Performance of the fecal immunochemical test for colorectal cancer and advanced neoplasia in individuals under age 50.

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.

Long-term Use of Hormone Replacement Therapy is Associated With a Lower Risk of Developing High-risk Serrated Polyps in Women.

GOALS/BACKGROUND: Hormone replacement therapy (HRT) and parity have been suggested protective factors against the development of colorectal polyps. However, there are a limited number of studies that have examined the relationship of these factors with high-risk adenomatous polyps (HRAP) or high-risk serrated polyps (HRSP), which may have different causes and therefore implications for screening programs. STUDY: Data from a cross-sectional study of 1384 women undergoing screening-related colonoscopy between 2008 and 2016 were analyzed. Modified Poisson regression models with robust error variance were used to determine the relative risk of developing adenomatous polyps, serrated polyps, HRAPs, and HRSPs associated with pregnancy, menopausal status, and the use of HRT (duration and type). RESULTS: Women that used HRT for ≥6 years were at a significantly lower risk of developing a HRSP [risk ratios (RR): 0.53; 95% confidence interval (CI): 0.29-0.97]. Irrespective of the duration of use, the use of HRT that included progesterone alone or with estrogen was associated with a significantly lower risk of developing a HRSP (RR: 0.54; 95% CI: 0.30-0.95). The use HRT with progesterone for ≥6 years was associated with a nonsignificant lower risk of developing a HRSP (RR: 0.42; 95% CI: 0.17-1.04). None of the reproductive factors assessed or HRT were associated with the development of adenomatous polyps or HRAPs. CONCLUSIONS: The results of this study suggests that the long-term use of HRT, and therapies that include progesterone are associated with a lower risk of developing HRSPs. These results could have implications for targeted screening for serrated polyps among women.

Examining the etiology of early-onset breast cancer in the Canadian Partnership for Tomorrow's Health (CanPath).

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/m2 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.

Estimating the future cancer management costs attributable to modifiable risk factors in Canada.

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.

RéSUMé: OBJECTIFS: Il est estimé que de 33 % à 37 % des cancers incidents au Canada sont imputables à des facteurs de risque modifiables. Des interventions ciblant ces facteurs de risque réduiraient le fardeau sanitaire et économique considérable du cancer dans la population canadienne. Nous avons estimé le futur fardeau sanitaire et économique du cancer au Canada en intégrant les données de l'étude ComPARe (Canadian Population Attributable Risk of Cancer) dans l'outil de microsimulation en ligne OncoSim. MéTHODE: À l'aide des indicateurs d'impact dans la population et du risque attribuable dans la population intégrés dans OncoSim, nous avons évalué des scénarios d'intervention mis en œuvre en 2020 axés sur les facteurs de risque, en partant de l'hypothèse que la réduction de la prévalence des facteurs de risque ciblés serait atteinte d'ici 2032 avec une période de latence de 12 ans. RéSULTATS: Nous estimons que le tabagisme sera le facteur qui contribuera le plus aux coûts du cancer, avec un coût de 44,4 milliards $ CA entre 2032 et 2044. Il est estimé qu'une part de 3,3 milliards $ CA de ce coût pourrait être évitée en réduisant de 30 % la prévalence du tabagisme d'ici 2022. Après le tabagisme, les coûts de prise en charge du cancer les plus élevés sont associés à l'inactivité physique et au surpoids, qui représentent respectivement 10,7 milliard $ CA (dont 2,7 milliards $ évitables) et 9,8 milliards $ CA (dont 3,2 milliards $ évitables). Les coûts évitables pour d'autres facteurs de risque vont de 90 millions $ CA à 2,5 milliards $ CA. CONCLUSION: Des interventions ciblant les facteurs de risque de cancer modifiables pourraient prévenir un nombre considérable de cas de cancers incidents et épargner des milliards de dollars en coûts de prise en charge du cancer. Avec les budgets serrés et la hausse des coûts des soins du cancer au Canada, ces modèles de simulation et leurs résultats permettent aux chercheurs et aux responsables des politiques d'éclairer les décisions et de hiérarchiser et d'évaluer les programmes d'intervention.

Estimates of future cancer mortality attributable to modifiable risk factors in Canada.

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.

RéSUMé: OBJECTIFS: Les facteurs de risque modifiables associés au cancer (liés au mode de vie, à l'environnement, aux maladies infectieuses) ont des effets à la fois sur l'incidence du cancer et sur la mortalité par cancer à l'échelle de la population. La plupart des études qui estiment ce fardeau portent sur l'incidence du cancer. Cependant, comme les facteurs de risque susmentionnés sont associés à des cancers dont les taux de mortalité sont disparates, le fardeau associé à l'incidence du cancer pourrait différer de la mortalité par cancer. En conséquence, l'estimation de la mortalité par cancer imputable à ces facteurs de risque pourrait éclairer la prévention du cancer. Nous estimons ici les décès futurs par cancer et le nombre de décès évitables au Canada dus à des facteurs de risque modifiables. MéTHODE: Les données projetées sur la mortalité par cancer proviennent d'OncoSim, un outil de microsimulation en ligne. Elles ont été appliquées au cadre méthodologique que nous avions déjà utilisé pour estimer les risques attribuables dans la population et les fractions de l'incidence potentielle des facteurs de risque modifiables sur l'incidence canadienne du cancer. RéSULTATS: Selon nos estimations, entre 2024 et 2047, la plupart des décès par cancer seront imputés au tabagisme, qui causera en moyenne 27 900 décès par année. Si les tendances actuelles au Canada en matière de surpoids se maintiennent, les décès par cancer attribuables au surpoids doubleraient, passant de 2 786 décès en 2024 à 5 604 en 2047, et le surpoids deviendrait la deuxième cause modifiable de décès par cancer. En appliquant des cibles de réduction de ces facteurs de risque, jusqu'à 34 600 décès par cancer pourraient être évités entre 2024 et 2047. CONCLUSION: Les résultats de notre simulation confirment nos constatations antérieures sur le fardeau de l'incidence du cancer, car la diminution du fardeau global du cancer sera accélérée par une combinaison de la diminution de l'incidence du cancer et de l'amélioration des résultats de survie grâce à l'amélioration des traitements.

