Worldwide Variations in Colorectal Cancer^†‡

Abstract

Previous studies have documented significant international variations in colorectal cancer rates. However, these studies were limited because they were based on old data or examined only incidence or mortality data. In this article, the colorectal cancer burden and patterns worldwide are described using the most recently updated cancer incidence and mortality data available from the International Agency for Research on Cancer (IARC). The authors provide 5-year (1998–2002), age-standardized colorectal cancer incidence rates for select cancer registries in IARC's Cancer Incidence in Five Continents, and trends in age-standardized death rates by single calendar year for select countries in the World Health Organization mortality database. In addition, available information regarding worldwide colorectal cancer screening initiatives are presented. The highest colorectal cancer incidence rates in 1998–2002 were observed in registries from North America, Oceania, and Europe, including Eastern European countries. These high rates are most likely the result of increases in risk factors associated with “Westernization,” such as obesity and physical inactivity. In contrast, the lowest colorectal cancer incidence rates were observed from registries in Asia, Africa, and South America. Colorectal cancer mortality rates have declined in many longstanding as well as newly economically developed countries; however, they continue to increase in some low-resource countries of South America and Eastern Europe. Various screening options for colorectal cancer are available and further international consideration of targeted screening programs and/or recommendations could help alleviate the burden of colorectal cancer worldwide. CA Cancer J Clin 2009;59:366–378. © 2009 American Cancer Society, Inc.

Introduction

Colorectal cancer is the fourth most common cancer in men and the third most common cancer in women worldwide,1 and significant international variations in the distribution of colorectal cancer have been observed.2, 3 Risk factors for colorectal cancer include obesity, a diet low in fruits and vegetables, physical inactivity, and smoking,4-6 and as such it was once a disease primarily observed in longstanding developed nations whose populations typically exhibit these factors.7 However, in recent years, high colorectal cancer rates have been reported in newly developed countries around the globe in which the risk was once low.1, 8 The goals of this article are to describe global colorectal cancer incidence and mortality patterns using the most recent data available from the International Agency for Research on Cancer (IARC) and to provide information concerning colorectal cancer screening initiatives worldwide.

Data Sources and Methods

Cancer incidence data are collected by population-based cancer registries across the globe, which cover national populations or, more commonly, regions within nations. These cancer incidence data are compiled and provided by the IARC in volumes I to IX of Cancer Incidence in Five Continents (CI5).9, 10 The most recent volume of CI5 (volume IX) includes data from 225 registries in 60 countries and covers approximately 11% of the world population.9 We used data from volume IX of CI5 to display cross-sectional, aggregated colorectal cancer incidence rates for 1998–2002 for select registries. Many countries had multiple registries included in CI5; however, we restricted our presentation of the data to 2 registries per country: those with the highest and those with the lowest rates. In addition, when available, aggregates of local registries or national registries were used instead of local registries (eg, the United States and Canada). Colorectal cancer incidence data were coded according to the 10th edition of the International Classification of Diseases for Oncology (ICD-O) (C18–C21).

Mortality data are collected in all economically developed countries and some economically transitioning countries. These data, covering approximately 30% of the world population, are abstracted from death certificates and compiled in a World Health Organization mortality database, and are available to the public at the IARC website.11 The quality of mortality data vary by country, with a high accuracy of underlying cause of death noted in longstanding, economically developed countries and a lower accuracy reported in newly developed or economically transitioning countries. We used single-year mortality data to examine trends in age-standardized colorectal cancer death rates for 29 select countries with long-term mortality data using joinpoint regression analysis, which involves fitting a series of joined straight lines on a logarithmic scale to the trends in the annual age-standardized rates. The method is described in detail elsewhere.12 The resulting trends of varying time periods were described by annual percent change (APC) (ie, the slope of the line segment).12 In describing mortality trends, the terms “increase” or “decrease” were used when the APC was statistically significant (P < .05); otherwise the term “stable” was used. Countries included in the trend analysis had at least 10 continuous years of mortality data of varying length during the time period between 1985 and 2005. The majority of countries had data available for all 20 years. Colorectal cancer mortality data were coded according to the ICD edition in use at the time of death (153–154 in ICD-9 or C18–C21 in ICD-10).

