The importance of body size versus weight distribution for cancer risk is unclear. We investigated associations between measures of body size and shape and the risk of developing cancer. The study ...population consisted of 26,607 participants from the Alberta's Tomorrow Project cohort. Two main measures of body shape and size were examined: i) body mass index (BMI) and ii) waist circumference (WC). Incident cancers were identified via linkage to the Alberta Cancer Registry. Cox proportional hazards models were used. Males and females classified as obese (BMI ≥ 30 kg /m
) have a 33% and 22% increased risk of all-cancer, respectively, than their normal weight counterparts. Similar all-cancer risk increases are observed for those above sex-specific WC guidelines. Mutual adjustment for WC attenuates the association between BMI and all-cancer risk, especially among females. Central adiposity appears to be a stronger predictor of all-cancer risk than body size.
The objective of this study was to identify distinct clusters of individuals that exhibit unique patterns of modifiable lifestyle-related behaviours and to determine how these patterns are associated ...with the risk of developing colorectal cancer (CRC). The study consisted of 26,460 participants and 267 CRC cases from Alberta's Tomorrow Project. Exploratory latent class analysis of risk behaviours (obesity, physical inactivity, meat consumption, smoking, alcohol consumption, and fruit and vegetable consumption) and Cox proportional hazard models were utilized. Seven unique behavioural groups were identified, where the risk of CRC was 2.34 to 2.87 times greater for high risk groups compared to the low risk group. Sex-specific models identified higher risk groups among men (Hazard Ratios HRs: 3.15 to 3.89) than among women (HRs: 1.99 to 2.19). Targeting groups defined by clustering of behaviours could potentially lead to more effective prevention of CRC on a population level.
Purpose
Breast cancer incidence among younger women (under age 50) has increased over the past 25 years, yet little is known about the etiology among this age group. The objective of this study was ...to investigate relationships between modifiable and non-modifiable risk factors and early-onset breast cancer among three prospective Canadian cohorts.
Methods
A matched case–control study was conducted using data from Alberta’s Tomorrow Project, BC Generations Project, and the Ontario Health Study. Participants diagnosed with breast cancer before age 50 were identified through provincial registries and matched to three control participants of similar age and follow-up. Conditional logistic regression was used to examine the association between factors and risk of early-onset breast cancer.
Results
In total, 609 cases and 1,827 controls were included. A body mass index ≥ 30 kg/m
2
was associated with a lower risk of early-onset breast cancer (OR 0.65; 95% CI 0.47–0.90), while a waist circumference ≥ 88 cm was associated with an increased risk (OR 1.58; 95% CI 1.18–2.11). A reduced risk was found for women with ≥ 2 pregnancies (OR 0.76; 95% CI 0.59–0.99) and a first-degree family history of breast cancer was associated with an increased risk (OR 1.95; 95% CI 1.47–2.57).
Conclusions
In this study, measures of adiposity, pregnancy history, and familial history of breast cancer are important risk factors for early-onset breast cancer. Evidence was insufficient to conclude if smoking, alcohol intake, fruit and vegetable consumption, and physical activity are meaningful risk factors. The results of this study could inform targeted primary and secondary prevention for early-onset breast cancer.
The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 ...mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours.
In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages "deconstructSigs" and "SomaticSignatures" to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset.
Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young-onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young-onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. Signatures resembling COSMIC signatures 2 and 13 were observed among both age groups. We identified a class of tumours with a unique combination of signatures that may be associated with young age of onset.
The results of this exploratory study provide some evidence that the mutational landscape and mutational signatures among young-onset breast cancer are different from those of older-onset patients. The characterization of young-onset tumours could provide clues to their etiology which may inform future prevention. Further studies are required to confirm our findings.
Objectives
Modifiable lifestyle, environmental, and infectious risk factors associated with cancer impact both cancer incidence and mortality at the population level. Most studies estimating this ...burden focus on cancer incidence. However, because these risk factors are associated with cancers of disparate mortality rates, the burden associated with cancer incidence could differ from cancer mortality. Therefore, estimating the cancer mortality attributable to these risk factors provides additional insight into cancer prevention. Here, we estimated future cancer deaths and the number of avoidable deaths in Canada due to modifiable risk factors.
Methods
The projected cancer mortality data came from OncoSim, a web-based microsimulation tool. These data were applied to the methodological framework that we previously used to estimate the population attributable risks and the potential impact fractions of modifiable risk factors on Canadian cancer incidence.
