Abstract
Background
Esophageal cancer can be subdivided into two main histological subtypes with significant variability in their etiology and epidemiology. The incidence of esophageal adenocarcinoma (AC) is increasing across the developed countries, whereas the incidence of esophageal squamous cell carcinoma (SCC) is declining. Several risk factors have been identified in the pathogenesis of each subtype, however, their epidemiologic characteristics and distribution throughout Canada remain poorly understood.
Methods
We performed a retrospective analysis of demographic data across Canada from 1992 to 2010 using two independent population‐based cancer registries. The incidence of esophageal cancer, for each subtype, was examined at the levels of provinces/territories, cities, and postal codes.
Results
A total of 19 790 patients were diagnosed with esophageal cancer in Canada between 1992 and 2010; 74% were males. The average national incidence rate was 33.5 cases per million individuals per year. Incidence of esophageal AC increased over time, with notable high‐incidence rates on the Vancouver Island, the coasts of the Great Lakes, and the coasts of the Northumberland Strait in the Maritimes. The overall incidence of esophageal SCC has decreased. However, high incidence of esophageal SCC was detected in the Vancouver city, rural eastern Québec, and in the Maritimes. We also report clustering for each subtype using postal codes, which sheds light onto new avenues of research for potential environmental etiologies.
Conclusions
This study, for the first time, provides a detailed analysis on the burden of esophageal cancer in Canada, revealing important geographic clustering trends.
Keywords: Barrett's esophagus, Canada, epidemiology, esophageal adenocarcinoma, esophageal cancer, esophageal squamous cell carcinoma, gastroesophageal reflux disease (GERD), geographic clustering, great lakes, incidence, obesity, pollution, risk factors, smoking
We demonstrate clustering of esophageal adenocarcinoma in three areas of Canada (in the Maritime provinces, around the great lakes, and in British Columbia) mirroring results from a recent report in the United States. In these regions, certain lifestyle factors and environmental pollutants may play an important role in pathogenesis. Clustering of esophageal Squamous Cell Carcinoma was primarily demonstrated in British Columbia which is home to a significant community of Southeast Asian immigrants.
1. INTRODUCTION
Esophageal cancer has two main histological subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC).1 Esophageal SCC is the most common of the two, representing 87% of all esophageal neoplasms in 2012.2 While esophageal SCC is more common in the developing countries, esophageal AC has become much more predominant across the western world.3 There exist many epidemiological differences between the two subtypes, however, these have not been explicitly defined on a global level until in 2014; a study by Arnold et al investigated worldwide trends of esophageal cancer incidence by histological type, reporting a global esophageal SCC incidence of 52 cases per million individuals per year, with the male predominance of 2.7 to 1.2 The majority (80%) of cases of esophageal SCC occurred in central and southeast Asia, with only 1.8% of cases reported in North America.2 The etiology of esophageal SCC is closely linked to alcohol and tobacco use.4 SEER data for esophageal SCC incidence in the United States examined between 1992 and 2013 demonstrated a decreasing incidence over time, from 51 cases to 26 cases per million individuals per year.5
Global esophageal AC affects 7 individuals per million per year with a predilection for the male gender at a ratio of 4.4:1.2 The majority of cases (22.8%) occurred in the northwestern Europe, with Southeast Asia and North America close behind.2 Within these regions, the incidence rates were much higher and favored the male gender with 8.5:1 incidence rate ratio.2 AC originates from Barrett's esophagus, in which normal squamous mucosa of the lower third of the esophagus undergoes dysplasia and is replaced by columnar cells resembling intestinal mucosa.6 The two most recognized risk factors for esophageal AC are gastroesophageal reflux disease and obesity.7, 8 While the incidence rates of several cancers have been decreasing, the incidence rate of esophageal AC has risen sixfold in the United States since 1970.6 Data from 13 European countries between 1983 and 1997 reported similar trends.9
In Canada, there have been limited studies reporting on rising rates of esophageal cancer in Ontario and in British Columbia in recent years.10, 11, 12 In this study, we conducted an extensive epidemiological analysis on the burden of esophageal cancer for both subtypes across all provinces and territories in Canada during the period 1992‐2010. The geographic distribution of these patients was analyzed, with the aim to better understand risk factors related to the pathogenesis of this neoplasm and to identify communities at high vs low risk for esophageal cancer.
2. METHODS
This study was conducted in accordance with the CISS‐RDC‐668035 and 13‐SSH‐MCG‐3749‐S001 protocols approved by the Social Sciences and Humanities Research Council of Canada (SSHRC) and the Québec Inter‐University Centre for Social Statistics (QICSS), respectively. This study was exempt from the McGill University Research Ethics Board review. The data on esophageal cancer incidence was examined using two distinct population‐based cancer databases: the Canadian Cancer Registry (CCR) and Le Registre Québécois du Cancer (LRQC) during 1992‐2010. International Classification of Disease for Oncology ICD‐O‐3 codes were used for five subtypes of esophageal AC, and three subtypes of esophageal SCC, similarly as reported in our previous studies.13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 Due to space limitations, detailed methods are provided in the Appendix S1.
3. RESULTS
A general overview of demographic characteristics for esophageal cancer and its two histologic subtypes are presented in Table 1. In total, 19 790 patients were diagnosed with esophageal cancer. The majority (74%) were males, while 26% were females, with a male:female IRR of 2.9:1.0. The average age of diagnosis was 67.5 ± 0.8 years, with 92% of patients being > 60. The crude annual incidence of esophageal cancer showed a steady upward trend (Figure 1A); in 1992 the incidence rate was of 29.1 cases per million individuals per year; in 2010 this value had risen to 41.5, representing an increase of 43% over 19 years. The average national incidence rate for esophageal cancer between 1992 and 2010 was 33.5 cases per million individuals per year. The age‐standardized national incidence rate was 23.0 cases per year. Geographic analysis of esophageal cancer trends throughout the country is presented in Figure 1B,C. On the provincial level, Prince Edward Island (PEI), Nova Scotia (NS), New Brunswick (NB), and British Columbia (BC) had significantly higher annual age‐standardized incidence rates than that of the national average, of up to 45.7 cases per million individuals in PEI. In contrast, Newfoundland and Labrador and Quebec (QC) had significantly lower incidence rates.
Table 1.
Epidemiologic characteristics of esophageal cancer and its two major histological subtypes between 1992 and 2010
| A: Incidence by sex | ||||||
|---|---|---|---|---|---|---|
| Subtype | Number of males | % of females | Number of females | % females | Average crude incidence rate in # cases per million individuals per year and (95% confidence intervals) | Average ASIR in # cases per million individuals per year and (95% confidence intervals) |
| Esophageal Cancer | 14 635 | 70.01 | 5140 | 25.99 | 33.49 (33.02‐33.96) | 23.01 (22.62‐23.40) |
| Esophageal AC | 9005 | 84.36 | 1670 | 15.64 | 18.08 (17.74‐18.43) | 12.59 (12.30‐12.89) |
| Esophageal SCC | 5630 | 61.87 | 3470 | 38.13 | 15.41 (15.09‐15.73) | 10.42 (10.16‐10.69) |
| B: Incidence by age group | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subtype | <30 | 30‐39 | 40‐49 | 50‐59 | 60‐69 | 70‐79 | 80‐89 | 90+ | Average age of diagnosis |
| Esophageal Cancer | 0 | 3.03 | 13.42 | 38.89 | 85.68 | 144.51 | 129.13 | 58.88 | 67.52 ± 0.76 |
| Esophageal AC | 0 | 2.31 | 9.32 | 23.16 | 43.95 | 73.65 | 64.50 | 26.44 | 66.40 ± 1.01 |
| Esophageal SCC | 0 | 0.73 | 4.11 | 15.74 | 41.74 | 70.86 | 63.63 | 32.44 | 68.30 ± 1.14 |
Figure 1.
