from the Melbourne Collaborative Cohort Study (N = 41,513) and matched with 159 controls on year of birth, sex, and country of birth using incidence density sampling. Dietary intakes of nutrients were estimated at baseline (1990-1994) using a 121-item food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression models adjusting for Helicobacter pylori infection, and other potential confounders. We observed a positive association between intake of niacin and overall gastric cancer risk (OR = 1.33, 95%CI: 1.01-1.75 per SD increment). For thiamine, heterogeneity by subtype (cardia and non-cardia) was found (Phet = 0.05), with weak evidence of an inverse association with cardia cancer risk. Our results do not support increasing intakes of B vitamins or other nutrients involved in one-carbon metabolism to reduce gastric cancer risk in a well-nourished population.

11.
Cancer Epidemiol Biomarkers Prev ; 28(5): 900-908, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30842127

RESUMO

BACKGROUND: The role of vitamin D in cancer risk remains controversial, and limited data exist on associations between vitamin D and subtypes of specific cancers. We investigated associations between circulating 25-hydroxyvitamin D (25(OH)D) and risk of colorectal, breast, and prostate cancers, including subtypes. METHODS: A case-cohort study within the Melbourne Collaborative Cohort Study included 547 colorectal, 634 breast, and 824 prostate cancers, and a sex-stratified random sample of participants (n = 2,996). Concentration of 25(OH)D in baseline-dried blood spots was measured using LC-MS/MS. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for each cancer in relation to plasma-equivalent 25(OH)D concentration. Associations by stage and BRAF/KRAS status for colorectal cancer, estrogen receptor status for breast cancer, and aggressiveness for prostate cancer were examined in competing risks models. RESULTS: 25(OH)D concentrations were inversely associated with risk of colorectal cancer [highest vs. lowest 25(OH)D quintile: HR, 0.71; 95% confidence interval (CI), 0.51-0.98], which was limited to women (HR, 0.52; 95% CI, 0.33-0.82). Circulating 25(OH)D was also inversely associated with BRAF V600E-positive colorectal cancer (per 25 nmol/L increment: HR, 0.71; 95% CI, 0.50-1.01). There were no inverse associations with breast cancer (HR, 0.98; 95% CI, 0.70-1.36) or prostate cancer (HR, 1.11; 95% CI, 0.82-1.48). CONCLUSIONS: Circulating 25(OH)D concentration was inversely associated with colorectal cancer risk for women, but not with risk of breast cancer or prostate cancer. IMPACT: Vitamin D might play a role in preventing colorectal cancer. Further studies are required to confirm whether vitamin D is associated with specific tumor subtypes.

12.
PLoS One ; 14(3): e0214196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30913256

RESUMO

Homozygosity for the p.C282Y substitution in the HFE protein encoded by the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. McLaren et al. used bivariate mixture modeling to analyze the joint population distribution of transferrin saturation (TS) and serum ferritin concentration (SF) measured for participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. They identified four components (C1, C2, C3, and C4) with successively increasing means for TS and SF. They demonstrated that bivariate mixture modeling in TS and SF reflect the genetic locus of HFE and may isolate p.C282Y homozygotes from the general population. In the current study we used data from the another large cohort, the Australian HealthIron study of genetic and environmental modifiers of hereditary hemochromatosis, to validate the component analysis approach, to examine stability of component proportions over time and to determine if TS and SF values from an individual move between components at baseline and follow-up. Because sampling fractions from each p.C282Y / p.H63D genotype stratum are not equal, we used frequency weights based on the inverse of the probability of selection for invitation to participate. In the weighted female analytic cohorts, C4 captured most of C282Y homozygotes, and C2 was the largest component. We identified four components from the weighted male analytic cohort and C4 captured most of p.C282Y homozygotes. The bivariate mixture modeling approach suggested that the model is transferable from one white population to another, although estimated means within components may differ.