Results
We estimated that most cancer deaths will be attributed to tobacco smoking with an average of 27,900 deaths annually from 2024 to 2047. If Canada’s current trends in excess body weight continue, cancer deaths attributable to excess body weight would double from 2786 deaths in 2024 to 5604 deaths in 2047, becoming the second leading modifiable cause of cancer death. Applying targets to reduce these risk factors, up to 34,600 cancer deaths could be prevented from 2024 to 2047.
Conclusion
Our simulated results complement our previous findings on the cancer incidence burden since decreasing the overall burden of cancer will be accelerated through a combination of decreasing cancer incidence and improving survival outcomes through improved treatments.
Objectives
An estimated 33–37% of incident cancers in Canada are attributable to modifiable risk factors. Interventions targeting these risk factors would minimize the substantial health and economic ...burdens Canadians face due to cancer. We estimate the future health and economic burden of cancer in Canada by incorporating data from the Canadian Population Attributable Risk of Cancer (ComPARe) study into OncoSim, a web-based microsimulation tool.
Methods
Using the integrated OncoSim population attributable risk and population impact measures, we evaluated risk factor-targeted intervention scenarios implemented in 2020, assuming the targeted risk factor prevalence reduction would be achieved by 2032 with a 12-year latency period.
Results
We estimate that smoking will be the largest contributor to cancer-related costs, with a cost of CAD $44.4 billion between 2032 and 2044. An estimated CAD $3.3 billion of the cost could be avoided with a 30% reduction in smoking prevalence by 2022. Following smoking, the next highest cancer management costs are associated with inadequate physical activity and excess body weight, accounting for CAD $10.7 billion ($2.7 billion avoidable) and CAD $9.8 billion ($3.2 billion avoidable), respectively. Avoidable costs for other risk factors range from CAD $90 million to CAD $2.5 billion.
Conclusion
Interventions targeting modifiable cancer risk factors could prevent a substantial number of incident cancer cases and billions of dollars in cancer management costs. With limited budgets and rising costs in cancer care in Canada, these simulation models and results are valuable for researchers and policymakers to inform decisions and prioritize and evaluate intervention programs.
Summary Background India has the largest number of child deaths of any country in the world, and has wide local variation in under-5 mortality. Worldwide achievement of the UN 2015 Millennium ...Development Goal for under-5 mortality (MDG 4) will depend on progress in the subregions of India. We aimed to estimate neonatal, 1–59 months, and overall under-5 mortality by sex for 597 Indian districts and to assess whether India is on track to achieve MDG 4. Methods We divided the 2012 UN sex-specific birth and mortality totals for India into state totals using relative birth rates and mortality from recent demographic surveys of 24 million people, and divided state totals into totals for the 597 districts using 3 million birth histories. We then split the results into neonatal mortality and 1–59 month mortality using data for 109 000 deaths in children younger than 5 years from six national surveys. We compared results with the 2001 census for each district. Findings Under-5 mortality fell at a mean rate of 3·7% (IQR 3·2–4·9) per year between 2001 and 2012. 222 (37%) of 597 districts are on track to achieve the MDG 4 of 38 deaths in children younger than 5 years per 1000 livebirths by 2015, but an equal number (222 37%) will achieve MDG 4 only after 2020. These 222 lagging districts are home to 41% of India's livebirths and 56% of all deaths in children younger than 5 years. More districts lag behind the relevant goal for neonatal mortality (251 42%) than for 1–59 month mortality (197 33%). Just 81 (14%) districts account for 37% of deaths in children younger than 5 years nationally. Female mortality at ages 1–59 months exceeded male mortality by 25% in 303 districts in nearly all states of India, totalling about 74 000 excess deaths in girls. Interpretation At current rates of progress, MDG 4 will be met by India around 2020—by the richer states around 2015 and by the poorer states around 2023. Accelerated progress to reduce mortality during the neonatal period and at ages 1–59 months is needed in most Indian districts. Funding Disease Control Priorities 3, Canadian Institutes of Health Research, International Development Research Centre, US National Institutes of Health.