Although there are differences in the etiologies and epidemiology of colon and rectal cancer, we chose to study both together to account for variances in classification that sometimes occur with tumors diagnosed at the rectosigmoid junction. All incidence and mortality rates include cancers of the colon, rectum, and anus, and we will refer to these cancers collectively as colorectal cancer. Cancer of the anus is not routinely combined with cancers of the colon and rectum in US cancer statistics, but is combined in international cancer statistics. However, anal cancer is a rare disease. For example, in the United States in 2006, the incidence rate (per 100,000) for anal cancer was 1.5 compared with 45.9 for colon and rectal cancer.13 All colorectal cancer rates were age-standardized to the 1960 world standard population to compare data across countries with different age compositions.

Information regarding international colorectal cancer screening initiatives was based on a literature review. The majority of the data were obtained from the International Colorectal Cancer Screening Network (ICRCSN) through an article published by Benson et al.14

Results

Colorectal Cancer Incidence

Colorectal cancer incidence rates vary markedly worldwide, with rates per 100,000 among males in the time period 1998–2002 reported to range from 4.1 in India (Karunagappally) to 59.1 in the Czech Republic. Among females, these rates ranged from 3.6 in India (Karunagappally) to 39.5 in New Zealand. The majority of registries with the highest incidence rates of colorectal cancer were located in Europe, North America, and Oceania. In contrast, the lowest rates were observed from registries in Asia, Africa, and South America.

Notably, colorectal cancer rates (1998–2002) among males in the Czech Republic, Japan, and Slovakia (Fig. 1) have exceeded the peak incidence rates observed in longstanding, developed nations such as New Zealand, Australia, and the United States, which previously reported the highest colorectal cancer incidence rates worldwide.3 Although data regarding risk factors for colorectal cancer are limited in many parts of the world, high colorectal cancer rates in newly developed or economically transitioning countries such as the Czech Republic and Slovakia and some others in Eastern Europe are most likely the result of the increased prevalence of obesity associated with “Westernization,” including the consumption of high-calorie–dense foods and physical inactivity.7, 15-17 In addition, elevated smoking prevalence as indicated by lung cancer mortality rates (which were noted to have peaked later and at a higher rate in the Czech Republic and Slovakia compared with longstanding, economically developed countries such as the United States3) may play a role in the elevated colorectal cancer rates reported in these countries.

Figure 1

Registries with the Highest Age-Standardized Colorectal Cancer Incidence Rates by Sex, 1998–2002. UK indicates United Kingdom; USA, United States of America; NPCR, National Program of Cancer Registries. Source: Cancer Incidence in Five Continents.9

Although the majority of the highest colorectal cancer incidence rates among males were observed in Europe, North America, and Oceania, select registries in Asia also recorded high rates in Japan, Singapore, and Israel. Increases in colorectal cancer incidence rates have been observed in these 3 countries in recent years,3 and are most likely due to environmental or lifestyle factors. In Japan, a developed country with one of the strongest economies worldwide, the high incidence of colorectal cancer, particularly among males, is most likely due to modifications in dietary intake.18 Energy intake gradually increased and then remained constant in Japan after World War II, mainly as a result of the increased intake of Western-type foods, which has contributed to increased obesity in Japan.19, 20

Among females, the highest colorectal cancer incidence rates were observed in New Zealand, Australia (Tasmania), and Israel (Fig. 1). New Zealand and Australia, in addition to many other longstanding developed nations in Europe and North America, have historically had high incidence rates of colorectal cancer that are most likely the result of behaviors associated with urbanization. However, colorectal cancer incidence rates in recent years among females have declined in New Zealand and stabilized in Australia (Tasmania), but have continued to increase in Israel.3 High colorectal cancer rates among females were also observed in the Asian registries of Japan and Singapore, although rates for females are substantially lower than those for males in these and other registries. The lower rates observed among females compared with males may be related to differences in risk behaviors associated with colorectal cancer, such as smoking,21 and the differing effect of obesity in men and women.22 In many countries, the regular uptake of smoking among women lags 20 to 30 years behind that of men.

