Abstract
Background
Although adolescent and young adult (AYA) cancers represent a unique spectrum of malignancies, epidemiological studies of cancer incidence often group AYAs together with younger ...or older populations, obscuring patterns specific to this population.
Methods
We examined AYA cancer incidence trends in 41 countries over a 15-year period using the CI5plus database. Truncated age-standardized incidence rates were calculated and the annual percentage change was assessed, with statistical significance corresponding to a 95% confidence interval that does not include zero.
Results
From 1998 to 2012, the 41 included countries contributed a total of 1 846 588 cancer cases and 3.1 billion person-years among AYAs. Although statistically significant increases in the overall cancer burden were observed in 23 countries, the magnitude varied considerably, with the greatest increase in incidence observed in South Korea (annual percentage change2002–2012 = 8.5%, 95% confidence interval = 7.6% to 9.4%) due to thyroid cancer. Notable trends included sharp increases in the incidence of obesity-related malignancies among AYAs; indeed, statistically significant increases were observed among AYAs for 10 of 11 and 9 of 11 obesity-related cancer sites in the US and UK, respectively, with at least five obesity-related cancers statistically significantly increasing in Canada, Japan, South Korea, Australia, and the Netherlands. Other striking trends were noted for thyroid and testicular cancer, with statistically significantly increasing rates observed in 33 and 22 countries, respectively, whereas statistically significant declines in incidence were observed for smoking-related cancers, cervical cancer, and Kaposi sarcoma in many countries.
Conclusions
Our results highlight the future health-care needs related to treatment as well as the urgency for public health initiatives that can mitigate the increasing burden of cancer in AYAs.
The incidence of early-onset colorectal cancer (eoCRC) has been increasing in North America. Debate remains as to whether the trends by topography, histology, stage, or mortality in this population ...are amenable to intervention from screening.
CRC incidence (2000-2017) and mortality (2000-2018) data were obtained from the Canadian Cancer Registry and Vital Statistics. Annual percentage changes (APC) in the incidence (topography and histology) and mortality of eoCRC were estimated using joinpoint regression. Incidence of late-stage CRC (III or IV) versus early-stage CRC (I or II) was compared between the eoCRC (age 20-49 years) and eligible screening (age 50-74 years) groups with Poisson regression.
Among women aged 20-49 years, the incidence of CRC significantly increased from 2000 to 2017 in both the distal colon (APC = 1.40) and rectum (APC = 3.00), whereas for men aged 20-49 years, the CRC incidence increased in the proximal colon (APC = 1.10), distal colon (APC = 3.00), and rectum (APC = 3.70). Among both men and women aged 20-49 years, the incidence of nonmucinous adenocarcinomas significantly increased (APC: 1.90 and 2.30, respectively), whereas mucinous adenocarcinomas decreased for women (APC = -1.60) and remained stable for men. Adults aged 30 to 49 years, when diagnosed with CRC, had a significantly higher risk of being diagnosed with a late-stage CRC compared with those in the age group of 50-74 years. Rectal cancer mortality increased from 2000 to 2018 in the eoCRC group (APC for women and men 3.80 and 3.40, respectively).
Emerging data support future modifications to guidelines on screening for eoCRC in Canada. Further research is required on the effect, cost-effectiveness, and risk prediction for targeted screening within this group.
Nearly one in two Canadians are expected to be diagnosed with cancer in their lifetime. However, there are opportunities to reduce the impact of modifiable cancer risk factors through well-informed ...interventions and policies. Since no comprehensive Canadian estimates have been available previously, we estimated the proportion of cancer diagnosed in 2015 and the future burden in 2042 attributable to lifestyle and environmental factors, and infections. Population-based historical estimates of exposure prevalence and their associated risks for each exposure-cancer site pair were obtained to estimate population attributable risks, assuming the exposures were distributed independently and that the risk estimates were multiplicative. We estimated that between 33 and 37% (up to 70,000 cases) of incident cancer cases among adults aged 30 years and over in 2015 were attributable to preventable risk factors. Similar proportions of cancer cases in males (34%) and females (33%) were attributable to these risk factors. Tobacco smoking and a lack of physical activity were associated with the highest proportions of cancer cases. Cancers with the highest number of preventable cases were lung (20,100), colorectal (9800) and female breast (5300) cancer. If current trends in the prevalence of preventable risk factors continue into the future, we project that by 2042 approximately 102,000 incident cancer cases are expected to be attributable to these risk factors per year, which would account for roughly one-third of all incident cancers. Through various risk reduction interventions, policies and public health campaigns, an estimated 10,600 to 39,700 cancer cases per year could be prevented by 2042.
•Many lifestyle behaviours, environmental exposures and infections are preventable risk factors for cancer.•We estimated the impacts of these risk factors on the current burden of cancer in Canada.•An estimated 33% of cancer cases diagnosed in 2015 were attributable to preventable risk factors.•Tobacco smoking, a lack of physical activity, and excess weight were the leading preventable causes of cancer in 2015.•Up to 40,000 cancers per year in Canada could be prevented by 2042 by reducing exposure to modifiable cancer risk factors.
In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to ...estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.
Western populations are losing the battle over healthy weight management, and excess body weight is a notable cancer risk factor at the population level. There is ongoing interest in pharmacological ...interventions aimed at promoting weight loss, including GLP-1 receptor agonists (GLP-1RA), which may be a useful tool to stem the rising tide of obesity-related cancers.