Incidence of esophageal cancer throughout Canada between 1992 and 2010 over time and by province (in cases per million individuals per year). A. Changing incidence rates for esophageal cancer between 1992 and 2010. Linear regression analysis of incidence rates over time [R2] = 0.86; P = .002. The slope of the line was 0.69 cases per million individuals per year. Dotted lines indicate 95% confidence interval. B. Age‐standardized incidence rates of esophageal cancer across Canadian provinces between 1992 and 2010. *Statistically significant lower incidence rates (P < .05) compared to the Canadian average. **Statistically significant higher incidence rates (P < .05) compared to the Canadian average. C. Esophageal cancer incidence trends by province in Canada. Geographic maps illustrate age‐standardized incidence rates of esophageal cancer relative to the national average based on the Canadian Cancer Registry/ Le Registre Québecois du Cancer databases
Incidence rates for Canadian cities corroborated these trends and revealed certain clustering of cases throughout the country, as seen in Tables S1A,B and Figure S1. Of the 20 cities with high incidence of esophageal cancer, 10 (50%) were in Ontario (ON), 9 (45%) were in BC, and 1 (5%) was in Saskatchewan (SK). In contrast, of the 20 low‐incidence cities in Canada, 11 (55%) were located in QC, which also had a significantly lower provincial incidence rate than the rest of Canada. On further assessment, 8/11 of low‐incidence cities in QC were part of the Greater Montreal Area. We were able to observe high incidence areas on the Vancouver Island (BC), and in Southern Ontario, which encompasses Eastern, Central, and Western Ontario (Figure S1A).
Subsequently, the distribution of esophageal cancer patients was examined within cities by analyzing individual Forward Sortation Areas (FSAs). Each FSA corresponds to an area where all postal codes share the first three entries (eg, H4A). There are 1648 FSAs in Canada; 15.7% (258/1648) of these FSAs were excluded from this study as their populations were less than 5000, as per Statistics Canada regulations. High concentration of esophageal cancer cases was observed on the Vancouver Island, in Eastern Ontario, Newfoundland's Avalon Peninsula, and surrounding the Northumberland Strait on the coasts of PEI and Nova Scotia (Table S2A; Figure S1B). Several statistically‐significant zero‐incidence FSAs were also identified; areas in which zero cases of esophageal cancer had been recorded between 1992 and 2010. These 18 FSAs are presented in Table S2B, with the majority being located in Central Ontario and in the Greater Toronto Area (GTA).
3.1. Analysis of esophageal adenocarcinoma
Esophageal AC was diagnosed in 10 675 Canadians between 1992 and 2010, of which 84.4% of patients were male and the average age at the time of diagnosis was 66.4 ± 1.0 years (Table 1). The crude average incidence rate for esophageal AC was 18.1 cases per million individuals per year. In 1992, the incidence rate of esophageal AC was 10.9 cases per million individuals per year. By 2010 this value had risen to 26.8 cases, representing > 2‐fold increase over 19 years (Figure 2A). The age‐standardized national incidence rate was 12.6 cases per year.
Figure 2.
Incidence of esophageal cancer subtypes throughout Canada between 1992 and 2010 over time and by province (in cases per million individuals per year). A. Changing incidence rates for esophageal adenocarcinoma between 1992 and 2010. Linear regression analysis of incidence rates over time [R2] = 0.95; P = .002. The slope of the line was 0.87 cases per million individuals per year. Dotted lines indicate 95% confidence interval. B. Age‐standardized incidence rates of esophageal adenocarcinoma across Canadian provinces between 1992 and 2010. *Statistically significant lower incidence rate (P < .05) compared to Canadian average. **Statistically significant higher incidence rates (P < .05) compared to Canadian average. C. Changing incidence rates for esophageal squamous cell carcinoma between 1992 and 2010. Linear regression analysis incidence rate over time [R2] = 0.74; P = .002. The slope of the line was −0.19 cases per million individuals per year. Dotted lines indicate 95% confidence interval. D. Age‐standardized incidence rates of esophageal squamous cell carcinoma (per 1 million individuals per year) in the Canadian provinces between 1992 and 2010. *Statistically significant lower incidence rate (P < .05) compared to Canadian average. **Statistically significant higher incidence rates (P < .05) compared to Canadian average
On the provincial level, PEI, NS, NB, and BC had significantly higher incidence rates than the national average, of up to 29.4 cases per million individuals per year in the PEI (Figure 2B). In contrast, MB, NF, and QC had significantly lower incidence rates. Incidence rates for Canadian cities corroborated these trends and revealed patient clusters (Tables S3A,B). The distribution of esophageal AC patients within cities by FSA is presented in Table 2, and Figure 3. A notably high incidence was found for the FSA V8L, representing a borough within the city of Sidney, in North Saanich on the Vancouver Island, with the rate of 71.2 cases per million individuals per year, fourfold higher than the national average. The city of Sidney was also recorded as the city with the highest incidence of esophageal AC in Canada (95.4 cases per million individuals per year). Three clusters of esophageal AC cases were found, in the west coast of BC, rural eastern ON, and in the Maritimes surrounding Northumberland Strait. These results are further discussed in Appendix S2.
Table 2.