Among both males and females, the lowest rates of colorectal cancer incidence were observed for registries in India (Nagpur, Poona, and Karunagappally), Oman, Egypt (Gharbiah), Algeria (Setif), and Pakistan (South Karachi) (Fig. 2). In these economically developing regions of the world, low colorectal cancer incidence rates may reflect a lower prevalence of known risk factors.

Figure 2

Registries with the Lowest Age-Standardized Colorectal Cancer Incidence Rates by Sex, 1998–2002. Source: Cancer Incidence in Five Continents.9

Colorectal Cancer Mortality

Mortality trend analyses for select countries have demonstrated that colorectal cancer mortality decreased in both males and females in 13 of the 29 countries considered in this analysis. These decreases were largely confined to longstanding, economically developed nations such as the United States, Australia, New Zealand, and the majority of Western Europe, including Austria, France, Germany, Ireland, and the United Kingdom (Tables 1 and 2) (Fig. 3). However, colorectal cancer mortality trends have also decreased in some Asian and Eastern European countries in which incidence rates are among the highest worldwide. In Japan, death rates decreased by 0.9% per year from 1996 through 2005 in men and by 5.0% per year from 1992 through 2005 in women (Table 3). Similarly, in the Czech Republic, in which death rates were the second highest in 2005 among both males and females (Table 4), rates decreased by 1.0% per year from 1994 through 2005 in men and by 1.2% per year from 1988 through 2005 in women (Table 2). In addition to these 13 countries in which decreasing colorectal cancer mortality rates were noted among males and females, 4 additional countries recorded decreasing mortality rates among females only, including Latvia, Slovakia, South Africa, and Spain. The decreasing mortality rates may reflect improvements in colorectal cancer treatments that increase survival23, 24 or possibly earlier detection due to opportunistic screening or symptom recognition.

Table 1. Colorectal Cancer Mortality Rate Trends with Joinpoint Analyses for 1985 Through 2005 for Select Countries in the Americas and Oceania by Sex—WHO Mortality Database

	JOINPOINT ANALYSES
	TREND 1		TREND 2		TREND 3
	YEARS	APC	YEARS	APC	YEARS	APC
North America
Canada
Male	1985–2004	−1.10*
Female	1985–1993	−2.71*	1993–2004	−1.07*
US
Male	1985–2002	−1.61*	2002–2005	−4.19*
Female	1985–2001	−1.71*	2001–2005	−3.90*
Central and South America
Mexico
Male	1985–2005	1.48*
Female	1985–2005	0.87*
Brazil
Male	1985–2004	1.96*
Female	1985–1992	0.63	1992–2004	1.72*
Chile
Male	1985–2005	1.18*
Female	1985–2005	0.55*
Ecuador
Male	1985–2005	1.05*
Female	1985–2005	1.01*
Oceania
Australia
Male	1985–2000	−1.48*	2000–2003	−6.12*
Female	1985–2003	−2.33*
New Zealand
Male	1985–1987	−6.69	1987–1992	2.27	1992–2004	−2.68*
Female	1985–2004	−1.90*

• WHO indicates World Health Organization; APC, annual percent change; US, United States.
• * The APC was statistically different from 0.

Table 2. Colorectal Cancer Mortality Rate Trends with Joinpoint Analyses for 1985 Through 2005 for Select Countries in Europe by Sex—WHO Mortality Database

