Prostate Cancer Incidence in Calabar - Nigeria

British Journal of Medicine & Medical Research 14(5): 1-10, 2016, Article no.BJMMR.23503 ISSN: 2231-0614, NLM ID: 101570965

SCIENCEDOMAIN international www.sciencedomain.org

Prostate Cancer Incidence in Calabar - Nigeria G. A. Ebughe1*, I. A. Ekanem1, O. E. Omoronyia2, M. A. Nnoli1, E. E. Ikpi3, and T. I. Ugbem1 1

Department of Pathology, University of Calabar, Nigeria. Department of Public Health, University of Calabar, Nigeria. 3 Department of Surgery, University of Calabar, Nigeria.

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Authors’ contributions This work was carried out by the urological cancer research team of the department of pathology University of Calabar collaboration with, urology surgery team and public health team all of University of Calabar and the Calabar cancer registry. Author GAE collated the data and wrote the work and author OEO analysed the results. Author IAE is the director of the Calabar cancer registry and provided the data, carried out the editing work. All the other co- authors provided the patients or pathology reports and read the manuscripts and effected corrections as well as approve the final manuscript. Article Information DOI: 10.9734/BJMMR/2016/23503 Editor(s): (1) Arun Kumar Nalla, College of Medicine, University of Illinois, Peoria, IL, USA. Reviewers: (1) Anthony Cemaluk C. Egbuonu, Michael Okpara University of Agriculture Umudike, Nigeria. (2) Anonymous, Erzincan University, Turkey. (3) Abrao Rapoport, Sao Paulo Unversity, Brazil. Complete Peer review History: http://sciencedomain.org/review-history/13691

rd

Original Research Article

Received 3 December 2015 Accepted 25th February 2016 th Published 14 March 2016

ABSTRACT Aim: The aim of this study is to determine the incidence of prostate cancer in men living in Calabar- Nigeria, which has not been determined up till now. Study Design: A trend analysis of prostate cancer cases in Calabar between 1st January 2004 to st 31 December 2013. Place and Duration of Study: Calabar cancer registry, May to June 2015. st Methodology: Record of prostate cancer cases in the Calabar cancer registry between 1 January st 2004 and 31 December 2013,was accessed. The patients age, sex, place domiciled in the last one year; whether rural or urban as well as prostate cancer topography and morphology were obtained and analyzed. The population of males domiciled in Calabar was determined using the 2006 national population census data and 3.0% population growth as specified by the national _____________________________________________________________________________________________________ *Corresponding author: E-mail: [email protected];

Ebughe et al.; BJMMR, 14(5): 1-10, 2016; Article no.BJMMR.23503

population commission. Excluded are all male genital tract cancers outside prostate cancer .The data was subjected to statistical analysis using SPSS version 21. Results: Two hundred and seventy nine (279) prostate cancer cases were seen, with mean (SD) age of subjects being 64.2 (9.5) years, with a range 40 to 95 years. About 249 cases (89.3%) occurred in those who are 55 years or older at time of diagnosis, with the commonest age group being 60-64 years. The age specific incidence of prostate cancer is 89 per 100,000, both crude and adjusted incidence rates were highest in 2012 (69.4 and 97.4 per 100,000, respectively). There was significant decrease in incidence rates in the initial five years (2004-2008), and increase in rates in the following five years of study (2009-2013). Within the 5-year period from 2004 to 2008, there was an average annual decrease in incidence rate of 9.63% (95% CI: 6.1%-12.8%). However, within the 5-year period from 2009 to 2013, there was an average annual increase in incidence rate of 11.95% (95%CI: 8.72% to 13.04%). Conclusion: This epidemiologic study demonstrate the incidence of prostate cancer in Calabar, Nigeria, with a predominance of patients in the 60- 64 years age group. West African states have to scale up population screening and study of this neoplasm.

Keywords: Calabar; prostate cancer; incidence; males. America, prostate cancer was noted to be the commonest cancer among males [23].