List of Populous Forward Sortation Areas (FSA) in Canada with high crude incidence rates of esophageal adenocarcinoma from 1992 to 2010. All population numbers are rounded to the nearest thousand
| FSA | Province | Cases | Average Population | Crude incidence per million individuals per year | Lower 95% CI | Higher 95% CI |
|---|---|---|---|---|---|---|
| B0E | NS | 20 | 30 000 | 34.97 | 21.36 | 54.01 |
| B0K | NS | 30 | 38 000 | 41.13 | 27.75 | 58.71 |
| B0N | NS | 30 | 44 000 | 36.15 | 24.39 | 51.60 |
| B0T | NS | 15 | 17 000 | 47.73 | 26.71 | 78.73 |
| B0W | NS | 25 | 33 000 | 39.49 | 25.56 | 58.29 |
| B1H | NS | 10 | 11 000 | 48.78 | 23.39 | 89.70 |
| B2N | NS | 20 | 29 000 | 36.45 | 22.26 | 56.29 |
| B2T | NS | 10 | 14 000 | 38.99 | 18.70 | 71.70 |
| B3A | NS | 15 | 20 000 | 38.62 | 21.62 | 63.70 |
| B3N | NS | 10 | 12 000 | 43.57 | 20.89 | 80.13 |
| B3P | NS | 10 | 8000 | 62.36 | 29.90 | 114.68 |
| B3Z | NS | 10 | 11 000 | 48.96 | 23.48 | 90.04 |
| C0A | PEI | 25 | 43 000 | 30.32 | 19.62 | 44.77 |
| C1A | PEI | 25 | 31 000 | 42.17 | 27.29 | 62.26 |
| E1N | NB | 10 | 11 000 | 47.54 | 22.80 | 87.44 |
| E2J | NB | 20 | 16 000 | 66.71 | 40.75 | 103.02 |
| E2M | NB | 15 | 19 000 | 41.27 | 23.10 | 68.07 |
| E3A | NB | 20 | 27 000 | 38.40 | 23.46 | 59.31 |
| E3V | NB | 10 | 12 000 | 42.17 | 20.22 | 77.56 |
| E5N | NB | 10 | 11 000 | 46.70 | 22.39 | 85.88 |
| E7M | NB | 10 | 10 000 | 54.26 | 26.02 | 99.78 |
| G1H | QC | 20 | 29 000 | 36.41 | 22.24 | 56.23 |
| G1M | QC | 15 | 18 000 | 44.45 | 24.88 | 73.32 |
| G6G | QC | 15 | 20 000 | 38.66 | 21.64 | 63.77 |
| J1H | QC | 20 | 29 000 | 36.88 | 22.53 | 56.96 |
| J6S | QC | 15 | 23 000 | 34.58 | 19.35 | 57.04 |
| K0A | ON (Eastern) | 50 | 91 000 | 28.76 | 21.35 | 37.92 |
| K0C | ON (Eastern) | 30 | 51 000 | 30.92 | 20.86 | 44.14 |
| K0E | ON (Eastern) | 35 | 39 000 | 47.83 | 33.32 | 66.53 |
| K0G | ON (Eastern) | 20 | 33 000 | 31.51 | 19.24 | 48.66 |
| K0H | ON (Eastern) | 30 | 42 000 | 37.49 | 25.29 | 53.51 |
| K0K | ON (Eastern) | 75 | 103 000 | 38.23 | 30.07 | 47.93 |
| K0L | ON (Eastern) | 50 | 68 000 | 38.52 | 28.59 | 50.78 |
| K0M | ON (Eastern) | 40 | 46 000 | 45.39 | 32.43 | 61.81 |
| K2A | ON (Eastern) | 15 | 15 000 | 51.16 | 28.64 | 84.39 |
| K6H | ON (Eastern) | 25 | 29 000 | 44.75 | 28.96 | 66.07 |
| K6V | ON (Eastern) | 25 | 28 000 | 46.33 | 29.98 | 68.39 |
| K7G | ON (Eastern) | 10 | 8000 | 63.03 | 30.23 | 115.92 |
| K7K | ON (Eastern) | 20 | 31 000 | 34.46 | 21.05 | 53.21 |
| K7L | ON (Eastern) | 15 | 21 000 | 38.12 | 21.34 | 62.87 |
| K7M | ON (Eastern) | 35 | 45 000 | 40.76 | 28.39 | 56.69 |
| K7S | ON (Eastern) | 10 | 12 000 | 44.57 | 21.37 | 81.96 |
| K8N | ON (Eastern) | 20 | 26 000 | 39.89 | 24.36 | 61.60 |
| K8P | ON (Eastern) | 15 | 20 000 | 38.53 | 21.56 | 63.55 |
| K8V | ON (Eastern) | 20 | 27 000 | 39.17 | 23.93 | 60.50 |
| K9H | ON (Eastern) | 25 | 26 000 | 50.47 | 32.66 | 74.51 |
| K9J | ON (Eastern) | 35 | 45 000 | 41.18 | 28.69 | 57.28 |
| K9V | ON (Eastern) | 20 | 25 000 | 42.41 | 25.91 | 65.50 |
| L0K | ON (Central) | 20 | 33 000 | 32.19 | 19.66 | 49.72 |
| L0P | ON (Central) | 10 | 11 000 | 47.76 | 22.90 | 87.83 |
| L2E | ON (Central) | 15 | 21 000 | 36.87 | 20.64 | 60.82 |
| L2N | ON (Central) | 20 | 32 000 | 33.35 | 20.37 | 51.51 |
| L2P | ON (Central) | 10 | 13 000 | 39.04 | 18.72 | 71.80 |
| L3V | ON (Central) | 25 | 41 000 | 32.01 | 20.71 | 47.25 |
| L7N | ON (Central) | 15 | 13 000 | 61.29 | 34.31 | 101.10 |
| L8L | ON (Central) | 20 | 34 000 | 31.40 | 19.18 | 48.50 |
| L8P | ON (Central) | 15 | 22 000 | 35.79 | 20.03 | 59.03 |
| L8T | ON (Central) | 15 | 19 000 | 40.97 | 22.93 | 67.57 |
| L8V | ON (Central) | 15 | 22 000 | 36.69 | 20.53 | 60.51 |
| L9A | ON (Central) | 15 | 23 000 | 33.71 | 18.87 | 55.60 |
| L9H | ON (Central) | 25 | 31 000 | 42.44 | 27.47 | 62.66 |
| N0A | ON (Western) | 20 | 30 000 | 35.56 | 18.47 | 42.14 |
| N0H | ON (Western) | 25 | 45 000 | 29.32 | 21.72 | 54.92 |
| N1A | ON (Western) | 10 | 12 000 | 44.19 | 18.97 | 43.28 |
| N2H | ON (Western) | 15 | 21 000 | 37.45 | 20.96 | 61.77 |
| N3B | ON (Western) | 10 | 10 000 | 50.85 | 24.39 | 93.52 |
| N3Y | ON (Western) | 15 | 22 000 | 36.03 | 20.17 | 59.43 |
| N4N | ON (Western) | 10 | 9000 | 56.35 | 27.02 | 103.63 |
| N4W | ON (Western) | 10 | 10 000 | 54.15 | 25.97 | 99.58 |
| N5C | ON (Western) | 10 | 14 000 | 38.96 | 18.68 | 71.64 |
| N7A | ON (Western) | 10 | 12 000 | 45.06 | 21.61 | 82.87 |
| N7T | ON (Western) | 20 | 27 000 | 38.91 | 23.77 | 60.10 |
| N8S | ON (Western) | 15 | 23 000 | 34.49 | 19.30 | 56.89 |
| P0B | ON (Northern) | 10 | 8000 | 62.51 | 29.97 | 114.95 |