13.
Cancer Causes Control ; 30(4): 323-331, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798509

RESUMO

PURPOSE: Pancreatic cancer has one of the worst prognoses with 5-year survival below 10%. There is some evidence that alcohol consumption might increase the risk of pancreatic cancer. We examined associations of pre-diagnostic alcohol intake with (i) incidence of pancreatic cancer, and (ii) overall survival following pancreatic cancer. METHODS: Usual alcohol intake was estimated at recruitment in 1990-1994 for 38,472 participants in the Melbourne Collaborative Cohort Study using recalled frequency and quantity of beverage-specific intake for 10-year periods from age 20. Pancreatic cancer incidence (C25 according to International Classification of Diseases for Oncology) and vital status were ascertained through to 30 September 2015. Cox regression was performed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with lifetime, age 20-29, and baseline alcohol intakes. RESULTS: By the end of follow-up (average 20.2 years), 239 incident cases of pancreatic cancer were diagnosed, of which 228 had died. No evidence of an association was observed between alcohol intake and risk of pancreatic cancer. Higher lifetime alcohol intake was associated with lower overall survival following a diagnosis of pancreatic cancer (mortality HR 1.09 per 10 g/day increment, 95% CI 1.00-1.19; p value = 0.04). A similar finding was observed for age 20-29 intake (HR 1.09 per 10 g/day increment, 95% CI 1.02-1.18; p value = 0.01) but not with baseline intake. CONCLUSIONS: We observed an association between lower alcohol use from an early age and improved survival following pancreatic cancer, but this finding needs to be confirmed by other studies.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Bebidas , Neoplasias Pancreáticas/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
14.
Artigo em Inglês | MEDLINE | ID: mdl-30700025

RESUMO

Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.


Assuntos
Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Vitaminas/sangue , Estudos Observacionais como Assunto , Vitamina D/sangue
15.
Int J Cancer ; 145(7): 1768-1773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30694562

RESUMO

Age- and body mass index (BMI)-adjusted mammographic density is one of the strongest breast cancer risk factors. DNA methylation is a molecular mechanism that could underlie inter-individual variation in mammographic density. We aimed to investigate the association between breast cancer risk-predicting mammographic density measures and blood DNA methylation. For 436 women from the Australian Mammographic Density Twins and Sisters Study and 591 women from the Melbourne Collaborative Cohort Study, mammographic density (dense area, nondense area and percentage dense area) defined by the conventional brightness threshold was measured using the CUMULUS software, and peripheral blood DNA methylation was measured using the HumanMethylation450 (HM450) BeadChip assay. Associations between DNA methylation at >400,000 sites and mammographic density measures adjusted for age and BMI were assessed within each cohort and pooled using fixed-effect meta-analysis. Associations with methylation at genetic loci known to be associated with mammographic density were also examined. We found no genome-wide significant (p < 10-7 ) association for any mammographic density measure from the meta-analysis, or from the cohort-specific analyses. None of the 299 methylation sites located at genetic loci associated with mammographic density was associated with any mammographic density measure after adjusting for multiple testing (all p > 0.05/299 = 1.7 × 10-4 ). In summary, our study did not find evidence for associations between blood DNA methylation, as measured by the HM450 assay, and conventional mammographic density measures that predict breast cancer risk.

