Melbourne School of Population and Global Health - Research Publications
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ItemDNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies(WILEY, 2018-04-15)The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them "age acceleration." We aimed to assess the associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B-cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15-30% for the fourth versus first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.
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ItemLifetime alcohol intake and risk of non-Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study(WILEY, 2018-03-01)Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 37,990 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value = 0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value = 0.05), 1.03 (95% CI: 0.94-1.12; p value = 0.6), and 1.06 (95% CI: 0.83-1.37; p value = 0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low-drinking cohort, we did not detect a dose-dependent association between lifetime alcohol intake and NHL risk.
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ItemAssociations of alcohol intake, smoking, physical activity and obesity with survival following colorectal cancer diagnosis by stage, anatomic site and tumor molecular subtype(WILEY, 2018-01-15)The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-1994) and wave 2 (2003-2007). We included participants diagnosed to 31 August 2015 with incident stages I-III CRC within 10-years post exposure assessment. Information on tumor characteristics and vital status was obtained. Tumor DNA was tested for microsatellite instability (MSI) and somatic mutations in oncogenes BRAF (V600E) and KRAS. We estimated hazard ratios (HRs) for associations between lifestyle factors and overall and CRC-specific mortality using Cox regression. Of 724 eligible CRC cases, 339 died (170 from CRC) during follow-up (average 9.0 years). Exercise (non-occupational/leisure-time) was associated with higher CRC-specific survival for stage II (HR = 0.25, 95% CI: 0.10-0.60) but not stages I/III disease (p for interaction = 0.01), and possibly for colon and KRAS wild-type tumors. Waist circumference was inversely associated with CRC-specific survival (HR = 1.25 per 10 cm increment, 95% CI: 1.08-1.44), independent of stage, anatomic site and tumor molecular status. Cigarette smoking was associated with lower overall survival, with suggestive evidence of worse survival for BRAF mutated CRC, but not with CRC-specific survival. Alcohol intake was not associated with survival. Survival did not differ by MSI status. We have identified pre-diagnostic predictors of survival following CRC that may have clinical and public health relevance.
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ItemLifetime alcohol intake is associated with an increased risk of KRAS plus and BRAF-/KRAS- but not BRAF plus colorectal cancer(WILEY, 2017-04)Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway.
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ItemAssociation between selected dietary scores and the risk of urothelial cell carcinoma: A prospective cohort study(WILEY, 2016-09-15)Studies investigating the association of food and nutrient consumption with the risk of urothelial cell carcinoma (UCC) have produced mixed results. We used three common dietary scores, the Mediterranean Diet Score (MDS), the Alternate Healthy Eating Index 2010 (AHEI-2010) and the Dietary Inflammatory Index (DII) to assess the evidence of an association between diet and the risk of UCC. Over a median follow-up time of 21.3 years, 379 incident UCC cases were diagnosed. Dietary scores were calculated using data from a 121-item food frequency questionnaire administered at baseline. We used Cox models to compute hazard ratios (HR) for the association between dietary scores (per one standard deviation) and UCC risk. In order to reflect overall adherence to a healthy diet, a metascore was constructed by summing the quintiles of each of the three scores. None of the dietary scores was associated with the risk of UCC overall. A healthier diet was found to be inversely associated with the risk of invasive (MDS: HR = 0.86, 95% CI: 0.74-1.00, metascore: HR = 0.84, 95% CI: 0.71-0.98), but not superficial disease (heterogeneity between subtypes p = 0.04 and p = 0.03, respectively). Results were consistent but weaker for the DII and the AHEI-2010. We found some evidence of effect modification by smoking, in particular for the metascore (Current: HR = 0.77, 95% CI: 0.58-1.01, Former: HR = 0.77, 95% CI: 0.64-0.92, Never: HR = 1.01, 95% CI: 0.81-1.26, p for heterogeneity = 0.05). A healthy diet may be protective against the risk of invasive, but not superficial, UCC. Promoting healthy dietary habits may help lower the risk of invasive UCC, especially for current and former smokers.
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ItemHome-based HPV self-sampling improves participation by never-screened and under-screened women: Results from a large randomized trial (iPap) in Australia(WILEY-BLACKWELL, 2016-07-15)We conducted a randomized controlled trial to determine whether HPV self-sampling increases participation in cervical screening by never- and under-screened (not screened in past 5 years) women when compared with a reminder letter for a Pap test. Never- or under-screened Victorian women aged 30-69 years, not pregnant and with no prior hysterectomy were eligible. Within each stratum (never-screened and under-screened), we randomly allocated 7,140 women to self-sampling and 1,020 to Pap test reminders. The self-sampling kit comprised a nylon tipped flocked swab enclosed in a dry plastic tube. The primary outcome was participation, as indicated by returning a swab or undergoing a Pap test; the secondary outcome, for women in the self-sampling arm with a positive HPV test, was undergoing appropriate clinical investigation. The Roche Cobas® 4800 test was used to measure presence of HPV DNA. Participation was higher for the self-sampling arm: 20.3 versus 6.0% for never-screened women (absolute difference 14.4%, 95% CI: 12.6-16.1%, p < 0.001) and 11.5 versus 6.4% for under-screened women (difference 5.1%, 95% CI: 3.4-6.8%, p < 0.001). Of the 1,649 women who returned a swab, 45 (2.7%) were positive for HPV16/18 and 95 (5.8%) were positive for other high-risk HPV types. Within 6 months, 28 (62.2%) women positive for HPV16/18 had colposcopy as recommended and nine (20%) had cytology only. Of women positive for other high-risk HPV types, 78 (82.1%) had a Pap test as recommended. HPV self-sampling improves participation in cervical screening for never- and under-screened women and most women with HPV detected have appropriate clinical investigation.
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ItemA randomized controlled trial of a wearable technology-based intervention for increasing moderate to vigorous physical activity and reducing sedentary behavior in breast cancer survivors: The ACTIVATE Trial(WILEY, 2019-08-15)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.
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ItemMaintenance of physical activity and sedentary behavior change, and physical activity and sedentary behavior change after an abridged intervention: Secondary outcomes from the ACTIVATE Trial(WILEY, 2019-08-15)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.
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ItemRural-urban residence and cancer survival in high-income countries: A systematic review(WILEY, 2019-07-01)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.