| P1B | ON (Northern) | 20 | 34 000 | 30.72 | 18.77 | 47.45 |
| P2N | ON (Northern) | 10 | 8000 | 65.87 | 31.59 | 121.14 |
| P4N | ON (Northern) | 20 | 28 000 | 37.04 | 22.62 | 57.20 |
| P5A | ON (Northern) | 10 | 12 000 | 43.39 | 20.81 | 79.80 |
| P6B | ON (Northern) | 15 | 24 000 | 33.42 | 18.71 | 55.13 |
| P7B | ON (Northern) | 25 | 30 000 | 43.67 | 28.26 | 64.47 |
| P7C | ON (Northern) | 25 | 29 000 | 45.23 | 29.27 | 66.77 |
| P7E | ON (Northern) | 15 | 22 000 | 35.79 | 20.03 | 59.03 |
| R2Y | MB | 15 | 20 000 | 39.28 | 21.98 | 64.78 |
| S0E | SK | 20 | 34 000 | 30.56 | 18.67 | 47.20 |
| S0L | SK | 20 | 32 000 | 32.82 | 20.05 | 50.69 |
| S4P | SK | 10 | 12 000 | 42.17 | 20.22 | 77.56 |
| S6H | SK | 25 | 30 000 | 44.20 | 28.60 | 65.25 |
| T2E | AB | 20 | 32 000 | 32.94 | 20.12 | 50.87 |
| V0E | BC | 45 | 65 000 | 36.70 | 26.77 | 49.10 |
| V0H | BC | 35 | 51 000 | 36.13 | 25.17 | 50.25 |
| V0R | BC | 45 | 64 000 | 36.92 | 26.93 | 49.40 |
| V0X | BC | 15 | 20 000 | 39.55 | 22.14 | 65.24 |
| V1C | BC | 15 | 24 000 | 33.28 | 18.63 | 54.90 |
| V1J | BC | 15 | 22 000 | 36.30 | 20.32 | 59.87 |
| V1T | BC | 20 | 31 000 | 33.91 | 20.71 | 52.37 |
| V1Y | BC | 20 | 32 000 | 32.93 | 20.11 | 50.85 |
| V2A | BC | 25 | 35 000 | 37.55 | 24.30 | 55.43 |
| V2B | BC | 30 | 36 000 | 44.23 | 29.84 | 63.14 |
| V2P | BC | 25 | 33 000 | 39.29 | 25.43 | 58.00 |
| V2S | BC | 25 | 44 000 | 29.59 | 19.15 | 43.69 |
| V3A | BC | 25 | 40 000 | 32.79 | 21.22 | 48.40 |
| V3L | BC | 15 | 23 000 | 34.61 | 19.37 | 57.09 |
| V4A | BC | 20 | 35 000 | 30.19 | 18.44 | 46.62 |
| V4K | BC | 15 | 24 000 | 33.42 | 18.71 | 55.13 |
| V4P | BC | 10 | 12 000 | 45.65 | 21.89 | 83.95 |
| V4T | BC | 15 | 21 000 | 37.92 | 21.22 | 62.54 |
| V8A | BC | 20 | 18 000 | 58.71 | 35.86 | 90.67 |
| V8L | BC | 30 | 22 000 | 71.16 | 48.01 | 101.58 |
| V8R | BC | 15 | 23 000 | 34.78 | 19.47 | 57.36 |
| V8V | BC | 15 | 24 000 | 33.21 | 18.59 | 54.78 |
| V8X | BC | 15 | 22 000 | 35.21 | 19.71 | 58.08 |
| V8Z | BC | 25 | 27 000 | 48.46 | 31.36 | 71.54 |
| V9A | BC | 25 | 35 000 | 37.85 | 24.50 | 55.88 |
| V9B | BC | 20 | 32 000 | 32.56 | 19.89 | 50.28 |
| V9G | BC | 10 | 10 000 | 50.56 | 24.24 | 92.98 |
| V9K | BC | 10 | 14 000 | 38.90 | 18.65 | 71.54 |
| V9N | BC | 20 | 27 000 | 38.35 | 23.42 | 59.22 |
| V9P | BC | 20 | 21 000 | 51.35 | 31.36 | 79.30 |
| V9S | BC | 15 | 16 000 | 50.87 | 28.47 | 83.90 |
Figure 3.
Esophageal adenocarcinoma incidence trends by FSA in Canada. Geographic maps illustrating incidence rates of esophageal adenocarcinoma (cases per million individuals per year) relative to the national average based on the Canadian Cancer Registry/ Le Registre Québécois du Cancer databases. A: Esophageal adenocarcinoma incidence trends by FSA in British Columbia (BC). This figure includes the highest incidence FSA, V8L in Sidney, North Saanich, BC. B: Esophageal adenocarcinoma incidence trends by FSA in Ontario. This figure shows high incidence esophageal adenocarcinoma FSAs in Eastern Ontario surrounding Lake Ontario. C: Esophageal adenocarcinoma incidence trends by FSA in the Maritimes. This figure shows high incidence esophageal adenocarcinoma FSAs in Nova Scotia and PEI
3.2. Analysis of esophageal squamous cell carcinoma
Esophageal SCC was diagnosed in 9115 Canadians between 1992 and 2010, with 61.9% male patients, and an average age at diagnosis of 68.3 ± 1.1 years (Table 1). The crude average incidence rate for esophageal SCC was 15.4 cases per million individuals per year. In 1992, the incidence rate was 18.2 cases per million individuals per year. In 2010, this value had decreased to 14.7 cases, representing a 19% decrease over 19 years (Figure 2C). The age‐standardized national incidence rate was 10.4 cases per year. On the provincial level (Figure 2D), only BC exhibited significantly higher incidence rates than the national average (18.6 cases per million individuals per year). In contrast, QC had a significantly lower incidence rate of 14.4 cases per million individuals per year. Analysis by FSA (Table 3 and Figure 4A) showed a notable high‐incidence in V6A postal code, a borough within the Vancouver city, encompassing Strathcona, Chinatown and Downtown Eastside (DTES) with a rate of 63.7 cases per million individuals per year, approximately four times higher than the national average. Significant clusters of esophageal SCC cases were found in the west coast of BC, rural QC and NB, and in the Maritimes. Results at the city and FSA levels are further discussed in Appendix S2 and can be viewed in Figure 4A‐D.
Table 3.
