Obesity increases the risk of 13 cancer types. Given the long process of carcinogenesis, it is important to determine the impact of patterns of body mass over time.
Using data from 30,377 ...participants in the Melbourne Collaborative Cohort Study, we identified body mass index (BMI) trajectories across adulthood and examined their association with the risk of obesity-related cancer. Participants completed interviews and questionnaires at baseline (1990-1994, age 40-69 years), follow-up 1 (1995-1998), and follow-up 2 (2003-2005). Body mass was recalled for age 18 to 21 years, measured at baseline, self-reported at follow-up 1, and measured at follow-up 2. Height was measured at baseline. Cancer diagnoses were ascertained from the Victorian Cancer Registry and the Australian Cancer Database. A latent class trajectory model was used to identify BMI trajectories that were not defined
. Cox regression was used to estimate HRs and 95% confidence intervals (CI) of obesity-related cancer risks by BMI trajectory.
Six distinct BMI trajectories were identified. Compared with people who maintained lower normal BMI, higher risks of developing obesity-related cancer were observed for participants who transitioned from normal to overweight (HR, 1.29; 95% CI, 1.13-1.47), normal to class I obesity (HR, 1.50; 95% CI, 1.28-1.75), or from overweight to class II obesity (HR, 1.66; 95% CI, 1.32-2.08).
Our findings suggest that maintaining a healthy BMI across the adult lifespan is important for cancer prevention.
Categorization of BMI by trajectory allowed us to identify specific risk groups to target with public health interventions.
Background
Cereal‐derived polyphenols have demonstrated protective mechanisms in colorectal cancer (CRC) models; however, confirmation in human studies is lacking. Therefore, this study examined the ...association between cereal polyphenol intakes and CRC risk in the Melbourne Collaborative Cohort Study (MCCS), a prospective cohort study in Melbourne, Australia that recruited participants between 1990 and 1994 to investigate diet–disease relationships.
Methods
Using food frequency questionnaire diet data matched to polyphenol data, dietary intakes of alkylresorcinols, phenolic acids, lignans, and total polyphenols from cereals were estimated. Hazard ratios (HRs) and 95% confidence intervals for CRC risk were estimated for quintiles of intake with the lowest quintile as the comparison category, using multivariable adjusted Cox proportional hazards models with age as the time axis adjusted for sex, socio‐economic status, alcohol consumption, fibre intake, country of birth, total energy intake, physical activity and smoking status.
Results
From 35,245 eligible adults, mean (SD) age 54.7 (8.6) years, mostly female (61%) and Australian‐born (69%), there were 1394 incident cases of CRC (946 colon cancers and 448 rectal cancers). Results for total cereal polyphenol intake showed reduced HRs in Q2 (HR: 0.80; 95% CI, 0.68–0.95) and Q4 (HR: 0.75; 95% CI, 0.62–0.90), and similar for phenolic acids. Alkylresorcinol intake showed reduced HR in Q3 (HR: 0.80; 95% CI, 0.67–0.95) and Q4 (HR: 0.79; 95% CI, 0.66–0.95).
Conclusions
Overall, the present study showed little evidence of association between intakes of cereal polyphenols and CRC risk. Future investigations may be useful to understand associations between cereal‐derived polyphenols and additional cancers in different populations.
Grains and cereals may offer chemoprotection in colorectal cancer (CRC), that may partly be attributed to polyphenols from cereal foods; however, populations studies are lacking. Utilising a cereal‐specific polyphenol database designed for a specific Australian cohort, survival analysis revealed limited association between cereal polyphenol intake and CRC risk. While the study findings are in general agreement with cohort studies from total foods, further comparative studies are needed.
Abstract
Background
We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a ...commercially available autoantibody biomarker test.
Methods
We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models’ sensitivity. All tests were 2-sided.
Results
The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval CI = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.
Conclusion
Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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 (P
het
= 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.
Using the Melbourne Collaborative Cohort Study, we examined the associations of occupation, household, transport, and leisure physical activity with pain interference with normal work and muscle pain ...after activity.
