INCIDENCE AND MORTALITY RATE OF COLORECTAL CANCER IN MALAYSIA

INCIDENCE AND MORTALITY RATE OF COLORECTAL CANCER IN MALAYSIA AUTHORS: 1) Given name: Muhammad Radzi Family Name: Abu Hassan Affiliation: Gastroenterologist, Medical Department, Sultanah Bahiyah Hospital 2) Given name: Ibtisam Family Name: Ismail Affiliation: Research Officer, Clinical Research Centre, Sultanah Bahiyah Hospital 3) Given name: Mohd Azri Family name: Mohd Suan Affiliation: Medical Officer,Clinical Research Centre, Sultanah Bahiyah Hospital 4) Given name:faizah Family name:ahmad Affiliation: Research Officer, Clinical Research Centre, Sultanah Bahiyah Hospital 5) Given Name: Wan Khamizar Family name: Wan Khazim Affiliation: Colorectal Surgeon, Surgical Department, Sultanah Bahiyah Hospital 6) Given name: Zabedah Family name: Othman Affiliation: Oncologist, Department of Radiotherapy and Oncology,Hospital Kuala Lumpur, 7) Given name: Rosaida Family name: Mat Said Affiliation: Gastroenterologist, Medical Department, Hospital Ampang

8) Given name: Wei Leong Family name: Tan Affiliation: Medical Officer, Clinical Research Centre, Sultanah Bahiyah Hospital 9) Given name: Siti Rahmah@Noor Syahireen Family name: Mohammed Affiliation: Pharmacist, Clinical Research Centre, Sultanah Bahiyah Hospital 10) Given name: Shahrul Aiman Family name: Soelar Affiliation: Research Officer, Clinical Research Centre, Sultanah Bahiyah Hospital 11) Given Name:Nik Raihan Family name:nik Mustapha Address: Pathologist, Pathology Department, Sultanah Bahiyah Hospital Funding sources: Nil Corresponding author: Given name: Muhammad Radzi Family Name: Abu Hassan Address: Clinical Research Centre, Sultanah Bahiyah Hospital, KM 6,Jalan Langgar, 05460 Alor Setar, Kedah, Malaysia Phone number: +604-7406227 Fax number: +604-7407373 Email: drradzi91@yahoo.co.uk

ABSTRACT Objective:This is the first study in Malaysia that estimates the incidence and mortality rate for colorectal cancer(crc) patients by gender and ethnicities. Method:Utilising National Cancer Patient Registry-Colorectal Cancer (NCPR-CC) data where 4501 patients were selected, patients survival status was cross-checked with the National Registration Department. The analyses were performed with IBM SPSS Statistics. Age standardised rate(asr) is the proportion of colorectal cancer cases(incidence) and death(mortality) from 2008-2013, weighted by the age structure of the population from the Department of Statistics Malaysia and using WHO world standard population distribution. Result:Overall incidence rate for CRC was 21.3 cases per 100 000 population. CRC was highest among Chinese(27.4), as compared to Malay(18.95) and Indian(17.55).The ASR incidence rate of CRC was 1.33 times higher among male than female (24.16 and 18.14 cases per 100,000,respectively). 2011(44.7%) deaths were recorded. The overall ASR for mortality was 9.8 cases among Chinese (11.85), followed by Malay (9.56) and Indian (7.08). The ASR for mortality was about 1.42 times higher among male(11.46) compared to female(8.05) Conclusion: CRC incidence and mortality is higher in male compared to female. Chinese ethnicity has the highest incidence of CRC followed by Malay and Indian. The same trend was observed for the mortality ASR rate. Keywords: Colorectal Cancer, Incidence, Mortality, Ethnicity, Gender, Malaysia

