Trends in the Incidence and Mortality of Colorectal Cancer in a Brazilian City

doi:10.21203/rs.3.rs-94961/v1

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Trends in the Incidence and Mortality of Colorectal Cancer in a Brazilian City

https://doi.org/10.21203/rs.3.rs-94961/v1

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published 09 Dec, 2020

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Objectives: This study was conducted to analyse the trends in the incidence and mortality of colorectal cancer (CRC) in the city of Aracaju, Sergipe State, Brazil, between 1996 and 2015 through statistical analysis using the Joinpoint Regression Program 4.7.0.0. and to identify its geographical distribution in the municipality.

Results: A total of 1,322 cases and 467 deaths of CRC over the study period were included. Men´s incident cases comprised 40% of the sample, and women´s 60%. The death cases were 43% for men and 57% for women. Among the 20 – 44 year age group, for males, there was a highest significant growth trend. For women, the growth trend, with the Annual Percent Change (APC) observed, was the 45 and 64 years age group. Regarding mortality both genders, trends were stable. Regarding geographic distribution, there was a constancy of hotpoints in the northeast region of the municipality. This study showed the increasing in incidence mainly the young men between 20 to 44 years, with significantly statistical, but with mortality stability in Aracaju.

Cancer Biology

Health Policy

Colorectal cancer

Demography

Incidence

Mortality

The epidemiological transition occurring throughout the world and in Brazil has drawn the attention of the health care field towards non-communicable chronic diseases (NCDs) (1). Cardiovascular diseases, respiratory diseases, diabetes and its complications and cancer are pathologies that contribute to the increased incidence and mortality of NCDs.

The incidence and mortality of colorectal cancer (CRC) has increased in several regions of the world (2). In the United States, in 2018, it was the fourth most common type of cancer diagnosed in both sexes (3, 4). In Brazil, estimates calculated by the José de Alencar Gomes da Silva National Cancer Institute (INCA) for the 2020–2022 triennium show that, when non-melanoma tumours are excluded, CRC will rank between second and fourth for men and between second and third for women depending on the studied region (5).

Given its features, such as the high possibility of prevention via screening through examinations and the good chance of cure if diagnosed in early stages, a study of the trends of incidence and mortality of CRC in the city of Aracaju, Northeast Brazil, is essential. Assessments such as topographic distribution, proportions of histological subtypes, mortality/incidence ratio and the spatial distribution of this disease are also extremely valuable for understanding and decision-making for epidemiological control.

The present study is a partially ecological study of time series aggregates divided into three parts: descriptive analysis, trend analysis and geoprocessing.

The inclusion criteria were men and women who were diagnosed with and/or died of CRC from 1996 to 2015 and were registered in the Population-Based Cancer Registry (RCBP) and/or in the Mortality Information Service (SIM) under the following International Classification of Diseases in Oncology, 2nd and 3rd edition codes: C18 to C20. Regarding morphology, the codes were 80003, 80103, 80203, 80513, 80703, 80723, 81233, 81243, 81403, 82013, 82103, 82113, 82203, 82403, 82463, 82603, 82613, 82623, 82633, 84803, 84813, 84903, 85603, 88003, 89363, 95903, 95913, 96823, 96873, 96923, 96983, 96993, 97153. These data were collected according to the International Agency for Research on Cancer (IARC) standards (6, 7) and are validated in Brazil by the INCA.

For the descriptive analysis, the following data were calculated for each sex and for both sexes combined: proportions of incident cases and death, proportions of histological types, topographic distribution of the disease in the colon and the mortality/incidence ratio (8). To calculate the rates, the half-period population for each age group provided by the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística – IBGE) (9) was used as the basis, along with age standardization to the world population (10).

The incidence and mortality trends were calculated using the Joinpoint Regression Program 4.7.0.0, which identifies annual percent changes (APC) and their averages (AAPCs) over a studied period. The software calculates the trends, starting with the minimum joinpoint of 0, and tests the statistical significance (Monte Carlo test) of the changes by adding more joinpoints (8). To examine mortality trends, the age groups of 45 to 64 years, older than 65 years and all ages were selected, given that the incidence and, consequently, mortality are much lower among younger individuals and that several years had no cases of death in younger age groups, making it impossible to calculate trends.

The spatial distribution of CRC incidence density was mapped using the heat map function (kernel function) of the Geographic Information System (GIS) multiplatform software QGis 2.18.0 (11). Address coordinates were collected by the RCBP, and inconsistent addresses were individually evaluated and obtained using Google Maps.