List of Populous Forward Sortation Areas (FSA) in Canada with high crude incidence rates of esophageal squamous cell carcinoma from 1992 to 2010
| FSA | Province | Cases | Average population | Crude incidence per million individuals per year | Lower 95% CI | Higher 95% CI |
|---|---|---|---|---|---|---|
| A0B | NF | 15 | 23 610 | 33.44 | 18.70 | 55.15 |
| A1C | NF | 10 | 14 280 | 36.86 | 17.64 | 67.79 |
| B0C | NS | 5 | 5300 | 49.65 | 16.00 | 115.87 |
| B0K | NS | 20 | 38 390 | 27.42 | 16.74 | 42.35 |
| B1P | NS | 10 | 16 060 | 32.77 | 15.69 | 60.27 |
| B1V | NS | 5 | 7020 | 37.49 | 12.08 | 87.48 |
| B2G | NS | 10 | 14 080 | 37.38 | 17.90 | 68.75 |
| E3A | NB | 15 | 27 410 | 28.80 | 16.11 | 47.51 |
| E7C | NB | 5 | 5500 | 47.85 | 15.42 | 111.66 |
| G0E | QC | 10 | 11 790 | 44.64 | 21.37 | 82.10 |
| G0K | QC | 10 | 13 200 | 39.87 | 19.09 | 73.33 |
| G1J | QC | 20 | 22 810 | 46.15 | 28.18 | 71.28 |
| G1K | QC | 15 | 18 270 | 43.21 | 24.17 | 71.28 |
| G1L | QC | 15 | 22 920 | 34.44 | 19.26 | 56.82 |
| G1R | QC | 15 | 16 710 | 47.25 | 26.42 | 77.93 |
| H1H | QC | 20 | 34 700 | 30.34 | 18.52 | 46.85 |
| H1M | QC | 15 | 27 510 | 28.70 | 16.05 | 47.34 |
| H2H | QC | 10 | 13 920 | 37.81 | 18.10 | 69.54 |
| H2K | QC | 15 | 27 080 | 29.15 | 16.30 | 48.09 |
| H4H | QC | 15 | 19 480 | 40.53 | 22.67 | 66.85 |
| H8N | QC | 15 | 26 490 | 29.80 | 16.67 | 49.16 |
| H8P | QC | 15 | 22 410 | 35.23 | 19.70 | 58.11 |
| H9S | QC | 15 | 21 540 | 36.65 | 20.50 | 60.46 |
| J2K | QC | 10 | 14 570 | 36.12 | 17.29 | 66.44 |
| J7Z | QC | 15 | 28 270 | 27.93 | 15.62 | 46.06 |
| J8X | QC | 10 | 10 900 | 48.29 | 23.12 | 88.81 |
| K0J | ON (Eastern) | 20 | 33 120 | 31.78 | 19.41 | 49.09 |
| K2A | ON (Eastern) | 15 | 15 430 | 51.16 | 28.62 | 84.39 |
| K2B | ON (Eastern) | 20 | 33 050 | 31.85 | 19.45 | 49.19 |
| K2C | ON (Eastern) | 15 | 27 040 | 29.20 | 16.33 | 48.16 |
| K2P | ON (Eastern) | 10 | 14 810 | 35.54 | 17.01 | 65.36 |
| K6V | ON (Eastern) | 20 | 28 400 | 37.06 | 22.63 | 57.25 |
| K7A | ON (Eastern) | 10 | 16 640 | 31.63 | 15.14 | 58.17 |
| K7C | ON (Eastern) | 10 | 15 160 | 34.72 | 16.62 | 63.85 |
| K7H | ON (Eastern) | 10 | 14 520 | 36.25 | 17.35 | 66.67 |
| K8N | ON (Eastern) | 15 | 26 390 | 29.92 | 16.73 | 49.34 |
| K9J | ON (Eastern) | 30 | 44 730 | 35.30 | 23.81 | 50.39 |
| L2A | ON (Central) | 10 | 16 200 | 32.49 | 15.55 | 59.75 |
| L4Y | ON (Central) | 15 | 24 090 | 32.77 | 18.33 | 54.06 |
| L6K | ON (Central) | 10 | 12 650 | 41.61 | 19.92 | 76.52 |
| L6L | ON (Central) | 15 | 26 320 | 30.00 | 16.78 | 49.48 |
| L6T | ON (Central) | 20 | 38 980 | 27.00 | 16.49 | 41.71 |
| L7L | ON (Central) | 20 | 36 720 | 28.67 | 17.50 | 44.28 |
| L7N | ON (Central) | 10 | 12 880 | 40.86 | 19.56 | 75.15 |
| M4G | ON (Toronto) | 10 | 16 260 | 32.37 | 15.50 | 59.53 |
| M4V | ON (Toronto) | 10 | 16 380 | 32.13 | 15.38 | 59.10 |
| M6N | ON (Toronto) | 25 | 41 110 | 32.01 | 20.71 | 47.25 |
| M9N | ON (Toronto) | 15 | 23 880 | 33.06 | 18.49 | 54.53 |
| N0M | ON (Western) | 30 | 64 370 | 24.53 | 16.55 | 35.02 |
| N2G | ON (Western) | 10 | 13 490 | 39.02 | 18.68 | 71.76 |
| N3T | ON (Western) | 15 | 26 310 | 30.01 | 16.78 | 49.49 |
| N5A | ON (Western) | 20 | 30 420 | 34.60 | 21.13 | 53.44 |
| N6A | ON (Western) | 10 | 10 850 | 48.51 | 23.22 | 89.21 |
| N6B | ON (Western) | 10 | 9970 | 52.79 | 25.27 | 97.09 |
| N7A | ON (Western) | 10 | 11 680 | 45.06 | 21.57 | 82.88 |
| N8X | ON (Western) | 10 | 16 280 | 32.33 | 15.48 | 59.46 |
| N9A | ON (Western) | 20 | 27 120 | 38.81 | 23.70 | 59.95 |
| P0H | ON (Northern) | 20 | 34 630 | 30.40 | 18.56 | 46.95 |
| P0K | ON (Northern) | 10 | 12 270 | 42.89 | 20.54 | 78.89 |
| P0L | ON (Northern) | 15 | 25 130 | 31.42 | 17.57 | 51.82 |
| P1H | ON (Northern) | 10 | 14 700 | 35.80 | 17.14 | 65.85 |
| P2A | ON (Northern) | 10 | 12 270 | 42.89 | 20.54 | 78.89 |
| P3B | ON (Northern) | 10 | 15 010 | 35.06 | 16.79 | 64.49 |
| P4N | ON (Northern) | 15 | 28 420 | 27.78 | 15.54 | 45.82 |
| P5A | ON (Northern) | 10 | 12 130 | 43.39 | 20.77 | 79.80 |
| P6A | ON (Northern) | 20 | 35 850 | 29.36 | 17.93 | 45.35 |
| P6B | ON (Northern) | 20 | 23 620 | 44.57 | 27.21 | 68.83 |
| R2L | MB | 10 | 14 680 | 35.85 | 17.16 | 65.94 |
| R2W | MB | 20 | 27 960 | 37.65 | 22.99 | 58.15 |
| R3J | MB | 15 | 27 220 | 29.00 | 16.22 | 47.84 |
| R7N | MB | 10 | 10 090 | 52.16 | 24.97 | 95.93 |
| S4P | SK | 10 | 12 480 | 42.17 | 20.19 | 77.56 |
| S6H | SK | 25 | 29 770 | 44.20 | 28.59 | 65.25 |
| T1A | AB | 20 | 26 160 | 40.24 | 24.57 | 62.15 |
| T5B | AB | 10 | 15 890 | 33.12 | 15.86 | 60.92 |
| T6A | AB | 10 | 14 710 | 35.78 | 17.13 | 65.80 |
| T6E | AB | 15 | 21 600 | 36.55 | 20.44 | 60.29 |
| V0H | BC | 25 | 50 980 | 25.81 | 16.70 | 38.10 |
| V0R | BC | 35 | 64 150 | 28.72 | 20.00 | 39.94 |
| V0X | BC | 15 | 19 960 | 39.55 | 22.12 | 65.24 |
| V1R | BC | 10 | 9950 | 52.90 | 25.32 | 97.28 |
| V1Y | BC | 25 | 31 970 | 41.16 | 26.63 | 60.76 |
| V2P | BC | 20 | 33 490 | 31.43 | 19.19 | 48.55 |
| V3M | BC | 20 | 34 410 | 30.59 | 18.68 | 47.25 |
| V5C | BC | 15 | 23 470 | 33.64 | 18.81 | 55.48 |
| V5H | BC | 20 | 32 850 | 32.04 | 19.56 | 49.49 |
| V5M | BC | 15 | 21 790 | 36.23 | 20.26 | 59.76 |
| V6A | BC | 20 | 16 530 | 63.68 | 38.88 | 98.35 |
| V7V | BC | 10 | 15 000 | 35.09 | 16.80 | 64.53 |
| V8L | BC | 15 | 22 190 | 35.58 | 19.90 | 58.68 |
| V8R | BC | 15 | 22 700 | 34.78 | 19.45 | 57.37 |
| V8X | BC | 15 | 22 420 | 35.21 | 19.69 | 58.08 |
| V9A | BC | 20 | 34 760 | 30.28 | 18.49 | 46.77 |
| V9N | BC | 15 | 27 450 | 28.76 | 16.09 | 47.44 |
| V9P | BC | 20 | 20 500 | 51.35 | 31.35 | 79.31 |
| V9R | BC | 20 | 25 050 | 42.02 | 25.66 | 64.90 |
| V9S | BC | 10 | 15 520 | 33.91 | 16.24 | 62.37 |
| V9W | BC | 20 | 27 620 | 38.11 | 23.27 | 58.86 |
Figure 4.