	JOINPOINT ANALYSES
	TREND 1		TREND 2		TREND 3		TREND 4
	YEARS	APC	YEARS	APC	YEARS	APC	YEARS	APC
Eastern Europe
Czech Republic
Male	1986–1994	0.90*	1994–2005	−1.01*
Female	1986–1988	5.65	1988–2005	−1.24*
Slovenia
Male	1985–1996	2.94*	1996–2005	−0.88
Female	1985–1987	−7.38	1987–1995	3.33*	1995–2001	−4.01*	2001–2005	0.97
Slovakia
Male	1992–1995	4.13*	1995–2005	−1.35
Female	1992–1995	−3.70	1995–1998	7.22	1998–2005	−2.15*
Russia
Male	1985–1993	2.31*	1993–1996	−0.95	1996–2005	1.08*
Female	1985–1991	1.35*	1991–2005	0.24*
Estonia
Male	1985–2005	0.48
Female	1985–2005	−0.19
Romania
Male	1985–2005	2.94*
Female	1985–2005	1.46*
Latvia
Male	1985–2005	0.61*
Female	1985–2005	−0.08*
Western Europe
Austria
Male	1985–1993	0.89	1993–2005	−2.80*
Female	1985–1991	−0.56	1991–2005	−2.99*
Croatia
Male	1985–2005	2.04*
Female	1985–1989	4.71	1989–1995	−2.37	1995–1999	3.85	1999–2005	−1.11
France
Male	1985–2005	−1.20*
Female	1985–2005	−1.22*
Germany
Male	1985–1994	0.37	1994–2005	−1.97*
Female	1985–1994	−0.81*	1994–2005	−3.21*
Ireland
Male	1985–2005	−1.26*
Female	1985–2005	−2.40*
Spain
Male	1985–1995	3.79*	1995–2005	0.69*
Female	1985–1996	1.69*	1996–2005	−1.09*
UK
Male	1985–1991	−0.22	1991–2005	−2.32*
Female	1985–1992	−1.67*	1992–2001	−3.63*	2001–2005	−1.18*

• WHO indicates World Health Organization; APC, annual percent change; UK, United Kingdom.
• * The APC was statistically different from 0.

Figure 3

Trends in Colorectal Cancer Mortality Rates for Select Countries in Males, 1985 Through 2005. Source: World Health Organization Mortality Database. Available at: http://www-dep.iarc.fr/. Accessed December 15, 2008.

Table 3. Colorectal Cancer Mortality Rate Trends with Joinpoint Analyses for 1985 Through 2005 for Select Countries in Asia and Africa by Sex—WHO Mortality Database

	JOINPOINT ANALYSES
	TREND 1		TREND 2
	YEARS	APC	YEARS	APC
Asia
China (Hong Kong)
Male	1985–2005	0.78*
Female	1985–1998	0.90	1998–2005	−1.98
Japan
Male	1985–1996	2.09*	1996–2005	−0.86*
Female	1985–1992	1.28*	1992–2005	−5.00*
Singapore
Male	1985–2005	−1.61*
Female	1985–1998	−0.99	1998–2005	−4.36*
Korea
Male	1985–2002	7.16*	2002–2005	1.79
Female	1985–1994	10.21*	1994–2005	3.77*
Israel
Male	1985–1995	2.46*	1995–2004	−1.77*
Female	1985–1992	1.28*	1992–2004	−0.50*
Kazakhstan
Male	1985–2005	0.59*
Female	1985–2005	0.08
Africa
South Africa
Male	1993–2005	−0.08
Female	1993–2005	−1.41*

• WHO indicates World Health Organization; APC, annual percent change.
• * The APC was statistically different from 0.

Table 4. Age–Standardized Colorectal Cancer Mortality Rates for Select Countries by Sex, Ranked in Descending Order—WHO Mortality Database, 2005*

MALES			FEMALES
RANK	COUNTRY	RATE	RANK	COUNTRY	RATE
1	Slovakia	30.8	1	New Zealand	15.3
2	Czech Republic	30.0	2	Czech Republic	14.1
3	Croatia	25.0	3	Slovakia	13.4
4	Slovenia	21.0	4	Russia	12.7
5	Estonia	20.2	5	Croatia	12.0
6	Russia	19.4	6	Latvia	11.8
7	Latvia	19.2	7	Slovenia	11.7
8	New Zealand	18.3	8	Estonia	10.9
9	Ireland	17.7	9	Israel	10.6
10	Spain	17.5	9	Ireland	10.6
11	Germany	16.9	10	China (Hong Kong)	10.5
12	China (Hong Kong)	16.8	11	Germany	10.2
13	Austria	16.3	12	Australia	9.9
14	Japan	15.8	13	Singapore	9.6
15	Romania	15.6	13	Canada	9.6
16	Australia	15.2	14	Japan	9.2
17	France	14.8	15	Romania	9.1
17	UK	14.8	15	UK	9.1
17	Canada	14.8	16	Austria	9.0
18	Israel	14.5	16	Spain	9.0
19	Korea	12.7	17	France	8.7
20	Singapore	12.6	18	Kazakhstan	8.5
21	Kazakhstan	12.1	19	US	8.1
22	US	11.9	20	Korea	7.5
23	Chile	8.4	21	Chile	6.8
24	South Africa	7.7	22	Brazil	5.6
25	Brazil	5.9	23	South Africa	4.5
26	Mexico	4.0	24	Ecuador	3.5
27	Ecuador	3.4	25	Mexico	3.4

• WHO indicates World Health Organization; UK, United Kingdom; US, United States.
• * Rates for Brazil, Canada, Israel, and New Zealand are for 2004 and those for Australia are for 2003.