INTRODUCTION Colorectal cancer (CRC) has become the third most common cancer globally [1] and it has been considered as one of the leading causes of death particularly in Western countries [2]. In 2014, it was reported that 136 830 individuals were projected to be newly diagnosed colorectal cancer patients with 50 310 mortality projection in United States alone [3]. Asian countries are not excluded from the rise in CRC for the past 20 years [4] and the disease has also become a major health concern. In Malaysia, CRC was found to be the second most common cancer, based on National Cancer Registry Report 2007 [5]. Several studies had been conducted in Asian countries such as Japan, Hong Kong and Singapore to investigate the incidence of CRC. In a study done by Tamara et al, it has been reported that there was an increase in incidence among Japanese particularly in male compared to female in all of its cohorts [6]. Similarly, an increase in incidence of CRC was observed from 1983 until 2006 in Hong Kong [7]. Different ethnicity background has also been postulated to influence the risk of CRC. Mateka et al studied the trend in incidence and mortality rates of CRC in the USA found that that it was higher among Black American (66.9 per 10000 population) compared to White American, Asian, Hispanic and Indian [8]. Located at the heart of South East Asia, Malaysia is a country with diverging ethnic groups and cultural system. With more than 26 million population [9], Malaysia is a unique country which comprised of three major ethnicities i.e Malay, Chinese and Indian that become our focus in this study. To our knowledge, this is the first study in Malaysia that estimates the incidence and mortality rate for CRC patients by gender and ethnicities.

METHODOLOGY This study utilised secondary data from the National Cancer Patient Registry-Colorectal Cancer (NCPR-CC). NCPR-CC is a national clinical database which aims to systematically collect data on important aspects of colorectal cancer relevant to its prevention and treatment to enable healthcare planning, implementation and evaluation in a defined population in Malaysia. Source Data Providers (SDP) represent different regions of Malaysia i.e. the peninsular (north, central, south and east coast), as well as, east Malaysia (Sabah and Sarawak). In our study, there were 34 participating centres with at least one representative hospital from each 14 states of Malaysia. These SDP comprised mainly of major referral public hospitals treating colorectal cancer. Clinical Research Centre, Hospital Sultanah Bahiyah is the coordinating centre that manages the registry. All colorectal cancer cases diagnosed from January 2008 until December 2013 were included. All data are stored in a secure database with restricted access to authorised persons only. For the purpose of this study, database of the registry was locked on 30 April 2014. This study utilised data from 34 participating centres that were entered until 30 April 2014. Initially, 7287 data were captured. Following data cleaning (namely exclusion of duplicated entry, anal cancers and metastatic lesions to the colorectum), a total of 4501 patients were identified and included in this study. Patients survival status was confirmed through checking their medical records, as well as, with the National Registration Department, Ministry of Home Affairs. This study was registered with National Medical Research Registry and approved by Medical Research Ethical Committee (NMRR-07-49-242). Data analyses were performed using IBM SPSS Statistics for Window software version 20.0 [10]. Descriptive statistics were utilized to present the frequency and percentage for age groups, gender, ethnicity, primary cancer site and patient status. Cross tabulation was used to get the number of age category among gender and ethnic by patient status. Results of cross tabulation were copied and pasted into Microsoft Excels 2007 to calculate the age standardised rate (ASR). Age standardised rate (ASR) was needed to compare the cancer incidence and mortality with adjusted age-specific between the different gender and ethnic in Malaysia, as well as, international comparisons. Age standardised rate (ASR) is defined as the rate of colorectal cancer cases (incidence) and death (mortality) per 100,000 population with a standard age structure. Age standardised rate (ASR) was calculated by the direct approach given by the following equation:

ASR = r i ( n is n is ) where r i is the weight from the WHO world standard population in the ith age class [11] and n is is the weight from the ith age class of the population from the Department of Statistics (DOS) [9], Malaysia.

RESULTS There were 4501 cases of colorectal cancer reported in the National Cancer Patient Registry- Colorectal Cancer (NCPR-CC) within the period of 2008-2013. Table I showed that out of 4501, 55.9% were male and 42.9% were female (Table I). In term of ethnicity, Malay ethnic was the majority (42.7%) followed by Chinese (40.3) and Indian (5.8%). Table II shows that the age standardised incidence rate of colorectal cancer per 100,000 populations was highest among Chinese (27.4) as compared to Malay and Indian (18.95 and 17.55 cases per 100 000 respectively). In addition, the age standardised incidence rate of colorectal cancer was about 1.33 times higher among male than female (24.16 and 18.14 cases per 100,000 respectively. There were 2011 (44.7%) deaths recorded out of 4501 colorectal cancer patients during the six years period (Table I). The mortality rate per 100,000 population was also highest among Chinese (11.85), followed by Malay (9.56) and Indian (7.08). The age standardised mortality rate of colorectal cancer was about 1.42 times higher among male compared to female (11.46 and 8.05 cases per 100,000 respectively).