Between 1996 and 2015, 1322 cases of CRC were registered in the RCBP, with 40.5% corresponding to males and 59.5% to females. The SIM, in turn, recorded 467 deaths in the same period, 42.6% of which corresponded to males and 57.4% to females (Table 1). Regarding the topographic distribution of the neoplasia, for both sexes, the left colon and rectum were the most common sites (Table 1). Among the histological subtypes, adenocarcinoma prevailed (Table 1).

Table 1

Incident cases and deaths proportions, mortality/incidence ration, topographic distribution and proportion of histological subtypes.
	Male	Female
Total cases Death cases Incident and mortality proportion	535 199 40.5;42.6%	787 268 59.5;57.4%
Topographic distribution
Right	12.5%	13.72%
Transverse	2.99%	3.43%
Left	28.4%	28%
Colon (not specified)	24.11%	21.98%
Overlapping*	4.48%	1.9%
Rectum	25.79%	28%
Appendix	1.68%	2.79%
Histological subtypes
Adenocarcinoma	95%	93.69%
Lymphoma	0.93%	0.76%
N. endocrine	3.17%	5.2%
Sarcoma	0.37%	0.38%
*Overlapping injuries

The analysis of the incidence showed constant growth for both sexes, however the mortality trends in all age groups was stable. In terms of incidence, the highest APC was observed for women between 45 to 64 years, with an APC of 2.3 (95% CI 0.4–4.2). For men, the highest APC of 7.2 (95% CI 3.7–10.8) was related to the age group of 20 to 44 years.

When analysing the mortality trends for women and man in the age groups studied (45 to 64, + 65 years and all ages), the findings were not statistically significant.

Through the analysis of the Kernel Map, it was divided in three periods and other map with all the time of the study (1996/2002; 2003/2009; 2010/2015 and 1996/2015). In the first period, the areas with the highest density corresponded the central and northeast regions followed by a small scattered points in the north and central-south regions. When compared to the second period, there was a maintenance density in the northeast of the municipality, with an increase in the central region. In the third analysis period, it was observed the maintenance the highest density in the northeast region, similar to the second study period.

When the incidence trends were evaluated by age groups based on life stages (0–19, 20–44, 45–64 and + 65 years), there was stable and constant increase in incidence for both females and males. For women, the APCs varied very little. For men, the highest APC was observe among the youngest group (20 to 44 years). As it is a pathology with a multifactorial origin, factors such as increase of weight secondary to changes in dietary patterns and sedentary lifestyle may be contributing to this increase(12). In countries with a very high human development index (HDI), such as the United States, a decrease in the incidence rates of CRC among individuals older than 50 years is being observed, but other groups are showing increasing and constant APCs of 2.7 (< 40 years) and 1.7 (40 to 49 years) (13). The decrease among individuals over 50 years is most likely due to public health policies (13). Because CRC is largely preventable, screenings reduce the incidence among the elderly; however, as screening is performed earlier, the incidence in the younger population increases(14).

Regarding mortality, there was a stability regarding the trends for men and women over 65 years, between 45 and 64 years and all ages. The literature has shown for regions with an HDI similar of Brazil, the incidence and mortality trends of CRC have been increasing(15). This reflects the difficulty of access to healthcare, with consequent advanced stages at diagnosis (16, 17), in addition to poor infrastructure, lack of adequate screening and treatment (18), and age-related comorbidities (19).

During the studied period, there was a higher proportion of incident and death cases among women than men (59.5% x 40.5% and 57.4 × 42.6%, respectively). This finding differentiates the reality of the studied population from the results obtained by Ansa et al. (13), who evaluated data from the Surveillance, Epidemiology, and End Results (SEER) Program and observed that CRC was more prevalent among men from 2000 to 2014 in the United States. This difference occur because of the different proportions between men/women in the two regions of study (20, 21). In the state of Sergipe, referring to the 2010 census, for older than 40 years, the male:female ratio was 1:1.16, while in the United States this same ratio for the period was 1:1.09 (20, 21).

When the adjusted incidence rates were analysed, we observed that for the female and male sex, there was a similar, however intermediary variation in the adjusted rate for the world population. These intermediate values occurred due to the epidemiological transition observed in countries with a lower HDI. The highest incidence rates are concentrated in regions with higher HDI, for example, Australia and New Zealand (36.7 cases per 100,000), Europe (28.8–32.1 cases per 100,000), East Asia (26.5 cases per 100,000) and North America (26.2 cases per 100,000) (22). In regions with lower HDI, such as Africa and South-Central Asia, there are lower incidence rates (6.4–9.2 per 100,000 and 4.9 per 100,000, respectively) (22).