Esophageal squamous cell carcinoma incidence trends by FSA in Canada. Geographic maps illustrating incidence rates of esophageal squamous cell carcinoma (cases per million individuals per year) relative to the national average based on the Canadian Cancer Registry/Le Registre Québecois du Cancer databases. A, High incidence esophageal squamous cell carcinoma FSAs in British Columbia. This figure includes the highest incidence FSA, V6A in Vancouver, BC. B, High incidence esophageal squamous cell carcinoma FSAs in Quebec and New Brunswick. C, High incidence esophageal squamous cell carcinoma FSAs in Nova Scotia and PEI. D, High incidence esophageal squamous cell carcinoma FSAs in Newfoundland and Labrador province
4. DISCUSSION
To our best knowledge, no previous study performed has assessed the distribution of esophageal AC or SCC across the entire country and to this level of detail. In this work, we present important national trends corroborating those seen in similar studies from the United States, Europe, and Australia. At the national level, we report a steadily increasing overall burden of esophageal cancer in Canada, with a male predominance. Over 90% of these patients were > 60, reflecting a correlation between Canada's aging population and an increase in the current and projected incidence of cancer across the country.26 The average incidence rate was found to be 33.5 cases per million individuals per year, and the average age‐adjusted (to the World Standard Population) incidence rate was 23.0 cases per million individuals per year. This is consistent with worldwide trends:
Wong et al27 reported national age‐standardized incidence rates, standardized to the World Standard Population (in cases per million individuals per year) of 27 in Europe, 29 in North America, 34 in South America, and 29 in Australia. The authors additionally report an average male to female incidence ratio of 3:1,27 similar to our findings of 2.9:1.
Regarding the specific subtypes analyzed, we confirmed an important increase in esophageal AC incidence over time that has been seen in many developed countries. Age‐standardized esophageal AC incidence rates were reported by Thrift et al3 (in cases per million individuals per year) as 24.5 cases in Australia, 24.5 cases in the United States, and 13.9 cases in Sweden between 1999 and 2003. The proportion of obese Canadians has doubled between the 1980s and 2004.28 This potentially links esophageal AC to the higher rates of obesity seen in countries of a higher socioeconomic status.2, 3, 6, 29 With an aging population, patients may experience a longer duration of Gastroesophageal reflux disease (GERD) which would increase the risk of Barrett's esophagus and esophageal AC.30, 31 In addition, this increasing rate of esophageal AC may reflect the failure of screening appropriate patients or inadequate surveillance since Barrett's esophagus, GERD and obesity are potentially modifiable risk factors.32, 33
In the present study, we also described a decrease in esophageal SCC. The age‐standardized esophageal SCC incidence rates reported by Thrift et al3 (in cases per million individuals per year) corroborate our results: 25.1 in Australia, 18.1 in the United States, 14.0 in the Caucasian population of the United States, and 17.2 per in Sweden between 1999 and 2003. A study by Otterstatter et al29 reports an incidence of esophageal SCC in Canada of 13.5 cases per million individuals per year in 2004‐2006, reflecting the decreased incidence of esophageal SCC in recent years.29 A decline in tobacco smoking among Canadians may in part explain the decline in esophageal SCC incidence.34 SEER data during the period 1998‐2003 also corroborates these results; an overall incidence during that time was documented to be 18 cases per million individuals per year, slightly higher than the Canadian average.35 Esophageal SCC incidence in Europe tends to be much higher than in North America, likely due to much higher rates of cigarette consumption.
Geographic analysis of esophageal cancer trends throughout the country demonstrated that this malignancy localized more strongly to the Maritimes and BC. The present findings demonstrated clustering of esophageal AC cases in three particular areas of Canada; Vancouver Island, the coasts of the Great Lakes, and the coasts of the Northumberland Strait between NS and PEI. A recent study36 reported on clustering of esophageal cancer mortality in Caucasian men across the United States, which showed a high mortality from this cancer in the northeastern part of the country, particularly along the coasts of Lakes Michigan, Erie, and Ontario.36 Further analysis demonstrated high association of these areas with cigarette use, binge alcohol drinking habit, and obesity.36 This corroborates SEER data which reports that the highest incidence of esophageal AC is found in the Northeast and Midwest of the United States.35 In addition, although the heritable nature of esophageal cancer is not as strong as in some other cancers, familial clustering in high incidence areas has been observed in both esophageal cancer subtypes in previous studies.37, 38
The data in the present study demonstrate high incidence around several coastal cities of the Great Lakes, with the largest cluster surrounding Lake Ontario. The Great Lakes represent 80% of the fresh water supply in North America, providing drinking water for millions of people.39 A study by the Great Lakes Environmental Assessment and Mapping Project identified environmental stressors impacting this region, which may in part explain these findings.40 Their investigations revealed that Lakes Ontario, Erie, and Michigan scored highest on the cumulative stress index (CSI), due to being more populated and developed.40 Most common “stressors” ranged from toxins such as polychlorinated biphenyls and mercury, to pollution related to high shipping activity and charter, to land run‐off such as phosphorous and nitrogen.40 According to the World Wildlife Foundation's national assessment of Canada's freshwater, Vancouver Island, and parts of the NS and PEI were also highly affected by increased pollution related to industrial waste, urban runoff, and pipeline incidents.41 This accentuates the need to consider environmental exposures as an additional cardinal factor in the pathogenesis of this cancer among Canadians in these industrialized coastal regions.
Analysis of esophageal SCC trends, on the other hand, revealed high incidence in BC, rural eastern QC, and in the Maritimes. A recent report on tobacco use in Canada highlighted the overall decrease in smoking prevalence in the country, which may have contributed to the decrease of incidence of esophageal SCC.34, 42 The authors reported higher rates of cigarette consumption in NB, PEI, BC, AB, QC, and NL; these provinces happened to show higher incidence of esophageal SCC in the present study.42 Arnold et al identified a disproportionately high rate of esophageal SCC in central and southeast Asia.2 Similarly, BC has a large Southeast Asian population that may contribute to the higher incidence of esophageal SCC in that province.43
The highest incidence FSA corresponded to downtown Vancouver, specifically the DTES, colloquially referred to as Canada's “poorest postal code.”44 This low‐income area is known for unusually high rates of unemployment, crime, substance abuse, prostitution, and high incidence of infection with HIV/AIDS and hepatitis C virus.44 Efforts have recently been placed on providing better access to screening for certain cancers to which the DTES residents appear very vulnerable such as oral and cervical cancer.44, 45, 46 The possibility of high alcohol and tobacco use in this population, coupled with a lower access to education and healthcare, may make the residents of the DTES particularly vulnerable to esophageal SCC.