1. INTRODUCTION Nigeria is classified in the low incidence prostate cancer risk group although there is no country wide population based cancer registration, to enable a proper assessment [1,2]. GLOBOCAN 2012 estimates that prostate cancer is the commonest cancer in males, accounting for 11,944 cases per annum or 32% of male cancers. The Age Specific Incidence (ASR (w) is 30.7% using world standard population [2]. A time trend from the oldest population based registry in Ibadan with uninterrupted documentation since 1960 reveals that there has been a steady rise in prostate cancer incidence, with the result that by 1999 it became the dominant male cancer at 11% of all male cancers [3,4]. Hospital based data stretching over the six geopolitical zones of the country and over 19 cancer registries was aggregated in a collaborative effort in cancer registration, between Institute of human virology and Federal ministry of health. In that analysis of cancer data from these centres dating between January 2009 and December 2010, prostate cancer emerged as the commonest male cancer in the country [5]. Traditionally prostate cancer incidence is thought to be low in Sub-Saharan Africa [6-10], and curiously higher among Black American men, Black men in Britain and Black men in the Caribbean [11-15], all of African ancestry. Recent studies are painting a different picture, for example a report from Cameroon showed a high incidence rate comparable to those African American men and black men in the Caribbean [16], likewise other indigenous African studies now appear to be contradicting this [1,7,9,17-22]. In a recent study of Nigerian immigrants in

Data on age specific incidence rates (ASR) of prostate cancer in Africa are uncommon, more so in West Africa, due largely to issues of underdevelopment and lack of funding, which militate against proper cancer registration. To circumvent this obstacles novel approaches have been adopted by researchers sometimes, in a bid to trying to understand the magnitude of prostate cancer in their country. In one of such researches in Nigeria, Osegbe statistically determined the national annual prostate cancer burden to be, 110,000 cases with,20,000 mortality and the national prostate cancer risk to be 2%. This he achieved by prospectively examining a cohort presenting with prostate cancer symptoms in Lagos [24]. A limited Nigerian population based study in two registries in Abuja and Ibadan, covering 2.5% of the Nigerian population showed an ASR of prostate cancer of 25.8 per 100,000 and 17.4 per 100,000 [25] respectively. In a similar study in Abidjan cancer registry- Ivory Coast, Echimane et al. [26] found that prostate cancer was the commonest cancer in males with an ASR of 31.4 per 100,000. Going by these studies, the prostate cancer incidence in Nigeria and perhaps West Africa seem to be low, except that Angwofo, in Cameroon reported a high incidence comparable to those of black men in the Caribbean which is often reported to be very high [16]. A recent review in the United states, found that ASR of prostate cancer in Black American men ranged from 176 per 100,000 to 256/100,000 in some areas [13]. Equally black men presenting in a hospital in the US. with high Gleason score 2


prostate cancer tended to be originally from Jamaica, followed by West Africa before native black Americans [27]. High ASR for prostate is seen in black American men, but the highest reports are recorded in black men in the Caribbean, for example 304 per 100,000 in predominantly black men in Kingston Jamaica [28].

structure' which disturbs the sleep- wake cycle normally controlled by melatonin [38]. Several susceptibility genes have been implicated in prostate cancer aetiology; these range from genes that predict prostate cancer risk [39,40], to genes in the androgen pathways that increase susceptibility of men of African descent to prostate cancer [11,41]. Unlike breast cancer susceptibility genes (BRCA 1 & BRCA11) and other inherited cancers such novel susceptibility genes appear not to be found for prostate cancer as yet. Screening for prostate cancer using prostate specific antigen ( PSA) introduced in the 90's, and widely carried out in many developed countries has contributed in an upsurge in prostate cancer diagnosis [42-46], albeit accused of prompting over diagnosis at times [47-50]. In some studies researchers found no clear benefits on prostate cancer mortality [51]. Screening detectable cancer now accounts for sizable proportion of prostate cancer diagnosis in areas it is carried out [46,52]. Compared to developed areas, less developed areas like Nigeria demonstrate low prostate cancer awareness and screening tools per capita are few. Specialist in Radiology, Pathology and Urology services are few [4,23,53]. This may account for the fewer number of cases reported in this environment. Unpublished data from Calabar for example show that prostate cancer diagnosis more than trebled from 1999 when a foremost Urologist in Nigeria relocated to Calabar to strengthen the urology team.

