Craniofacial Microsomia, Associated Congenital Anomalies, and Risk Factors in 63 Cases from the Alberta Congenital Anomalies Surveillance System.

OBJECTIVE: To report associated congenital anomalies with unexplained craniofacial microsomia (CFM) and the phenotypic overlap with other recurrent constellations of embryonic malformations (RCEM), and to assess prenatal and perinatal risk factors. STUDY DESIGN: This is a retrospective cross-sectional study. Cases with CFM, delivered between January 1, 1997, and December 31, 2019, were abstracted from the population-based Alberta Congenital Anomalies Surveillance System. Livebirths, stillbirths, and early fetal losses were reviewed to include all types of pregnancy outcomes along the spectrum of this condition. Prenatal and perinatal risk factors were compared with the Alberta birth population to assess differences between the 2 groups. RESULTS: There were 63 cases with CFM, yielding a frequency of 1 per 16 949. There was a high rate of cases (65%) with anomalies outside the craniofacial and vertebral regions. Congenital heart defects were the most common (33.3%). A single umbilical artery was found in 12.7% of cases. The twin/triplet rate of 12.7% was significantly higher than the Alberta rate of 3.3% (P < .0001). There was an overlap with a second RCEM condition in 9.5% of cases. CONCLUSIONS: Although CFM is primarily a craniofacial condition, the majority of cases have congenital anomalies affecting other systems requiring additional assessments, including an echocardiogram, renal ultrasound examination, and a complete vertebral radiograph. The high rate of an associated single umbilical artery raises the possibility of a related etiological mechanism. Our findings support the proposed concept of RCEM conditions.

Prevalence rates study of selected isolated non-Mendelian congenital anomalies in the Hutterite population of Alberta, 1980-2016.

A study of the prevalence rates for selected isolated non-Mendelian congenital anomalies in the Hutterite Brethren of Alberta, Canada was undertaken to further examine longitudinal data in this isolated community that was last reported in 1985 (Lowry et al., 1985), although there are numerous publications on recessive disorders (Boycott et al., 2008; Triggs-Raine et al., 2016). Cases were ascertained from the Alberta Congenital Anomaly Surveillance System for the years 1997-2016. Since our initial results showed some surprising findings in the Hutterite Brethren, such as zero cases of spina bifida, cleft lip and palate, gastroschisis, and omphalocele, and a significant excess of cases with hypospadias, we extended the study to prior years (1980-1996) for selected anomalies. For the extended study period (1980-2016), there was a significant increased prevalence of hypospadias, tetralogy of Fallot and tricuspid atresia in the Hutterite population, and although not statistically significant, zero cases of cleft lip with cleft palate, gastroschisis and omphalocele were confirmed. Further research is needed to determine the precise effects of rural environmental exposures, lifestyle factors, and genetic associations for selected multifactorial congenital anomalies.

Estimates of the current and future burden of cancer attributable to alcohol consumption in Canada.

Alcohol consumption is associated with elevated risk of oropharyngeal, laryngeal, esophageal, colon, rectal, breast, liver, pancreatic and stomach cancers. The purpose of this analysis was to provide national and provincial estimates of the number and proportion of cancers attributable to alcohol consumption in Canada and to project the numbers of potentially avoidable cancers using possible intervention scenarios. We estimated the population attributable risk (PAR) for cancers associated with alcohol consumption levels (drinks/day) using: i) relative risks obtained from the World Cancer Research Fund/(WCRF) reports or meta-analyses, ii) alcohol consumption (prevalence) data from the 2003 Canadian Community Health Survey, and iii) cancer incidence data from the 2015 Canadian Cancer Registry. We used potential impact fractions (PIFs) to estimate the future avoidable cancer burden under four counterfactual scenarios: (1) lowering alcohol consumption to meet the WCRF low risk guidelines, (2) meeting the Canada's Low-Risk Drinking Guidelines, (3) reducing daily intake by one drink/day, and (4) decreasing consumption to 50% of the 2003 levels by 2032. We estimated that 3282 incident cancer cases (5.2% of alcohol-associated cancers and 1.8% of all cancers) diagnosed in Canada in 2015 were attributable to alcohol consumption. At the current consumption levels, alcohol-attributable cancers are expected to increase to 10,122 (8.8% of cases among alcohol-associated cancers) by 2042. Under the best case scenario, reducing alcohol consumption to 50% of 2003 levels by 2032, could prevent 70,261 cases by 2042. Strategies that effectively reduce alcohol consumption at a population level can have a meaningful impact on reducing the cancer burden in Canada.