Increasing trends in colorectal cancer mortality rates during the most recent time period were observed among both males and females for 6 of the 29 countries examined. These increases were observed in all South American countries examined (Mexico, Brazil, Chile, and Ecuador), as well as 2 Eastern European countries (Romania and Russia) (Fig. 3). In Romania, for example, colorectal cancer mortality rates increased 2.9% per year among males from 1985 through 2005 and 1.5% per year among females during the same time period (Table 2). Although mortality rates for males and females in Russia were high and those for Romania were intermediate, mortality rates in the South American countries in 2005 were among the lowest of all countries examined (Table 4). In addition to these 6 countries, colorectal cancer mortality rates increased among males only in 5 countries including China, Croatia, Kazakhstan, Latvia, and Spain, and among females only in Korea. In fact, the largest observed increase in colorectal cancer deaths among all countries examined occurred in Korean females, in whom rates increased 10.2% per year from 1985 through 1994 and 3.8% per year from 1994 through 2005, although rates still remained relatively low (7.5 per 100,000) in the most recent year examined (2005). Colorectal cancer mortality rates among Korean males stabilized during the most recent time period (2002–2005) after increasing 7.2% per year from 1985 through 2002 (Table 3). Increasing mortality trends in these countries may be a reflection of the increasing colorectal cancer incidence trends that have been observed in economically transitioning countries worldwide.3 These increases may also illustrate a lack of colorectal cancer screening programs and interventions to reduce the effects of lifestyle and dietary changes that accompany urbanization.

In the remaining 2 countries examined (Estonia and Slovenia), colorectal cancer mortality trends stabilized in both men and women.

Colorectal Cancer Screening

The presence or absence of colorectal cancer screening programs is an important consideration when evaluating the colorectal cancer burden worldwide, because screening may increase colorectal cancer incidence in the short term through the increased detection of prevalent cases25 and reduce the incidence of colorectal cancer in the long term through the removal of precancerous polyps.26, 27 Thus, over time, screening lowers colorectal cancer mortality by reducing the incidence and/or by detecting tumors at earlier stages, which then have better prognoses.28-30 In fact, the increased use of screening has been cited as one of the most important factors responsible for the recent decline in colorectal cancer rates in the United States.31, 32

Internationally, the chosen modality of colorectal cancer screening varies, and it is likely that the cost and availability of diagnostic resources are the leading factors influencing program design. Although colonoscopy may be considered the “gold standard” for colorectal cancer screening, it requires a skilled examiner, involves greater cost, and is less convenient to the patient.33 As such, a population-based colorectal cancer screening program based on colonoscopy is more resource-intensive and less feasible in most countries, and not at all practical in low-resource countries. Therefore, although less sensitive than structural examinations, the fecal occult blood test (FOBT), which is inexpensive and easy to perform, is a more feasible colorectal cancer screening option in many areas of the world.

In the United States, current screening recommendations for the detection of adenomatous polyps and colorectal cancer in adults with average risk (thoseaged 50 years and older) include either annual stool testing with a high-sensitivity guaiac- or immunochemical-based test, periodic stool DNA testing, flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, double-contrast barium enema every 5 years, or computed tomographic colonography every 5 years.32 The structural examinations are invasive procedures that require bowel preparations and are associated with various levels of risk.29 Therefore, in cases in which resources are not available or patients are not willing to adhere to structural examination requirements, annual FOBTs, including guaiac-based tests (gFOBT) and fecal immunochemical tests (FIT), are recommended. Although gFOBT, the most commonly used stool blood test, has been shown to reduce colorectal cancer mortality by up to 33%,34 it is less sensitive than structural examinations and less effective for the prevention of colorectal cancer because it is less sensitive in detecting precancerous polyps.32 To the best of our knowledge, annual or biannual FOBT is currently the only screening method supported by evidence from prospective randomized clinical trials.34, 35