Age group in years

The factors responsible for the prostate cancer disparity between black men of common ancestry living in Africa, America, Europe and the Caribbean is not known, so are aetiological factors for this disease [10]. Among the several factors which are beyond the scope of this study are environment, genetics and screening bias. Environmental factors are reported to be (biotic, abiotic and cultural) [6,7,29-31]. Increasing urbanization, western type diet are an important aspect of environment noted in prostate cancer aetiology [7,10,16,32,33]. In the last decade, the use of mobile phones have increasingly been linked to cancer. A combination radiofrequency waves emitted by cell phones as well as radio waves signals from base station have been reported in some studies to cause cancer [34,35]. Many other studies are inconclusive however [36,37]. More specifically a link has been made between exposure to artificial light at night to breast and prostate cancer incidence. It is thought that such exposure occasioned by night time use of computers, television and mobile devices distorts the 'circadian time >75 70-74 65-69 60-64 55-59 50-54 45-49 40-44 35-39 30-34 25-29 20-24 15-19 10--14 5--9 0--4 -

5,000

10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000 Population

Fig. 1. Male population of Calabar registry area (Calabar Municipality, Calabar-South and Akpabuyo), by age group, census of 2006 [54] 3


comparing the years (F=1.06, p=0.40; Fig. 1). There was non-uniformity in the annual distribution of cases seen within study period, with 2012 yielding the highest proportion of cases (45, 16.1%) (Table 2).

2. MATERIALS AND METHODS Data from the Calabar cancer registry stored in Canreg 4 format was accessed for prostate cancer patients in Calabar and Akpabuyo between January 2004 and December 2013 and transferred into SPSS version 21.0. Of interest is the date of incidence, age, place of residence, histological type of prostate cancer. All prostate cancer cases outside Calabar and Akpabuyo are excluded so are all non prostate cancers. The age distribution of the population of male resident in the study area was obtained from database of population census conducted in 2006, with intercensal estimations made in arrived at following the rules of the National Population Commission, Calabar, Nigeria (Fig. 1). World standard population was used to calculate the age-standardized or adjusted rates.

Table 1. Age-group distribution of prostate cancer subjects (N=279) Age group (years) 40-44 45-49 50-54 55-59 60-64 65-69 70-74 > 75 Total

Percentage 1.4 1.8 7.5 12.5 27.3 18.3 14.3 16.8 100.0

Table 2. Annual distribution of prostate cancer cases seen in Calabar (N=279)

3. RESULTS

Year 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Total

Data obtained from record of registered cases of prostate cancer seen within 2004 to 2013 from Calabar registry area, was entered and analyzed using SPSS version 21.0. Two hundred and seventy nine (279) cases were seen, with mean (SD) age of subjects of 64.2 (9.5) years, ranging from 40 to 95 years. About 249 cases (89.3%) were 55 years or older at time of diagnosis, with the commonest age group being 60-64 years (Table 1). There was no significant difference in the mean age at diagnosis of prostate cancer

Mean Age at Diagnosis in years

Frequency 4 5 21 35 76 51 40 47 279

Frequency 30 27 32 20 13 10 18 43 45 41 279

Percentage 10.8 9.7 11.5 7.2 4.7 3.6 6.5 15.4 16.1 14.7 100.0

70.0 69.0 68.0 67.0 66.0 65.0 64.0 63.0 62.0 61.0 60.0 59.0 58.0 57.0 56.0 55.0 2004

2005

2006

2007

2008 2009 Year

2010

2011

2012

2013

Fig. 2. Mean age at diagnosis of prostate cancer in Calabar, by year (2004-2013) 4


Both crude and adjusted incidence rates were highest in 2012 (69.4 and 97.4 per 100,000, respectively). There was significant decrease in incidence rates in the initial five years (20042008), and increase in rates in the following five years of study (2009-2013) (Table 3, Fig. 3).