This study is not without limitations; in large retrospective studies using databases as those presently employed, there exists a risk of data omission or misclassification. While many other worldwide studies have noted the prevalence of esophageal adenocarcinoma to differ by ethnicity, data concerning ethnic background of Canadian patients was not collected by the CCR and LRQC databases and, hence, was not available for analysis.
It is also important to highlight that as Canada's healthcare system is a single‐tier (payer), which is funded and operated by the government, the data are collected with consistency, where each provincial and territorial cancer registry identifies tumors in its population by combining information from sources such as: cancer clinic files, radiotherapy and hematology reports, records from in‐patient hospital stays, out‐patient clinics, pathology and other laboratory/autopsy reports, radiology and screening program reports, medical billing and hospital discharge administrative databases. The CCR/LRQC performs multiple rigorous processes to ensure accuracy including an internal record linkage to identify possible duplicate records. These measures allow for high rates of detection and diagnostic accuracy of incidence data recorded by the registries.
Indeed, several studies investigated the detection rates and accuracy of diagnostic data in the largest provincial branch of the Canadian Cancer Registry: the Ontario Cancer Registry (OCR) which collects data from the most populous province. In fact, a case ascertainment of ~99%, a detection rate (detecting and accurately assigning index tumor site) of 81.4%‐96%, and a confirmation rate (correctly assigning tumor site) of 90.9% were documents by several studies,47, 48, 49 which confirms a high quality of data and detection rates in the examined registries.”
In conclusion, this epidemiologic study highlights areas of clustering of esophageal AC and SCC throughout Canada and provides an overview of known and potential risk factors to consider. Future analyses may confirm the existence of putative environmental risk factors presented in the present study. This report also provides the basis for locating and studying the areas of Canada that may benefit from more efforts for education and screening, as well as more focused distribution of healthcare resources in order to decrease incidence, morbidity, and mortality relating to esophageal cancer throughout the country.
CONFLICT OF INTEREST
Authors declare they have no conflict of interest regarding the content of this article.
AUTHOR CONTRIBUTIONS
Leila Cattelan collected and analyzed data and wrote the article. Feras M. Ghazawi analyzed data and co‐wrote the article. Michelle Le analyzed data. François Lagacé performed statistical analyses. Evgeny Savin performed statistical analyses. Andrei Zubarev performed statistical analyses. Jennifer Gantchev co‐wrote the paper. Marcel Tomaszewski co‐wrote the paper. Denis Sasseville collected data, designed and supervised the study, and co‐wrote the article. Kevin Waschke collected data, designed and supervised the study, and co‐wrote the article. Ivan V. Litvinov collected and analyzed the data, designed and supervised the study, and co‐wrote the article.
Supporting information
Cattelan L, Ghazawi FM, Le M, et al. Epidemiologic trends and geographic distribution of esophageal cancer in Canada: A national population‐based study. Cancer Med. 2020;9:401–417. 10.1002/cam4.2700
Funding information
This work was supported by the Cole Foundation Grant to Dr Litvinov, Canadian Dermatology Foundation research grants to Dr Litvinov and Fonds de recherche du Québec ‐ Santé (FRSQ# 34753 and 36769) research grants to Dr Litvinov. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Contributor Information
Kevin Waschke, Email: kevin.waschke@mcgill.ca.
Ivan V. Litvinov, Email: ivan.litvinov@mcgill.ca.
DATA AVAILABILITY STATEMENT
All original data is publicly available through Canadian Cancer Registry, Quebec Cancer Registry and Canadian Vital Statistics databases from Statistics Canada.
REFERENCES
- 1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359‐386. [DOI] [PubMed] [Google Scholar]
- 2. Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 2015;64:381‐387. [DOI] [PubMed] [Google Scholar]
- 3. Thrift AP, Whiteman DC. The incidence of esophageal adenocarcinoma continues to rise: analysis of period and birth cohort effects on recent trends. Ann Oncol. 2012;23:3155‐3162. [DOI] [PubMed] [Google Scholar]
- 4. Murphy G, McCormack V, Abedi‐Ardekani B, et al. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann Oncol. 2017;28:2086‐2093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Xie SH, Rabbani S, Petrick JL, Cook MB, Lagergren J. Racial and ethnic disparities in the incidence of esophageal cancer in the United States, 1992–2013. Am J Epidemiol. 2017;186:1341‐1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Rubenstein JH, Shaheen NJ. Epidemiology, diagnosis, and management of esophageal adenocarcinoma. Gastroenterology. 2015;149(302–317):e301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Souza RF, Krishnan K, Spechler SJ. Acid, bile, and CDX: the ABCs of making Barrett's metaplasia. Am J Physiol Gastrointest Liver Physiol. 2008;295:G211‐218. [DOI] [PubMed] [Google Scholar]
- 8. Rubenstein JH, Taylor JB. Meta‐analysis: the association of oesophageal adenocarcinoma with symptoms of gastro‐oesophageal reflux. Aliment Pharmacol Ther. 2010;32:1222‐1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Steevens J, Botterweck AA, Dirx MJ, van den Brandt PA, Schouten LJ. Trends in incidence of oesophageal and stomach cancer subtypes in Europe. Eur J Gastroenterol Hepatol. 2010;22:669‐678. [DOI] [PubMed] [Google Scholar]
- 10. Bashash M, Shah A, Hislop G, Brooks‐Wilson A, Le N, Bajdik C. Incidence and survival for gastric and esophageal cancer diagnosed in British Columbia, 1990 to 1999. Can J Gastroenterol. 2008;22:143‐148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Tinmouth J, Green J, Ko Y‐J, et al. A population‐based analysis of esophageal and gastric cardia adenocarcinomas in Ontario, Canada: incidence, risk factors, and regional variation. J Gastrointest Surg. 2011;15:782‐790. [DOI] [PubMed] [Google Scholar]
- 12. Parfitt JR, Miladinovic Z, Driman DK. Increasing incidence of adenocarcinoma of the gastroesophageal junction and distal stomach in Canada – an epidemiological study from 1964–2002. Can J Gastroenterol. 2006;20:271‐276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Amar L, Le M, Ghazawi FM, et al. Prevalence of human T cell lymphotropic virus 1 infection in Canada. Curr Oncol. 2019;26:e3‐e5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Ghazawi FM, Cyr J, Darwich R, et al. Cutaneous malignant melanoma incidence and mortality trends in Canada: a comprehensive population‐based study. J Am Acad Dermatol. 2019;80:448‐459. [DOI] [PubMed] [Google Scholar]
