Melbourne School of Population and Global Health - Research Publications
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ItemModifiable lifestyle risk factors and survival after diagnosis with multiple myeloma(TAYLOR & FRANCIS LTD, 2023-10-03)BACKGROUND: While remaining incurable, median overall survival for MM now exceeds 5 years. Yet few studies have investigated how modifiable lifestyle factors influence survival. We investigate whether adiposity, diet, alcohol, or smoking are associated with MM-related fatality. RESEARCH DESIGN AND METHODS: We recruited 760 incident cases of MM via cancer registries in two Australian states during 2010-2016. Participants returned questionnaires on health and lifestyle. Follow-up ended in 2020. Flexible parametric survival models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lifestyle exposures and risk of all-cause and MM-specific fatality. RESULTS: Higher pre-diagnosis Alternative Healthy Eating Index (AHEI) scores were associated with reduced MM-specific fatality (per 10-unit score, HR = 0.84, 95%CI = 0.70-0.99). Pre-diagnosis alcohol consumption was inversely associated with MM-specific fatality, compared with nondrinkers (0.1-20 g per day, HR = 0.59, 95%CI = 0.39-0.90; >20 g per day, HR = 0.67, 95%CI = 0.40-1.13). Tobacco smoking was associated with increased all-cause fatality compared with never smoking (former smokers: HR = 1.44, 95%CI = 1.10-1.88; current smokers: HR = 1.30, 95%CI = 0.80-2.10). There was no association between pre-enrollment body mass index (BMI) and MM-specific or all-cause fatality. CONCLUSIONS: Our findings support established recommendations for healthy diets and against smoking. Higher quality diet, as measured by the AHEI, may improve survival post diagnosis with MM.
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ItemAlcohol and tobacco use and risk of multiple myeloma: A case‐control study(Wiley, 2022-02)Abstract 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.
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ItemProspective Evaluation over 15 Years of Six Breast Cancer Risk Models(MDPI, 2021-10)Prospective validation of risk models is needed to assess their clinical utility, particularly over the longer term. We evaluated the performance of six commonly used breast cancer risk models (IBIS, BOADICEA, BRCAPRO, BRCAPRO-BCRAT, BCRAT, and iCARE-lit). 15-year risk scores were estimated using lifestyle factors and family history measures from 7608 women in the Melbourne Collaborative Cohort Study who were aged 50-65 years and unaffected at commencement of follow-up two (conducted in 2003-2007), of whom 351 subsequently developed breast cancer. Risk discrimination was assessed using the C-statistic and calibration using the expected/observed number of incident cases across the spectrum of risk by age group (50-54, 55-59, 60-65 years) and family history of breast cancer. C-statistics were higher for BOADICEA (0.59, 95% confidence interval (CI) 0.56-0.62) and IBIS (0.57, 95% CI 0.54-0.61) than the other models (p-difference ≤ 0.04). No model except BOADICEA calibrated well across the spectrum of 15-year risk (p-value < 0.03). The performance of BOADICEA and IBIS was similar across age groups and for women with or without a family history. For middle-aged Australian women, BOADICEA and IBIS had the highest discriminatory accuracy of the six risk models, but apart from BOADICEA, no model was well-calibrated across the risk spectrum.
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ItemProspective Evaluation of the Addition of Polygenic Risk Scores to Breast Cancer Risk Models(OXFORD UNIV PRESS, 2021-06)BACKGROUND: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm and the International Breast Cancer Intervention Study breast cancer risk models are used to provide advice on screening intervals and chemoprevention. We evaluated the performance of these models, which now incorporate polygenic risk scores (PRSs), using a prospective cohort study. METHODS: We used a case-cohort design, involving women in the Melbourne Collaborative Cohort Study aged 50-75 years when surveyed in 2003-2007, of whom 408 had a first primary breast cancer diagnosed within 10 years (cases), and 2783 were from the subcohort. Ten-year risks were calculated based on lifestyle factors, family history data, and a 313-variant PRS. Discrimination was assessed using a C-statistic compared with 0.50 and calibration using the ratio of expected to observed number of cases (E/O). RESULTS: When the PRS was added to models with lifestyle factors and family history, the C-statistic (95% confidence interval [CI]) increased from 0.57 (0.54 to 0.60) to 0.62 (0.60 to 0.65) using IBIS and from 0.56 (0.53 to 0.59) to 0.62 (0.59 to 0.64) using BOADICEA. IBIS underpredicted risk (E/O = 0.62, 95% CI = 0.48 to 0.80) for women in the lowest risk category (<1.7%) and overpredicted risk (E/O = 1.40, 95% CI = 1.18 to 1.67) in the highest risk category (≥5%), using the Hosmer-Lemeshow test for calibration in quantiles of risk and a 2-sided P value less than .001. BOADICEA underpredicted risk (E/O = 0.82, 95% CI = 0.67 to 0.99) in the second highest risk category (3.4%-5%); the Hosmer-Lemeshow test and a 2-sided P value was equal to .02. CONCLUSIONS: Although the inclusion of a 313 genetic variant PRS doubles discriminatory accuracy (relative to reference 0.50), models with and without this PRS have relatively modest discrimination and might require recalibration before their clinical and wider use are promoted.
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ItemLifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies(WILEY, 2021-06-01)Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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ItemPrediagnosis alcohol intake and metachronous cancer risk in cancer survivors: A prospective cohort study(WILEY, 2021-08-15)Alcohol consumption is a known cause of cancer, but its role in the etiology of second primary (metachronous) cancer is uncertain. Associations between alcohol intake up until study enrollment (prediagnosis) and risk of metachronous cancer were estimated using 9435 participants in the Melbourne Collaborative Cohort Study who were diagnosed with their first invasive cancer after enrollment (1990-1994). Follow-up was from date of first invasive cancer until diagnosis of metachronous cancer, death or censor date (February 2018), whichever came first. Alcohol intake for 10-year periods from age 20 until decade encompassing baseline using recalled beverage-specific frequency and quantity was used to calculate baseline and lifetime intakes, and group-based intake trajectories. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. After a mean follow-up of 7 years, 1512 metachronous cancers were identified. A 10 g/d increment in prediagnosis lifetime alcohol intake (HR = 1.03, 95% CI = 1.00-1.06; Pvalue = .02) and an intake of ≥60 g/d (HR = 1.32, 95% CI = 1.01-1.73) were associated with increased metachronous cancer risk. We observed positive associations (per 10 g/d increment) for metachronous colorectal (HR = 1.07, 95% CI = 1.00-1.14), upper aero-digestive tract (UADT) (HR = 1.16, 95% CI = 1.00-1.34) and kidney cancer (HR = 1.24, 95% CI = 1.10-1.39). Although these findings were partly explained by effects of smoking, the association for kidney cancer remained unchanged when current smokers or obese individuals were excluded. Alcohol intake trajectories over the life course confirmed associations with metachronous cancer risk. Prediagnosis long-term alcohol intake, and particularly heavy drinking, may increase the risk of metachronous cancer, particularly of the colorectum, UADT and kidney.
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ItemNo Preview AvailableCumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer(W B SAUNDERS CO-ELSEVIER INC, 2020-04)BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.