Combinations of modifiable lifestyle behaviours in relation to colorectal cancer risk in Alberta's Tomorrow Project.

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.

Cohort profile: The Forzani & MacPhail Colon Cancer Screening Centre biorepository, Calgary, Alberta.

PURPOSE: The 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. PARTICIPANTS: Currently, 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 DATE: The 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 PLANS: The 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.

Association Between Endoscopist Annual Procedure Volume and Colonoscopy Quality: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC. METHODS: We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes. RESULTS: We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98-1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08-1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90-1.00). There was considerable heterogeneity among most analyses. CONCLUSIONS: In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.

Vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

There is suggestive evidence for the role of vitamin D in the development of colorectal cancer (CRC). Due to high latitudes in Canada, many Canadians are vitamin D deficient throughout winter. In this analysis, we examined the association between vitamin D supplement use and high-risk adenomatous polyps (HRAPs). The study population was drawn from the biorepository at the Forzani & MacPhail Colon Cancer Screening Centre (CCSC) in Calgary. Individuals enrolled between 2013 and 2016 between the age of 50 and 74 years (n = 1409) were included. When examining the association between any supplemental vitamin D use and HRAPs, a protective effect is observed with an ORadj of 0.57 (95% CI: 0.33-0.96). Similarly, meeting the recommended daily intake (RDI) of vitamin D (600 IU) is protective against HRAPs with an ORadj of 0.78 (95% CI: 0.62-0.99). This study suggests that adequate vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

Mutational landscape differences between young-onset and older-onset breast cancer patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Estimates of the current and future burden of cancer attributable to lack of physical activity in Canada.

Physical activity reduces the risk of many cancers, yet the prevalence of inadequate physical activity among Canadians remains high. Here we estimated the current attributable and future avoidable burden of cancer related to inadequate physical activity among Canadian adults. Population attributable risk (PAR) for all cancers associated with inadequate physical activity were estimated using relative risks obtained from comprehensive reports, meta-analyses and pooled analyses. Cancer incidence data were acquired from the Canadian Cancer Registry. Physical activity data were taken from Canadian Community Health Survey (Cycle 2.1, 2003), in which respondents were classified as "physically inactive" (<1.5 kcal/kg/day), "moderately active" (1.5-2.9 kcal/kg/day) or "physically active (≥3.0 kcal/kg/day). We defined "inadequate physical activity" as being either "physically inactive" or "moderately active" to determine the PAR of cancer due to inadequate physical activity. We estimated the future burden of inadequate physical activity using potential impact fractions and a series of intervention scenarios, including 10% to 50% reductions in inadequate physical activity from 2015 to 2042. For 2015, the total attributable burden due to inadequate physical activity for associated cancers was 10.6% and 4.9% for all cancers. A 50% reduction in inadequate physical activity could avoid 39,877 cumulative cases of cancer by 2042. Over 9000 cancer cases in 2015 were estimated to be attributable to inadequate physical activity and 5170 incident cases of cancer could be prevented with increases in physical activity levels by 2042. Policies aimed at increasing physical activity among Canadian could have a meaningful impact for cancer prevention.

Estimates of the current and future burden of cancer attributable to sedentary behavior in Canada.

Leisure-time sedentary behavior is an emerging modifiable risk factor for cancer. We estimated the proportion of cancers attributed to leisure-time sedentary behavior as a separate risk factor from physical activity in Canada for 2015. We projected numbers of future avoidable cancers by 2042 using various assumed levels of reduced leisure-time sedentary behavior in the population. We calculated population attributable risks (PAR) for associated cancers and all-cancers associated with leisure-time sedentary behavior. Our analysis used pooled data on leisure-time sedentary behavior from the Canadian Community Health Survey (CCHS), and incident cancer data from the Canadian Cancer Registry (CCR). Survey respondents were categorized into three levels of leisure-time sedentary behavior, "<3 h/day", "≥3-<6 h/day", and "≥6 h/day". Estimates for the future burden of leisure-time sedentary behavior were calculated using the potential impact fractions framework (PIF) and counterfactual scenarios, from 10% to 50% decreases in leisure-time sedentary behavior. The estimated prevalence of leisure-time sedentary behavior at the highest level (≥6 h/day) in Canada during the 2000s was 9.9% among both sexes combined across age-groups. The total attributable burden due to leisure-time sedentary behavior was estimated to be 10.3% for associated cancers and 6.5% for all-cancers in 2015. A 50% reduction in leisure-time sedentary behavior across the Canadian population could avoid 4054 cancers by 2042. We estimated that over 3000 cancer cases in Canada were attributable to leisure-time sedentary behavior in 2015, and that that 4054 incident cancer cases could be prevented by 2042 with meaningful reductions in leisure-time sedentary behavior.

Central body fatness is a stronger predictor of cancer risk than overall body size.

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-2) 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.

Neonatal, 1-59 month, and under-5 mortality in 597 Indian districts, 2001 to 2012: estimates from national demographic and mortality surveys.

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.