- 15. Ghazawi FM, Darwich R, Le M, et al. Uveal melanoma incidence trends in Canada: a national comprehensive population‐based study. Br J Ophthalmol. 2019. 10.1136/bjophthalmol-2018-312966. [DOI] [PubMed] [Google Scholar]
- 16. Ghazawi FM, Netchiporouk E, Rahme E, et al. Comprehensive analysis of cutaneous T‐cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy. Cancer. 2017;123:3550‐3567. [DOI] [PubMed] [Google Scholar]
- 17. Ghazawi FM, Netchiporouk E, Rahme E, et al. Distribution and clustering of cutaneous T‐cell lymphoma (CTCL) cases in Canada during 1992 to 2010. J Cutan Med Surg. 2018;22:154‐165. [DOI] [PubMed] [Google Scholar]
- 18. Darwich R, Ghazawi FM, Rahme E, et al. Retinoblastoma incidence trends in Canada: a national comprehensive population‐based study. J Pediatr Ophthalmol Strabismus. 2019;56:124‐130. [DOI] [PubMed] [Google Scholar]
- 19. Ghazawi FM, Darwich R, Le M, et al. Incidence trends of conjunctival malignant melanoma in Canada. Br J Ophthalmol. 2019. 10.1136/bjophthalmol-2019-313977. [DOI] [PubMed] [Google Scholar]
- 20. Ghazawi FM, Le M, Alghazawi N, et al. Trends in incidence of cutaneous malignant melanoma in Canada: 1992–2010 versus 2011–2015. J Am Acad Dermatol. 2019;80:1157‐1159. [DOI] [PubMed] [Google Scholar]
- 21. Ghazawi FM, Le M, Lagacé F, et al. Incidence, mortality, and spatiotemporal distribution of cutaneous malignant melanoma cases across Canada. J Cutan Med Surg. 2019;23:394‐412. [DOI] [PubMed] [Google Scholar]
- 22. Lagacé F, Ghazawi FM, Le M, et al. Analysis of incidence, mortality trends, and geographic distribution of breast cancer patients in Canada. Breast Cancer Res Treat. 2019;178(3):683‐691. [DOI] [PubMed] [Google Scholar]
- 23. Le M, Ghazawi FM, Alakel A, et al. Incidence and mortality trends and geographic patterns of follicular lymphoma in Canada. Curr Oncol. 2019;26:e473‐e481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Le M, Ghazawi FM, Rahme E, et al. Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada. Cancer. 2019;125(22):3953‐3959. [DOI] [PubMed] [Google Scholar]
- 25. Tsang M, Le M, Ghazawi FM, et al. Multiple myeloma epidemiology and patient geographic distribution in Canada: a population study. Cancer. 2019;125:2435‐2444. [DOI] [PubMed] [Google Scholar]
- 26. Xie L, Semenciw R, Mery L. Cancer incidence in Canada: trends and projections (1983–2032). Health Promot Chronic Dis Prev Can. 2015;35(Suppl 1):2‐186. [PubMed] [Google Scholar]
- 27. Malhotra GK, Yanala U, Ravipati A, Follet M, Vijayakumar M, Are C. Global trends in esophageal cancer. J Surg Oncol. 2017;115:564‐579. [DOI] [PubMed] [Google Scholar]
- 28. Shields M, Tjepkema M. Trends in adult obesity. Statistics Canada catalogue. Health Rep. 2006;17:53‐59. [PubMed] [Google Scholar]
- 29. Otterstatter MC, Brierley JD, De P, et al. Esophageal cancer in Canada: trends according to morphology and anatomical location. Can J Gastroenterol. 2012;26:723‐727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Fedorak RN, Veldhuyzen van Zanten S, Bridges R. Canadian Digestive Health Foundation Public Impact Series: gastroesophageal reflux disease in Canada: incidence, prevalence, and direct and indirect economic impact. Can J Gastroenterol. 2010;24:431‐434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Cook MB, Corley DA, Murray LJ, et al. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS ONE. 2014;9:e103508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Shaheen NJ, Falk GW, Iyer PG, Gerson LBACG. Clinical guideline: diagnosis and management of barrett's esophagus. Am J Gastroenterol. 2016;111(1):30‐50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014;63:7‐42. [DOI] [PubMed] [Google Scholar]
- 34. Janz T. Current smoking trends. Statistics Canada Catalogue Health Reports. 82–624‐X.
- 35. Trivers KF, Sabatino SA, Stewart SL. Trends in esophageal cancer incidence by histology, United States, 1998–2003. Int J Cancer. 2008;123:1422‐1428. [DOI] [PubMed] [Google Scholar]
- 36. Rubenstein JH, Morgenstern H, Longstreth K. Clustering of esophageal cancer among white men in the United States. Dis Esophagus. 2019;32:doy081 10.1093/dote/doy081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Chang‐Claude J, Becher H, Blettner M, Qiu S, Yang G, Wahrendorf J. Familial aggregation of oesophageal cancer in a high incidence area in China. Int J Epidemiol. 1997;26:1159‐1165. [DOI] [PubMed] [Google Scholar]
- 38. Chak A, Lee T, Kinnard MF, et al. Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. Gut. 2002;51:323‐328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Ward J, Mohapatra SP, Mitchell A. An overview of policies for managing polybrominated diphenyl ethers (PBDEs) in the Great Lakes basin. Environ Int. 2008;34:1148‐1156. [DOI] [PubMed] [Google Scholar]
- 40. Allan JD, McIntyre PB, Smith SDP, et al. Joint analysis of stressors and ecosystem services to enhance restoration effectiveness. Proc Natl Acad Sci USA. 2013;110:372‐377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Foundation WW . A national assessment of Canada's freshwater: Watershed Reports. WWF‐Canada: Watershed Reports; 2017:1‐24. [Google Scholar]
- 42. Reid JL, Hammond D, Rynard VL, Burkhalter R. Tobacco use in Canada: patterns and trends. Propel Centre for Population Health Impact: University of Waterloo; 2014. [Google Scholar]
- 43. Census Profile British Columbia . Statistics Canada. 2016.
- 44. Linden IA, Mar MY, Werker GR, Jang K, Krausz M. Research on a vulnerable neighborhood‐the vancouver downtown eastside from 2001 to 2011. J Urban Health. 2013;90:559‐573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Ogilvie G, Krajden M, Maginley J, et al. Feasibility of self‐collection of specimens for human papillomavirus testing in hard‐to‐reach women. CMAJ. 2007;177:480‐483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Poh CF, Hislop G, Currie B, et al. Oral cancer screening in a high‐risk underserved community–Vancouver Downtown Eastside. J Health Care Poor Underserved. 2007;18:767‐778. [DOI] [PubMed] [Google Scholar]
- 47. Greenberg ML, Barr RD, DiMonte B, McLaughlin E, Greenberg C. Childhood cancer registries in Ontario, Canada: lessons learned from a comparison of two registries. Int J Cancer. 2003;105:88‐91. [DOI] [PubMed] [Google Scholar]
- 48. Gupta S, Pole JD. The validity of pediatric cancer diagnoses in a population‐based general cancer registry in Ontario, Canada. BMC Cancer. 2016;16:885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49. Hall S, Schulze K, Groome P, Mackillop W, Holowaty E. Using cancer registry data for survival studies: the example of the Ontario Cancer Registry. J Clin Epidemiol. 2006;59:67‐76. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All original data is publicly available through Canadian Cancer Registry, Quebec Cancer Registry and Canadian Vital Statistics databases from Statistics Canada.