Estimates of the current and future burden of cancer attributable to active and passive tobacco smoking in Canada.

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.

Estimates of the current and future burden of cancer attributable to low fruit and vegetable consumption in Canada.

Low fruit and vegetable consumption is associated with colorectal cancer and may be associated with lung, breast, bladder, pancreatic, ovarian, liver, stomach, esophageal, head and neck cancers. We estimated the current attributable and future avoidable burden of cancer associated with low fruit and vegetable consumption in Canada. Using data on cancer incidence, exposure prevalence and risk effects, we estimated the population attributable risk (PAR) for cancers associated with low fruit and vegetable consumption as well as the future avoidable burden. The prevalence of fruit and vegetable consumption was projected to 2032 and cancer incidence was projected to 2042 to estimate the future potential impact fraction of cancer attributable to low fruit and vegetable consumption. Based on estimates from the Canadian Community Health Survey, the prevalence of low fruit (<4 servings/day) and vegetable (<4 servings/day) consumption in the Canadian population was 80.5% and 86.6%, respectively. The PARs for colorectal cancer associated with low fruit and vegetable consumption were 6.1% (1, 371 cases) and 2.2% (487 cases), respectively. For all incident cancers in 2015, 0.7% and 0.3% were attributable to low fruit and vegetable consumption, respectively. An increase of one serving/week of fruit could prevent 20,710 colorectal cancer cases cumulatively by 2042, and the same increase in vegetable consumption could prevent 10,185 cases. Although more research on the association between fruit and vegetable consumption and cancer risk is needed, our results demonstrate that with reasonable increases in current fruit and vegetable consumption by Canadians, over 30,000 colorectal cancer cases could be prevented by 2042.

Estimates of the current and future burden of cancer attributable to red and processed meat consumption in Canada.

Red meat and processed meat have been consistently associated with an increased risk of colorectal, stomach, pancreatic cancer and esophageal cancer (processed meat only). The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to red and processed meat consumption in Canada. We estimated the population attributable risk of cancer separately for red meat consumption (beef, lamb, and pork, excluding processed meat) and processed meat consumption (sausage and bacon) incorporating current cancer incidence data, relative risks, and exposure prevalence. We also estimated the future avoidable burden of cancer from 2015 to 2042 for Canada and by province using the potential impact fraction associated with various potential intervention scenarios intended to reduce consumption, ranging from a decrease of 0.2 servings/week to 2.0 servings/week among the adult Canadian population aged 20 and over. The estimated mean red meat consumption in the Canadian population in 2007 to 2011 was approximately 3.2 times per week. In addition, Canadians consume an average of 1.2 times of processed meat per week. In 2015, an estimated 5.9% of associated cancers and 0.9% of all cancers were attributable to red meat consumption. An estimated 4.5% of associated cancers and 0.7% of all cancers were attributable to processed meat consumption. A mean decrease of 0.5 servings/week of red meat or processed meat could prevent about 8700 or 16,600 cancer cases, respectively, between 2015 and 2042. In conclusion, a small but meaningful cancer burden is associated with red and processed meat consumption. Interventions aimed at reducing consumption at the population level have the potential in the prevention of many cancers in Canada.

Estimates of the current and future burden of cancer attributable to excess body weight and abdominal adiposity in Canada.