89 per 100,000 is significantly higher than earlier reports of 25.8 and 19.1 per 100,000 posted for the cities of Abuja and Ibadan respectively [25], or 30.07% estimated by GLOBOCAN [2] all in Nigeria. This is equally higher than the value in many Asian countries, for example13.8 in Korea [55], 12.4 in Iran [56], and 24.9 in west Asian countries [57]. The rate is higher than those of some European countries, for example , 56.4 per 100,00 among white men in the United Kingdom [58], 74.7 in Latvia [59], and similar to some European countries. The rate is significantly less than that of Black American men [13] and black men in the Caribbean (304 per 100,000 ) and among British black men (166 per 100,000) [28,58]. To date less than 5% of the Nigerian population is covered by population based cancer registries, it is possible that

Within the 5-year period from 2004 to 2008, there was an average annual decrease in incidence rate of 9.63% (95% CI: 6.1%-12.8%). However, within the 5-year period from 2009 to 2013, there was an average annual increase in incidence rate of 11.95%% (95%CI: 8.72% to 13.04%).

4. DISCUSSION This research has shown that the incidence rate of prostate cancer is high in Calabar. An ASR of

Table 3. Annual crude, adjusted and age-specific incidence rates of prostate cancer in Calabar (2004-2013) Year 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Crude 47.4 42.5 50.3 31.3 20.3 15.6 27.9 66.5 69.4 63.0

Adjusted 68.4 63.7 73.1 46.8 29.9 24.2 38.2 92.4 97.4 94.6

40-44yr 5.7 0.0 0.0 5.7 0.0 0.0 0.0 5.6 5.6 0.0

45-49yr 6.9 0.0 0.0 6.8 0.0 0.0 6.8 6.7 6.7 0.0

50-54yr 17.6 17.5 117.5 0.0 17.4 8.7 17.3 51.7 17.2 8.6

55-59yr 102.5 34.1 101.9 33.9 67.5 33.7 16.8 16.7 83.4 99.8

60-64yr 109.8 127.7 127.3 127.0 18.1 18.0 71.9 215.1 303.7 231.6

65-69yr 185.0 221.3 220.7 183.4 73.1 109.4 36.3 290.0 216.8 324.2

70-74yr 203.7 243.6 242.9 40.4 80.5 40.1 158.7 119.7 159.1 317.2

>75yr 115.2 114.8 114.5 85.6 56.9 56.7 141.4 310.2 253.0 112.1

100.0 90.0 80.0

Age Std Rate

70.0 60.0 50.0 40.0 30.0 20.0 10.0 2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

0.0

Year Fig. 3. Trend in age-standardized incidence rate of prostate cancer in Calabar (2004-2013)

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prostate cancer incidence is grossly underestimated. According to World Health Organization, Nigeria has a low Physician to population ratio (0.4 per 1000 persons) (60] and the proportion of Urologist among the physicians is vanishingly small; equally the number of Pathologists to the population is small. If you combine these factors with lack of functional equipment in the health facilities, the general lack of expertise, non presentation of patients to the facilities due to ignorance, superstition and poverty, one can see how easy it is to underestimate the magnitude of the problem. Even in a small rural study in Nigeria Okoli et al. [61] demonstrated that the proportion of men with PSA ≥4 ng, ml was comparable to high risk prostate cancer population groups such as black American men [61]. They therefore suggested that larger population studies needed to be carried out in Nigeria to ascertain the magnitude of the prostate cancer problem.