For both sexes, the left colon and rectum were the most common sites of CCR (Table 1). The epidemiological relevance of these data results from the fact the most common sites are accessed by flexible rectosigmoidoscopy, which may be a less expensive and more effective screening measure for economically and socially less-developed countries. Ahnen et al. (23) observed a higher prevalence of CRC in the left colon and rectum in the US in 2014, especially among younger individuals.

When the histological subtypes of CRC were considered, approximately 94.5% of the CRCs were adenocarcinoma for both sexes. These values are similar to those described in the international and American literature, in which more than 90% of CRCs are adenocarcinomas (24).

The Kernel Map showed a distribution of the hotpoints in the northeastern region. This result may have accurred due the higher population densities, referring to the 2010 census, located in this region (25). When analyzing the hotpoints taking into account the 2000 census, there was a small change in the population density (25). When assessing the monthly household income distributed bu neighborhood using the 2000 census data as a reference, it is observed that the neighborhoods with the highest monthly household in come values are included in the hotpoints of the entire period studied (1996–2015) (25, 26).This corroborates the relationship between a higher HDI and a higher incidence (27). The neighborhoods with the lowest monthly incomes are also found in the hotpoint areas due to their proximity to the more affluent areas and, mainly, due to their population density.

The strengths of our study was: a long serie times (1996–2015); incidence data validated nationally and internationally with the data base quality showing a diagnose with microscopic verification 94.8%; the death certificate only cases 3.5% and C80 1.6%.

The incidence rates of CRC have been increasing steadily in the municipality of Aracaju are compatible with those of regions with similar HDIs. The APC among young men is noteworthy, showing that CRC has been following an ascending evolution already noted in countries with higher HDIs. Regarding mortality, there was a stability to all genders. Regarding topography, the left colon and the rectum were the most common, with adenocarcima being the most common histological subtype. Our findings indicate that public health measures are necessary. Exams such as flexible rectosigmoidoscopy every 5 years and annual faecal occult blood tests are relatively inexpensive and, according to the literature, will reduce the rates of the third most common malignant neoplasia worldwide.

The limitations were the difficult to get the geographic coordinates, mainly in the oldest years. However, the loss of the data were 7%. For mortality calculations, the collected data were released by SIM. It is known that the filling in of death certificates depends on the declarant, wich can damage the conclusions, underestimating the results. However, the data we have are official. Improvements in filling out death certificates, regarding cancer, are occurring and are indispensable for their correct monitoring (28).

APC: Annual Percent Change

AAPC: Annual average percentage change

CAAE: Certificate of Presentation of Ethical Appreciation

GIS: Geographic Information System

HDI: Human Development Index

IARC: International Agency for Research on Cancer

INCA: Cancer national institute

CRC: colorectal cancer

RCBP: Population-Based Cancer Registry

SIM: Mortality Information Service

UFS: Federal University of Sergipe

Ethics approval and consent to participate

This study was submitted and approved by the Research and Ethics Committee of Federal University of Sergipe (Universidade Federal de Sergipe – UFS), and registered under CAAE number 15415819.8.0000.5546. We state that all methods were accomplished in accordance with the relevant guidelines and regulations. To warrant confidentiality, we employed unidentified databases, for which it would have not been feasible to obtain informed consent. Therefore, we requested the Ethics Committee for exemption, which was granted, all in conformity with Resolution 466 of December 2012 of the Ministry of Health, Brazil.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request

Funding

There was no funding

Acknowledgements

The authors would like to thank the Cancer Registry and the Mortality System Information (José Erinaldo Lobo de Oliveira, Elma Santana de Oliveira, Maria das Graças Prata França, Sueli Pina Vieira, Marina Kobilsek, Maria Cristina Conceição Coelho Santos, Maria das Graças Rodrigues de Melo, and Cecília Ferreira) for the hard work of collecting data in a safe way to carry out this paper.

Consent for publication

Not applicable

Competing interests

This research was conducted with the partial support of a Research Development Grant from the Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SE to C.A.L. The authors declare no other competing interests.

Authors' contributions

Conception and design: A.R.M. and C.A.L.; analysis and interpretation of data: A.R.M., C.A.L., M.S.L., M.R.S., M.O.S. and A.D.M.; drafting of the article: A.R.M., E.A.C.B., H.F.F.S., A.D.M., A.C.R.L., M.A.P.N. and M.S.D.; critical revision of the article: M.O.S., C.A.L., A.M.S. and E.A.C.B.; final approval of the article: C.A.L., A.M.S., M.A.P.N. and M.O.S..

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Adjusted incidence and mortality in adenocarcinoma rates for both sexes per 100,000.

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Trends in the Incidence and Mortality of Colorectal Cancer in a Brazilian City

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Authors' contributions

References

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