The increasing prevalence of obesity among Canadians has important implications for newly diagnosed cases of cancer given that excess body weight and abdominal adiposity are known to increase the risk of several cancers. The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to excess body weight and abdominal adiposity among Canadian adults. We estimated the population attributable risk (PAR) for all cancers associated with excess body weight and abdominal adiposity using contemporary cancer incidence, relative risk and exposure prevalence data for body mass index (BMI), waist circumference and waist-to-hip-ratio. Using the partial impact fraction (PIF), we also estimated the future avoidable burden of cancer from 2015 to 2042 in Canada, and by province, through various hypothetical intervention scenarios. In 2003, approximately half (50.5%) of the Canadian population was estimated to be overweight (BMI 25.0-29.9) or obese (BMI ≥30.0), 56.5% to have excess abdominal adiposity and 56.8% with a high waist-to-hip ratio. In 2015, the estimated PARs of all incident cancers associated with excess body weight, excess abdominal adiposity and high waist-to-hip ratio were 7.2%, 8.9% and 10.0%, respectively. If the population BMI could revert to its 1994 distribution, 72,157 associated cancer cases could be prevented cumulatively by 2042. A reduction in excess body weight and abdominal adiposity has the potential to decrease the future cancer burden in Canada substantially, and hence efforts to reverse increasing trends in obesity should be prioritized.

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.

The burden of cancer attributable to modifiable risk factors in Canada: Methods overview.

Up-to-date estimates of current and projected future cancer burden attributable to various exposures are essential for planning and implementing cancer prevention initiatives. The Canadian Population Attributable Risk of Cancer (ComPARe) study was conducted to: i) estimate the number and proportion of cancers diagnosed among adults in Canada in 2015 that are attributable to modifiable risk factors and ii) project the future avoidable cancers by 2042 under various intervention targets. We estimated the population attributable risk (with 95% confidence intervals) and the potential impact fraction of cancers associated with selected lifestyle, environmental, and infectious factors. Exposure-specific sensitivity analyses were also completed where appropriate. Several exposures of interest included active and passive smoking, obesity and abdominal adiposity, leisure-time physical inactivity, sedentary behaviour, alcohol consumption, insufficient fruit and vegetable intake, red and processed meat consumption, air pollution (PM2.5, NO2), indoor radon gas, ultraviolet radiation (UVR), hepatitis B and C virus, Helicobacter pylori, Epstein-Barr virus, human papillomavirus, human herpesvirus type 8 and human T-cell lymphotropic virus type 1. We used the 2015 cancer incidence data for 35 cancer sites from the Canadian Cancer Registry and projected cancer incidence to 2042 using historical data from 1983 to 2012. Here, we provide an overview of the data sources and methods used in estimating the current and future cancer burden in Canada. Specific methodologic details for each exposure are included in the individual articles included as part of this special issue.

Ovarian Carcinoma Histotype: Strengths and Limitations of Integrating Morphology With Immunohistochemical Predictions.

Ovarian carcinoma histotypes are critical for research and patient management and currently assigned by a combination of histomorphology +/- ancillary immunohistochemistry (IHC). We aimed to validate the previously described IHC algorithm (Calculator of Ovarian carcinoma Subtype/histotype Probability version 3, COSPv3) in an independent population-based cohort, and to identify problem areas for IHC predictions. Histotype was abstracted from cancer registries for eligible ovarian carcinoma cases diagnosed from 2002 to 2011 in Alberta and British Columbia, Canada. Slides were reviewed according to World Health Organization 2014 criteria, tissue microarrays were stained with and scored for the 8 COSPv3 IHC markers, and COSPv3 histotype predictions were calculated. Discordant cases for review and COSPv3 prediction were arbitrated by integrating morphology with IHC results. The integrated histotype (N=880) was then used to identify areas of inferior COSPv3 performance. Review histotype and integrated histotype demonstrated 93% agreement suggesting that IHC information revises expert review in up to 7% of cases. There was also 93% agreement between COSPv3 prediction and integrated histotype. COSPv3 errors predominated in 4 areas: endometrioid carcinoma (EC) versus clear cell (N=23), EC versus low-grade serous (N=15), EC versus high-grade serous (N=11), and high-grade versus low-grade serous (N=6). Most problems were related to Napsin A-negative clear cell, WT1-positive EC, and p53 IHC wild-type high-grade serous carcinomas. Although 93% of COSPv3 prediction accuracy was validated, some histotyping required integration of morphology with ancillary test results. Awareness of these limitations will avoid overreliance on IHC and misclassification of histotypes for research and clinical management.