PurposeThe Colon Cancer Screening Centre (CCSC) biorepository (Calgary, Canada) supports a wide range of research topics related to colorectal cancer (CRC) by collecting, and storing biospecimens ...(blood, urine, normal colon tissue) from consenting patient participants. Housing unique biospecimens along with detailed participant lifestyle and health history questionnaire data, the CCSC biorepository can support a variety of research related to CRC risk factors, biomarkers, genetic causes and more.ParticipantsCurrently, 2292 average risk CRC patients have consented to participate in the CCSC cohort and have provided stored biospecimens. The collected samples and data provide important high-quality materials for research, discovery and evaluation related to CRC screening and carcinogenesis and is available for access by outside researchers. In addition to biological samples, the CCSC collects detailed patient information on their lifestyle, physical activity and dietary patterns through questionnaires at the time of their enrolment.Findings to dateThe majority of participants (75%) are between 50 and 64 years of age. Women make up 46% (1055) of the cohort. Additional characteristics of the cohort included 44% reporting a body mass index of 25–30 kg/m2 (overweight), 53% having never smoked tobacco and 13% having a family member with CRC.Future plansThe CCSC cohort plans to include the recruitment of high risk CRC cohorts. High-risk participants would comprise patients with a positive faecal immunochemical test and family history of CRC.
•Colorectal cancer (CRC) incidence is increasing among those younger than screening eligibility (<50 years).•Screening programs have expanded eligibility but test performance in these other groups is ...unclear.•FIT performance may be lower for younger populations compared to average risk.•Evidence is limited with high heterogeneity in the included studies.•More information is needed about whether FIT is a useful and effective screening tool for younger populations.
The increased demand for colonoscopy combined with increased incidence of colorectal cancer (CRC) among younger populations presents a need to determine FIT performance among individuals in this age group. We conducted a systematic review to assess test performance characteristics of FIT in detecting CRC and advanced neoplasia in younger age populations. A search through December 2022 identified published articles assessing the sensitivity and specificity of FIT for advanced neoplasia or CRC among populations under age 50. Following the search, 3 studies were included in the systematic review. Sensitivity to detect advanced neoplasia ranged from 0.19 to 0.36 and specificity between 0.94 and 0.97 and the overall sensitivity and specificity were 0.23 (0.17–0.30) and 0.96 (0.94–0.98), respectively. Two studies that assessed these metrics in multiple age categories found similar sensitivity and specificity across all age groups 30–49. Sensitivity and specificity to detect CRC was assessed in one study and found no significant differences by age groups. These results suggest that FIT performance may be lower for younger individuals compared to those typically screened for CRC. However, there were few studies available for analysis. Given increasing recommendations to expand screening in younger age groups, more research is needed to determine whether FIT is an adequate screening tool in this population.
•Four RCTs of CRC screening sigmoidoscopy were reviewed.•The OncoSim model was able to simulate the results of the four RCTs.•Predicted reductions in CRC incidence and mortality agreed with ...observations.•These results validate OncoSim CRC natural history and screening assumptions.
Projection of the effect of cancer screening interventions are frequently conducted using complex simulation models. It is important that such models demonstrate their ability to replicate observational results on the effect of screening. We present results using the OncoSim-CRC microsimulation model to replicate results from four randomized trials (RCTs) of sigmoidoscopy screening for colorectal cancer (CRC).
The published results of four RCTs of sigmoidoscopy were reviewed. Two key outcomes were identified: the intention-to-treat hazard ratios (HR) for CRC incidence and CRC mortality for the screening versus control arms. Each RCT study arm was simulated within OncoSim-CRC using the study specific entry criteria, follow-up and observed participation and compliance rates. The ratio of predicted cases (deaths) between intervention arm and control arm was used to estimate the HRs.
The RCTs differed in the implementation of sigmoidoscopy screening and only one (PLCO) used more than one cycle. All four RCTs found significant reductions, HR <1, in CRC incidence (range 0.77–0.82) and three for CRC mortality (range 0.69–0.78). The four study cohorts were successfully simulated to match the age and sex structure and length of follow-up of the study cohorts. Each OncoSim-CRC trial-specific predicted reduction fell within the confidence intervals for the observed HR for CRC incidence and CRC mortality for the corresponding trial. The predicted ranges of HRs for incidence was 0.74–0.82 and for mortality was 0.66–0.76 for the four trials.
OncoSim-CRC predicted reductions in CRC incidence and mortality agreed well with observed in RCTs of sigmoidoscopy screening.
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