To investigate the potential of next generation weight loss drugs (NGWLD) like GLP-1RA in population-level chemoprevention.
We used the OncoSim microsimulation tool to estimate the population-level reductions in obesity and the potentially avoidable obesity-related cancers in Canada over the next 25 years.
We estimated a total of 71 281 preventable cancers by 2049, with 36 235 and 35 046 cancers prevented for females and males, respectively. Among the 327 254 total projected cancer cases in 2049, 1.3% are estimated to be preventable through intervention with NGWLD.
Pharmacologic intervention is not the ideal solution for the obesity-related cancer crisis. However, these agents and subsequent generations provide an additional tool to rapidly reduce body weight and adiposity in populations that have been extremely challenging to reduce weight with standard diet and exercise approaches. Additional research is needed around approaches to prevent initial weight gain and maintain long-term weight loss.
Neuroblastoma (NB) is one of the most common childhood malignancies. Currently, high risk NB carries a poor outcome and significant treatment related toxicities and, thus has been a focus for new ...therapeutics research in pediatric oncology. In this study, we evaluated the effects of the MEK inhibitor cobimetinib, as a single agent and in combinations, on the growth, survival and differentiation properties against a molecularly representative panel of NB cell lines.
In vitro anti-proliferative activity of cobimetinib alone or in combination was investigated by cell viability assays and its target modulatory activity was evaluated using phospho-kinases antibody arrays and western blot analysis. To determine the effect of combination with cis-RA on differentiation and resulting enhanced cellular cytotoxicity, the expression of glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) expression levels were examined by immuno-fluorescence.
Our findings show that cobimetinib alone induced a concentration-dependent loss of cell viability in all NB cell lines. In addition, cobimetinib showed feedback activation of MEK1/2, and the dephosphorylation of extracellular signal-regulated kinases (ERK1/2) and c-RAF, providing information on the biological correlates of MEK inhibition in NB. Combined treatment with cis-RA, led to differentiation and enhanced sensitization of NB cells lines to cobimetinib.
Collectively, our results provide evidence that cobimetinib, in combination with cis-RA, represents a feasible option to develop novel treatment strategies for refractory NB.
Although previous studies have examined the burden of cancer attributable to tobacco smoking, updated estimates are needed given the dramatic changes in smoking behaviours over the last 20 years. In ...this study, we estimate the proportion of cancer cases in 2015 attributable to past tobacco smoking and passive exposure in Canada and the proportion of cancers in the future that could be prevented through the implementation of interventions targeted at reducing tobacco use. Data from the Canadian Community Health Survey (2003) were used to estimate the prevalence of active tobacco smoking and passive exposure. Population attributable risk estimates were employed to estimate the proportion of cancers attributable to tobacco in 2015. The prevalence of active tobacco smoking and passive exposure was projected to 2032 and cancer incidence was projected from 2016 to 2042 to estimate the future burden of cancer attributable to tobacco. In 2003, 30% and 24% of Canadians were former and current smoker, respectively and 24% had been exposed to tobacco smoke in the past. We estimated that 17.5% (32,655 cases; 95% CI: 31,253–34,034) of cancers were attributable to active tobacco smoking and 0.8% (1408 cases; 95% CI: 1048–1781) to passive tobacco exposure in never smokers. Between 41,191 and 50,696 cases of cancer could be prevented by 2042 under various prevention scenarios. By decreasing passive tobacco exposure by 10–50%, between 730 and 3650 cancer cases could be prevented by 2042. Strategies focused on reducing the prevalence of tobacco smoking are crucial for cancer control in Canada.
•17.5% of cancers diagnosed in Canada in 2015 were attributable to tobacco smoking.•0.8% of cancers diagnosed in Canada in 2015 were attributable to passive tobacco smoke exposure.•Over 70% of lung cancer was attributable to tobacco smoking.•Over 50,000 cases of cancer could be prevented by 2042 by reducing the prevalence of tobacco smoking by 50%.
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.
•Prostate, breast, lung and colorectal cancer account for over 50% diagnosed in Canada.•Generally, incidence rates in Canada are expected to increase over the next 30 years.•Cancer incidence is ...projected to increase 83% from 96,460 in 2012 to 176,704 in 2042.
Cancer is the leading cause of death in Canada and the estimated annual spending associated with cancer is approximately $7.5 billion. Projecting the future burden of cancer in Canada is essential for health planning and evaluation. We aimed to estimate the future incidence of cancer in Canada to 2042.
Age-sex-region-specific cancer incidence data were obtained for the years 1983-2012 and cancer incidence was projected from 2013 to 2042 for the top five cancer sites. The modelling algorithm combined a mixture of cancer projection methods to select the best-fitted model. When the chosen model produced by the modelling algorithm resulted in estimates that were not consistent with expert opinion, an alternate model was selected that took into consideration historical changes in policy, screening and lifestyle behaviours. Incidence projections were made for Canada and its provinces.
Lung cancer incidence is estimated to rise to 14,866 cases in men and 19,162 in women in 2042. Colorectal cancer incidence is estimated to rise to 28,146 in men and 21,102 in women. Cases of bladder cancer are projected to rise to 10,708 and 3,364 in men and women, respectively. Breast cancer incidence is predicted to rise to 40,712 and prostate cancer incidence is projected to rise to 92,949.
These cancer incidence projections up to 2042 can be used for planning cancer control strategies and prevention programs. Given the ongoing changes in the prevalence of risk factors and in cancer prevention policies, these estimates should be interpreted with caution.
PDF