Publicly funded healthcare costs associated with orofacial clefts for children born in Alberta, Canada between 2002 and 2018.

BACKGROUND: Orofacial clefts (OFCs) include cleft palate (CP), cleft lip (CL), and cleft lip with cleft palate (CLP) and require multidisciplinary healthcare services. Alberta, Canada has a publicly funded, universal access healthcare system. This study determined publicly funded healthcare costs for children with an OFC and compared these costs to children without congenital anomalies. METHODS: This retrospective population-based cohort analysis used the Alberta Congenital Anomalies Surveillance System to identify children born between 2002 and 2018 with an isolated OFC. They were matched 1:1 to a reference cohort based on sex and year of birth. The study population included 1614 children, from birth to 17 years of age linked to administrative databases to estimate annual inpatient and outpatient costs. Average annual all-cause costs were compared using two-sample independent t tests. RESULTS: The mean total cleft-related costs per patient were highest for children with CLP ($74,138 CAD, standard deviation (SD) $43,447 CAD), followed by CP ($53,062 CAD, SD $74,366 CAD), and CL ($35,288 CAD, SD $49,720 CAD). The mean total all-cause costs per child were statistically significantly higher (p < .001) in children with an OFC ($56,305 CAD, SD $57,744 CAD) compared to children without a congenital anomaly ($18,600 CAD, SD $61,300 CAD). CONCLUSIONS: Despite public health strategies to mitigate risk factors, the trend for OFCs has remained stable in Alberta, Canada for over 20 years. The costs reported are useful to other jurisdictions for comparison, and to families, healthcare professionals, service planners, and policy makers.

The Alberta Congenital Anomalies Surveillance System: a 40-year review with prevalence and trends for selected congenital anomalies, 1997-2019. / Le système de surveillance des anomalies congénitales de l'Alberta : compte rendu des données sur 40 ans avec prévalence et tendances de certaines anomalies congénitales entre 1997 et 2019.

INTRODUCTION: Current published long-term provincial or territorial congenital anomaly data are lacking for Canada. We report on prevalence (per 1000 total births) and trends in 1997-2019, in Alberta, Canada, for selected congenital anomalies. Associated risk factors are also discussed. METHODS: We used data from the Alberta Congenital Anomalies Surveillance System (ACASS) to calculate the prevalence and perform chi-square linear trend analyses. RESULTS: From 1997 to 2019, the overall prevalence of neural tube defects was stable, at 0.74 per 1000 total births. The same was true for spina bifida (0.38), orofacial clefts (1.99), more severe CHDs (transposition of the great arteries, 0.38; tetralogy of Fallot, 0.33; and hypoplastic left heart syndrome, 0.32); and gastroschisis (0.38). Anencephaly, cleft palate and anorectal malformation significantly decreased with a prevalence of 0.23, 0.75 and 0.54 per 1000 total births, respectively. Significantly increasing trends were reported for anotia/microtia (0.24), limb reduction anomalies (0.73), omphalocele (0.36) and Down syndrome (2.21) and for hypospadias and undescended testes (4.68 and 5.29, respectively, per 1000 male births). CONCLUSION: Congenital anomalies are an important public health concern with significant social and societal costs. Surveillance data gathered by ACASS for over 40 years can be used for planning and policy decisions and the evaluation of prevention strategies. Contributing genetic and environmental factors are discussed as is the need for continued surveillance and research.

Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma.

CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high-level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut-off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high-level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut-off for IHC to predict CCNE1 high-level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high-level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high-level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38-2.26, p < 0.0001). CCNE1 high-level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high-level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors.

Estimating the current and future cancer burden in Canada: methodological framework of the Canadian population attributable risk of cancer (ComPARe) study.