DISCUSSION As a multiethnic country, it is of our interest to study the incidence and mortality rate of CRC in Malaysian population particularly amongst the three main ethnicities i.e Malays, Chinese, and Indians. The result showed that the overall age standardised incidence rate for colorectal cancer in Malaysia was highest amongst Chinese (27.35 per 100 000 populations), followed by Malay and Indian (18.95 and 17.55 per 100 000 populations, respectively). Similar finding was reported from population-based Singapore cancer registry report (2008-2012). In their report, age standardised incidence rate for CRC Chinese ethnicity was 35.1 per 100 000 population, as compared to Malay and Indian ( 24.6 and 17.1 per 100 000 population, respectively) [12]. Our study also compared the incidence of CRC between male and female. The age standardised incidence of CRC is 1.33 times higher in male than female (24.2 and 18.1 cases per 100,000 respectively). Despite of geographical variation, similar finding was observed worldwide. Incidence rate was found to vary ten-fold in male and female where the highest estimated rate of CRC being in Australia/New Zealand with 44.8 and 32.2 per 100 000 populations in male and female, respectively. The same scenario was observed in Western Africa with male (4.5 per 100 000 population) compared to female with ( 3.8 per 100 000 population) [1]. There were 2011 (44.7%) deaths out of 4501 colorectal cancer patients recorded during the six-year period. The mortality rate per 100,000 population, it mirrors the trend in CRC incidence, in which Chinese ethnicity had the highest mortality (11.9), followed by Malay (9.6) and Indian (7.1). Meanwhile, age standardised mortality rate in male was 1.42 times higher than female (11.46 and 8.05 per 100 000, respectively). A study by Jemal et al on global cancer statistics showed that developed nations had age standardised mortality rate of 15.1 per 100,000. As for South East Asia, age standardised mortality rate was 15.2 per 100,000 for male and 12.9 per 100,000 for female [13]. Based on the report from GLOBOCAN project, it was demonstrated that in the South East Asia Region, the overall incidence of CRC in Malaysia was the third highest (18.3 per 100 000 population) when compared with other country particularly its neighbouring country such as Singapore (33.7 per 100 000 population), Brunei (250.0 per 100 000 population), Phillipines (13.1 per 100 000 population), Indonesia (12.8 per 100 000 population) and Thailand (12.4 per 100 000 population). As for the mortality rate, Brunei exhibited the highest mortality rate (12.0 per 100 000 population) followed by Singapore, Malaysia, Indonesia, Philipines and Thailand (11.8,9.4,8.6,7.8, and 7.3 per 100 000 population, respectively) [1].

According to Parkin (2009), it is important for a registry database to review their data completeness index where only a high degree of completeness will ensure the incidence and survival rate are close to their true value [14, 15]. It was suggested that one of the possible ways to report the overall data completeness of the registry is by calculating the mortality per incidence (M: I) ratio. In our dataset, we demonstrated the index of completeness by assessing the M:I ratio, where we compared the number of deaths, which were obtained from National Registration Department, Ministry of Home Affairs, a source independent of the registry against the number of cases reported for the period of time (2008-2013). To our knowledge, this study is the most representative data reported so far which investigated the incidence and mortality of CRC in different ethnicities in Malaysia, comparing between males and females. In our study, out of 34 centres that contributed to the data, there was at least one representative hospital from each 14 states of Malaysia where most of the centres are the major referral public hospitals treating colorectal cancer. In conclusion, we have demonstrated that the overall incidence of CRC in Malaysia was 21.3 cases per 100 000 population where it was highest amongst Chinese ethnicity compared to Malay and Indian. Similarly, Chinese ethnicity showed the highest mortality rate compared to other ethnicity. Incidence and mortality rate were both higher in males as compared to females. These findings illustrate the overall incidence and mortality rate of CRC in Malaysia as well as highlighting the differences between different ethnicity and gender. It is our hope that these findings will help the policy maker to strategies and improve CRC disease control plan in Malaysia. ACKNOWLEDGEMENTS The authors would like thank Director General of Health Malaysia for permission to publish this paper. The authors would also like to thank all participating centres that contribute to the successful of this registry. CONFLICT OF INTEREST The authors have no conflicts of interest to declare for this study.