16.
Breast Cancer Res ; 20(1): 152, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545395

RESUMO

BACKGROUND: Case-control studies show that mammographic density is a better risk factor when defined at higher than conventional pixel-brightness thresholds. We asked if this applied to interval and/or screen-detected cancers. METHOD: We conducted a nested case-control study within the prospective Melbourne Collaborative Cohort Study including 168 women with interval and 422 with screen-detected breast cancers, and 498 and 1197 matched controls, respectively. We measured absolute and percent mammographic density using the Cumulus software at the conventional threshold (Cumulus) and two increasingly higher thresholds (Altocumulus and Cirrocumulus, respectively). Measures were transformed and adjusted for age and body mass index (BMI). Using conditional logistic regression and adjusting for BMI by age at mammogram, we estimated risk discrimination by the odds ratio per adjusted standard deviation (OPERA), calculated the area under the receiver operating characteristic curve (AUC) and compared nested models using the likelihood ratio criterion and models with the same number of parameters using the difference in Bayesian information criterion (ΔBIC). RESULTS: For interval cancer, there was very strong evidence that the association was best predicted by Cumulus as a percentage (OPERA = 2.33 (95% confidence interval (CI) 1.85-2.92); all ΔBIC > 14), and the association with BMI was independent of age at mammogram. After adjusting for percent Cumulus, no other measure was associated with risk (all P > 0.1). For screen-detected cancer, however, the associations were strongest for the absolute and percent Cirrocumulus measures (all ΔBIC > 6), and after adjusting for Cirrocumulus, no other measure was associated with risk (all P > 0.07). CONCLUSION: The amount of brighter areas is the best mammogram-based measure of screen-detected breast cancer risk, while the percentage of the breast covered by white or bright areas is the best mammogram-based measure of interval breast cancer risk, irrespective of BMI. Therefore, there are different features of mammographic images that give clinically important information about different outcomes.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Processamento de Imagem Assistida por Computador/métodos , Mamografia/métodos , Idoso , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Software
17.
Cancer Res ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425058

RESUMO

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.

18.
BMC Cancer ; 18(1): 1063, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390649

RESUMO

BACKGROUND: Physical activity reduces the risk of colorectal cancer (CRC), but the relevant evidence derives primarily from self-reported recreational and occupational activity. Less is known about the contribution of other domains of physical activity, such as transport and household. We examined associations between domain-specific physical activities and CRC risk within the Melbourne Collaborative Cohort Study. METHODS: Analyses included 23,586 participants who were free from invasive colorectal cancer and had completed the International Physical Activity Questionnaire-Long Form at follow-up 2 (2003-2007). Cox regression, with age as the time metric, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ordinal categories of each physical activity domain. RESULTS: Adjusted HRs for the highest versus the lowest categories of physical activity were 0.71 (95% CI: 0.51-0.98; ptrend = 0.03) for recreational activity; 0.80 (95% CI: 0.49-1.28; ptrend = 0.38) for occupational activity; 0.90 (95% CI: 0.68-1.19; ptrend = 0.20) for transport activity; and 1.07 (95% CI: 0.82-1.40; ptrend = 0.46) for household activity. CONCLUSIONS: Recreational activity was associated with reduced CRC risk. A non-significant, inverse association was observed for occupational activity, whereas no association was found for transport or household domains.

19.
Int J Cancer ; 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30318764

RESUMO

B-group vitamins, as components of the one carbon metabolism pathway, are involved in DNA synthesis, repair and methylation. Our aim was to investigate associations between circulating plasma levels of B vitamins and urothelial cell carcinoma (UCC). We conducted a nested case-control study of UCC within the Melbourne Collaborative Cohort Study. B vitamins were measured in pre-diagnostic plasma samples. Conditional logistic regression was used to estimate odds ratios (OR) for UCC risk associated with circulating B vitamins in 363 matched cases and controls. In a case-only analysis (N = 390), hazard ratios (HR) for overall survival associated with plasma B vitamins were estimated using Cox regression. There were no strong associations between UCC risk and pre-diagnostic levels of plasma B vitamins. No heterogeneity in UCC risk was observed by subtype (invasive or superficial), sex, smoking status or alcohol intake. There was no heterogeneity by country of birth for most B vitamins, except for folate (p-homogeneity = 0.03). In UCC cases, there were no strong associations between plasma B vitamins and overall survival. We found no associations between pre-diagnostic plasma concentrations of B-group vitamins and UCC risk or survival.

20.
Cancer Causes Control ; 29(11): 1071, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30311110

RESUMO

In the original publication of the article, the concluding paragraph of the Discussion section was inadvertently missed and is provided below.

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