INTRODUCTION: The Canadian Population Attributable Risk of Cancer project aims to quantify the number and proportion of cancer cases incident in Canada, now and projected to 2042, that could be prevented through changes in the prevalence of modifiable exposures associated with cancer. The broad risk factor categories of interest include tobacco, diet, energy imbalance, infectious diseases, hormonal therapies and environmental factors such as air pollution and residential radon. METHODS AND ANALYSIS: Using a national network, we will use population-attributable risks (PAR) and potential impact fractions (PIF) to model both attributable (current) and avoidable (future) cancers. The latency periods and the temporal relationships between exposures and cancer diagnoses will be accounted for in the analyses. For PAR estimates, historical exposure prevalence data and the most recent provincial and national cancer incidence data will be used. For PIF estimates, we will model alternative or 'counterfactual' distributions of cancer risk factor exposures to assess how cancer incidence could be reduced under different scenarios of population exposure, projecting incidence to 2042. DISSEMINATION: The framework provided can be readily extended and applied to other populations or jurisdictions outside of Canada. An embedded knowledge translation and exchange component of this study with our Canadian Cancer Society partners will ensure that these findings are translated to cancer programmes and policies aimed at population-based cancer risk reduction strategies.

Cancer incidence attributable to lifestyle and environmental factors in Alberta in 2012: summary of results.

BACKGROUND: Estimates of the proportion of cancer cases that can be attributed to modifiable risk factors are not available for Canada and, more specifically, Alberta. The purpose of this study was to estimate the total proportion of cancer cases in Alberta in 2012 that could be attributed to a set of 24 modifiable lifestyle and environmental risk factors. METHODS: We estimated summary population attributable risk estimates for 24 risk factors (smoking [both passive and active], overweight and obesity, inadequate physical activity, diet [inadequate fruit and vegetable consumption, inadequate fibre intake, excess red and processed meat consumption, salt consumption, inadequate calcium and vitamin D intake], alcohol, hormones [oral contraceptives and hormone therapy], infections [Epstein-Barr virus, hepatitis B and C viruses, human papillomavirus, Helicobacter pylori], air pollution, natural and artificial ultraviolet radiation, radon and water disinfection by-products) by combining population attributable risk estimates for each of the 24 factors that had been previously estimated. To account for the possibility that individual cancer cases were the result of a combination of multiple risk factors, we subtracted the population attributable risk for the first factor from 100% and then applied the population attributable risk for the second factor to the remaining proportion that was not attributable to the first factor. We repeated this process in sequential order for all relevant exposures. RESULTS: Overall, an estimated 40.8% of cancer cases in Alberta in 2012 were attributable to modifiable lifestyle and environmental risk factors. The largest proportion of cancers were estimated to be attributable to tobacco smoking, physical inactivity and excess body weight. The summary population attributable risk estimate was slightly higher among women (42.4%) than among men (38.7%). INTERPRETATION: About 41% of cancer cases in Alberta may be attributable to known modifiable lifestyle and environmental risk factors. Reducing the prevalence of these factors in the Alberta population has the potential to substantially reduce the provincial cancer burden.

Cancer incidence attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012.

BACKGROUND: Hormonal contraceptives and hormone replacement therapies are classified as carcinogenic to humans (group 1) by the International Agency for Research on Cancer. We sought to estimate the proportion and total number of cancers attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012. METHODS: Population attributable risks were used to estimate the proportion of attributable cases for each associated cancer site. Relative risk estimates were obtained from the most relevant and recent epidemiologic literature. Prevalences of the use of oral contraceptives and hormone therapy in Alberta were collected from Alberta's Tomorrow Project. Specific cancer incidence data were obtained from the Alberta Cancer Registry for the year 2012. RESULTS: Overall, 6.3% of breast cancers (n = 135) diagnosed in Alberta in 2012 were estimated to be attributable to the use of oral contraceptives, and the exposure potentially prevented about 57.3% of endometrial cancers (n = 276) and 29.1% of ovarian cancers (n = 52). About 15.5% of breast cancers (n = 258) and 8.9% of ovarian cancers (n = 13) were estimated to be attributable to the use of hormone therapy, whereas 11.3% of endometrial cancers (n = 48) were possibly prevented by the exposure. INTERPRETATION: Based on our estimates, oral contraceptive use resulted in a net protective effect among the cancer sites studied, thus reducing the cancer burden in Alberta in 2012. The use of hormone therapy was estimated to increase the cancer burden in the province, therefore the risk and benefit of hormone therapy should be carefully considered before use.