References: 1. International Agency for Research on Cancer, GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Available from : http://globocan.iarc.fr/default.aspx. 2.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. 3.Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29. 4.Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev 2009;18:1688-1694. 5.Zainal Ariffin O, Nor Saleha I. National cancer registry report: Malaysia cancer statistics-data and figure 2007. Putrajaya, Ministry of Health Malaysia 2011 6.Tamura K, Ishiguro S, Munakata A, Yoshida Y, Nakaji S, Sugawara K. Annual changes in colorectal carcinoma incidence in Japan. Analysis of survey data on incidence in Aomori Prefecture. Cancer 1996;78:1187-1194. 7.Yee YK, Gu Q, Hung I, Tan VP, Chan P, Hsu A, et al. Trend of colorectal cancer in Hong Kong: 1983-2006. J Gastroenterol Hepatol 2010;25:923-927. 8.B Iliou C. Interesting Trends In Incidence and Mortality Rates of Colorectal Cancer in the United States of America. Journal of Gastrointestinal & Digestive System 2011 9.Malaysia JP. Taburan Penduduk Dan Ciri-Ciri Asas Demografi 2010: Putrajaya: Jabatan Perangkaan Malaysia 2010; 2010 10.SPSS I. IBM SPSS statistics for Windows, version 20.0. New York: IBM Corp Available from: 11.Ahmad OB B-PC, Lopez AD, Murray CJ, Lozano R, Inoue M. Age standardization of rates: a new WHO standard. 2001 12.Peng L, Ling C, Yew C, Aizen J, Yun L, Ho W. Singapore Cancer Registry Interim Annual Registry Report Trends in Cancer Incidence in Singapore 2008-2012. National Registry of Diseases Office (NRDO) 2012 13.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. 14.Bray F, Parkin DM. Evaluation of data quality in the cancer registry: principles and methods. Part I: comparability, validity and timeliness. Eur J Cancer 2009;45:747-755. 15.Parkin DM, Bray F. Evaluation of data quality in the cancer registry: principles and methods Part II. Completeness. Eur J Cancer 2009;45:756-764.

Table I. Descriptive statistics of colorectal cancer cases in National Cancer Patient Registry-Colorectal Cancer, Malaysia, 2008-2013 Variables n (%) Age Groups <19years 11 (0.2) 20-24years 17 (0.4) 25-29years 47 (1.0) 30-34years 65 (1.4) 35-39years 112 (2.5) 40-44years 194 (4.3) 45-49years 328 (7.3) 50-54years 465 (10.3) 55-59years 627 (13.9) 60-64years 713 (15.8) 65-69years 650 (14.4) 70-74years 616 (13.7) >75years 613 (13.6) Not reported 43 (1.0) Gender Male 2518 (55.9) Female 1933 (42.9) Not reported 50 (1.1) Ethnic Malay 1922 (42.7) Chinese 1814 (40.3) Indian 259 (5.8) Others 484 (10.8) Not reported 22 (0.5) Primary Cancer Site Left sided 3480 (77.3) Right sided 770 (17.1) Not reported 251 (5.6) Patient Status Alive 2490 (55.3) Dead 2011 (44.7)

Table II. The incidence and mortality of patients in the NCPR-Colorectal Cancer, 2008-2013 Incidence Mortality Mortality/Incidence Ratio Characteristics Overall Male Female Overall Male Female Overall Male Female Overall 21.32 24.16 18.14 9.79 11.46 8.05 0.46 0.47 0.44 Ethnic Malay 18.95 21.79 16.09 9.56 11.56 7.57 0.50 0.53 0.47 Chinese 27.35 30.77 23.22 11.85 13.47 10.07 0.43 0.44 0.43 Indian 17.55 21.43 13.71 7.08 9.63 4.78 0.40 0.45 0.35