This cross-sectional analysis included 7655 working and 11,766 nonworking participants. Physical activity was assessed using the long-form International Physical Activity Questionnaire. Pain interference was assessed with the Short-Form 12-Item Health Survey version 2.0, and muscle pain after activity was assessed using the 12-item Somatic and Psychological Health Report. Ordered logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and restricted cubic splines were used to graphically represent the shape of associations.
All physical activity domain-pain outcome associations were nonlinear. Compared with participants who reported the lowest level of activity, participants who reported the median level of transport physical activity (10 MET·h·wk) reported less pain interference (workers: OR, 0.86 95% CI, 0.77-0.97; nonworkers: OR, 0.88 95% CI, 0.79-0.97) and muscle pain after activity (workers: OR, 0.81 95% CI, 0.70-0.95; nonworkers: OR, 0.86 95% CI, 0.77-0.95). Higher levels of leisure time activity (20 MET·h·wk) were associated with less pain interference in nonworkers (OR, 0.87; 95% CI, 0.77-0.98) and muscle pain after activity in workers (OR, 0.67; 95% CI, 0.56-0.80). Workers who reported the median level of household activity (16 MET·h·wk) had increased pain interference (OR, 1.19; 95% CI, 1.07-1.32) and muscle pain after activity (OR, 1.23; 95% CI, 1.06-1.42) than did those who reported the least household activity.
Associations between domain-specific physical activity and pain outcomes were not uniform. Within the transport and leisure domains, physical activity was inversely associated with pain-related outcomes, whereas household physical activity was positively associated with pain scores within the working sample.
The reliability of methylation measures from the widely used HumanMethylation450 (HM450K) microarray has not been assessed for DNA from dried blood spots (DBS) or peripheral blood mononuclear cells ...(PBMC), nor for combined data from different studies. Repeated HM450K methylation measures in DNA from DBS and PBMC samples were available from participants in six case-control studies nested within the Melbourne Collaborative Cohort Study. Reliability was assessed for individual CpGs by calculating the intraclass correlation coefficient (ICC) based on technical replicates (samples repeated in a single study; 126 PBMC, 136 DBS) and study duplicates (samples repeated across studies; 280 PBMC, 769 DBS) using mixed-effects models. Reliability based on technical replicates was moderate for PBMC (median ICC = 0.42), but lower for DBS (median ICC = 0.20). Study duplicates gave lower ICCs than technical replicates. CpGs that were either highly methylated or unmethylated generally had lower ICCs, which appeared to be mostly related to their lower variability. The ICCs for global methylation measures were high, typically greater than 0.70. The reliability of methylation measures determined by the HM450K microarray is wide-ranging and depends primarily on the variability in methylation at individual CpG sites. The power of association studies is low for a substantial proportion of CpGs in the HM450K assay.
Abstract
Background
Self-reported physical activity is inaccurate, yet few investigators attempt to adjust for measurement error when estimating risks for health outcomes. We estimated what the ...association between self-reported physical activity and colorectal cancer risk would be if physical activity had been assessed using accelerometry instead.
Methods
We conducted a validation study in which 235 Australian adults completed a telephone-administered International Physical Activity Questionnaire (IPAQ), and wore an accelerometer (Actigraph GT3X+) for 7 days. Using accelerometer-assessed physical activity as the criterion measure, we calculated validity coefficients and attenuation factors using a structural equation model adjusted for age, sex, education and body mass index. We then used a regression calibration approach to apply the attenuation factors to data from the Melbourne Collaborative Cohort Study (MCCS) to compute bias-adjusted hazard ratios (HR) and 95% confidence intervals (CI).
Results
Average daily minutes of physical activity from the short form of the International Physical Activity Questionnaire (IPAQ-short) were substantially higher than accelerometer-measured duration (55 versus 32 min). The validity coefficient (0.32; 95% CI: 0.20, 0.43) and attenuation factor (0.20; 95% CI: 0.12, 0.28) were low. The HRs for colorectal cancer risk for high (75th percentile; 411 min/week) versus low (25th percentile; 62 min/week) levels of self-reported physical activity were 0.95 (95% CI: 0.87, 1.05) before and 0.78 (95% CI: 0.47, 1.28) after bias adjustment.
Conclusions
Over-estimation of physical activity by the IPAQ-short substantially attenuates the association between physical activity and colorectal cancer risk, suggesting that the protective effect of physical activity has been previously underestimated.
Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction.
...Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples: 404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and 440 pairs from the Women's Health Initiative (WHI) cohort. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication data sets using the area under the curve (AUC).
The meta-analysis identified associations (
< 4.7 × 10
) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (
< 0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication data set in MCCS
= 134; odds ratio per SD (OR) = 1.37; 95% CI, 1.00-1.90 after confounder adjustment; AUC = 0.66, compared with AUC = 0.64 without methylation information. Limited evidence of replication was found in the second testing data set in WHI (
= 440; OR = 1.09; 95% CI, 0.91-1.30).
Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger data sets.
DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.
Men with prostate cancer experience side effects for which a supportive social environment may be beneficial. We examined the association between four measures of social connectedness and mortality ...after a prostate cancer diagnosis. Male participants in the Melbourne Collaborative Cohort Study in 1990–1994, who developed incident prostate cancer and attended follow‐up in 2003–2007, were eligible for the study. Information on social connectedness, collected at follow‐up, included (i) living arrangement; (ii) frequency of visits to friends/relatives and (iii) from friends/relatives; (iv) weekly hours of social activities. A total of 1,421 prostate cancer cases was observed (338 all‐cause deaths, 113 from prostate cancer), including 867 after follow‐up (150 all‐cause deaths, 55 from prostate cancer) and 554 before follow‐up (188 all‐cause deaths, 58 from prostate cancer). Cox models stratified by tumour Gleason score and stage, and sequentially adjusted for socioeconomic, health‐ and lifestyle‐related confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between social connectedness and all‐cause mortality after prostate cancer. Men who reported living alone before diagnosis had higher overall mortality (HR = 1.6, 95% CI: 1.0–2.5), after adjustment for socioeconomic, health and lifestyle confounders. Lower mortality was observed for men with more social activities (p‐trend = 0.07), but not in comprehensively adjusted models. Consistent with these findings, men living alone after prostate cancer diagnosis had higher mortality (HR = 1.3, 95% CI: 0.9–1.9). Lower mortality was observed with increasing socializing hours in the age‐adjusted model (p‐trend = 0.06) but not after more comprehensive adjustment. Our findings suggest that living with someone, but not other aspects of social connectedness, may be associated with decreased mortality for men with prostate cancer.
What's new?
Social support and interactions are associated with better health outcomes in general, but do they improve mortality rates for prostate cancer survivors? In this study, the authors found that survivors who lived alone did have substantially higher mortality than those who shared their home. No significant impact was observed, however, for other measures of social connectedness, such as visits with friends and relatives or time spent on social activities. Further research on specific factors that improve mortality in survivors who don't live alone is warranted.
To estimate the extent of measurement error in the Active Australia questionnaire, and to examine the impact of measurement error on the association of moderate-vigorous physical activity (MVPA) with ...obesity.
Accelerometer Validation Study, cross-sectional; data from the third wave of a prospective cohort (Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study)).
Self-reported physical activity data were obtained from 4005 participants of the third wave of the AusDiab study via the Active Australia questionnaire. Accelerometer-derived physical activity data were obtained from a subsample of 670 participants. Validity coefficients and attenuation factors were estimated from a measurement error model. A regression calibration method was applied to a logistic regression model examining the association between self-reported MVPA and obesity to adjust observed odds ratios (OR) for measurement error.
The validity coefficient was 0.35 (0.28, 0.43) and the attenuation factor was 0.16 (0.13, 0.20) in models adjusted for age and sex. The uncorrected OR for obesity for 210min/week of MVPA (50th percentile) relative to 80min/week (25th percentile) was 0.87 (0.85, 0.90). The attenuation factor was used to adjust this OR for measurement error, giving a corrected OR of 0.43 (0.32, 0.55).
Substantial measurement error (relative to accelerometry) was evident in the Active Australia questionnaire, leading to attenuation of the association of MVPA with obesity. A regression-calibration method can be used to adjust risk estimates for associations between self-reported MVPA and health-related outcomes for measurement error specific to self-report. These corrected risk estimates reflect associations that would be expected if MVPA were measured by accelerometry.
PDF