72 years in Kingston Jamaica [28]. The ASR of prostate cancer in Calabar predictably increased from 2.3 per 100,000 in the 40 -44 years and peaked at 186 per 100,000 in the age group 65 69 years tailing off thereafter. Even though the results show that the highest number of cases 76 occurred in the 60-64 years age group, the highest yearly ASR of 324.2 per 100,000 occurred in the 65-69 age group followed by 317.2 per in the 70-75 age group. Equally the higher average ASR of 186 per 100,000, 161 per 100, 000 and 136 per 100,000 occurred in the age groups 60-69, 70-74 and ≥75 years in that order. This would suggest that prostate cancer in Calabar is a disease of the elderly, as is reported worldwide, what may account for the relatively young mean age of occurrence is the decreased life expectancy of our population. Were we to be living as long as populations in the developed world the average age of prostate cancer patient here would be similar to those patients in the advanced countries.

Within the 5-year period from 2009 to 2013, there was an average annual increase in incidence rate of 11.95%% (95%CI: 8.72% to 13.04%),in Calabar, this is in conformity with worldwide studies, conducted in low and high incidence prostate cancer zones [33,42,59,62-64]. Worldwide there is a gradual increase in prostate cancer incidence following the decline that was noticed in the 1990's [65]. In some countries like the United states pockets of incidence decreases now exist side by side with zones sill exhibiting increases; notable however even in such areas black men fare worse [13]. The great worry as GLOBOCAN observed is that even though the greater incidence is recorded in developed countries, the mortality is higher in the less developed countries of the world, where the incidence is low [66]. This is not a surprise going by the disparity of resources generally allocated to prevention, treatment and even palliation between these two populations [48,67,68]. In a world where as much as $76,000 could be spent on screening for prostate cancer on one patient, most of our patients in Calabar may not be able to afford $1 for the entire prostate cancer treatment.

This research appears to corroborate the direction of research thinking that the high incidence of prostate cancer among blacks in Diaspora may be due largely to people of West African ancestry. Folakemi Odedina et al. [72] carried out a comprehensive review of prostate cancer in West African countries and those connected to it by the trans Atlantic slave trade, concluded that in Ghana and Nigeria the burden of prostate cancer is high, even though publications in some West African countries in that review did not meet their standards [73]. That prostate cancer is a common disease among black men is no more in doubt. What is equally not in doubt is that the longer a man lives the higher the chance of him developing prostate cancer. In fact by age 100 years nearly 100 percent of the subjects will harbour latent prostate cancer. In wide review of Autopsy series, it was found out that 50% of Asian men had latent prostate cancer by age 90years;In Caucasians 50% of the men harbour the disease by age 80, while blacks achieve 50% by age 60 [42]. West Africa appears to be a hot bed for prostate cancer. Efforts, should be intensified in the areas early detection and treatment, to stem spate of late presentation with advanced stage disease and attendant high mortality that is often reported in this environment [74-77].

The Calabar prostate cancer patient is relatively young. The commonest age range affected by prostate cancer in Calabar is 60-64 years with the mean (SD) age of 64.2 (9.5) years. This is similar to the mean ages reported for Black American [69-71], Caribbean Black men [12] and British Black prostate cancer patients. This is lower than 68 years in Turkish patients as well as

5. CONCLUSION This epidemiologic study demonstrate the incidence of prostate cancer in Calabar, Nigeria 6


with a predominance of patients in the 60- 64 years age group. West African states have to scale up population screening and study of this neoplasm. This may reverse the gross underreporting of prostate cancer in this environment which seems to be the prevalent situation we have now.

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CONSENT It is not applicable.

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ETHICAL APPROVAL Approval for this study was granted by the Calabar cancer registry.

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ACKNOWLEDGEMENT The Calabar cancer registry is supported by a small grant from the International Agency for Research on Cancer (IARC), as well as support from the University of Calabar Teaching Hospital, both agencies deserve thanking for facilitating this work. Special thanks would also be paid to staff of the registry who meticulously entered the data and offered useful assistance in sorting the data. The study design and every other aspect of this work are however the brain child of the authors, and funding of the research is by the authors.

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COMPETING INTERESTS Authors have interests exist.

declared

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competing 13.

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