Country-specific colorectal cancer screening guidelines, recommendations, and screening programs vary greatly worldwide. The ICRCSN was established in 2003 and has documented organized screening initiatives and pilot projects that began before 2004 (Table 5).14 The majority of countries that have national screening programs in place are using FOBT (Czech Republic, Israel, and Japan), although Poland and Germany36 have initiated colorectal cancer screening with colonoscopy. A recent study of colorectal cancer screening in Europe also indicated that the United Kingdom and France have been in the process of rolling out national screening programs using FOBT over the past several years.36 However, at this time, the majority of colorectal cancer screening initiatives are not national screening programs but rather recommendations and/or guidelines with opportunistic screening available. What is in place in many North American and European countries are ongoing regional colorectal cancer research studies and/or pilot screening programs intended to evaluate the potential for implementing screening.14, 37, 38 These studies and pilot programs use a variety of screening tests alone or in combination. Italy was reported to have the largest number of studies/programs, with 8 underway that used various combinations of FOBT, colonoscopy, and flexible sigmoidoscopy.14 These pilot programs were precursors to a national campaign for colorectal cancer screening that was launched in 2005 and was expected to have involvement from all regions of Italy by 2009.36 Other European and North American countries with documented colorectal cancer screening research studies and/or pilot programs include the United States, Canada, Belgium, Denmark, France, Norway, Spain, Switzerland, and the United Kingdom (Table 5). Information regarding colorectal cancer screening programs in South America is scarce, although 1 pilot study currently underway in Uruguay using FIT with follow-up colonoscopy for patients with positive test results reported high adherence and detection rates for colorectal cancer in the study population.39

Table 5. Colorectal Cancer Screening Initiatives Worldwide, 2004

COUNTRY	INITIATIVE TYPE	MODALITY	NAME OF INITIATIVE	REGION(S)	TARGET POPULATION	AGE RANGE, YEARS	TARGET POPULATION	FUNDING SOURCE	YEAR ACTIVITY BEGAN
Europe
Belgium	Research	FS	Screening for CRC Using Sigmoidoscopy	All	HMO members	50-75	10,000	S	1993
Czech Republic	Program	FOBT	National Program of Screening for CRC	All	Population visiting FP	50+	3,700,000	CG, HI	2001
Denmark	Research	FOBT	Randomized Study of Screening for CRC with FOBT	Funen	Resident population	45-75	140,000	PC, CG	1985
France	Research	FOBT	Burgundy Study	Burgundy, Saône-et-Loire	Resident population	45-74	155,000	CG, HI	1988
	Pilot	FOBT	National Program for CRC	22 Départements	Resident population	50-74	4,500,000	CG, HI	2003
Israel	Program	FOBT	CHS National CRC Screening Program	All	HMO members	50-74	700,000	HMO	1993
Italy	Research	FS	SCORE	Arezzo, Biella, Genova, Milan, Rimini, Turin	Volunteers	55-64	256,000	PC	1995
	Pilot	FOBT FS	SCORE 2	Biella, Florence, Milan, Rimini, Turin	Resident population	55-64	122,000	LG, PC	1999
	Program	FOBT	NHS Funded Regional Screening Program	Tuscany	Residential population of 7 local health units	50-70	969,000	LG	2000
	Program	FOBT	NHS Funded Regional Screening Program	Veneto	Resident population of 4 local health units	50-69	173,000	LG	2002
	Research	FOBT TC	Accademia Multidisciplinare Oncologia Digestiva (AMOD)	65 FP centers within 9 regions	FP patients	55-64	98,992	PC	2002
	Program	FS	Un'occhiata ti salva la vita	Veneto	Residential population of 1 local health unit	60	5000	LG	2003
	Research	FOBT FS TC	SCORE 3	Biella, Florence. Milan, Rimini, Turin, Verona	Resident population	55-64	122,000	LG, PC	2003
	Program	FOBT	NHS Funded Regional Screening Program (Prevenzione Serena)	Turin, Novara	Resident population	58	17,900	LG	2003
		FS	NHS Funded Regional Screening Program (Prevenzione Serena)	Turin	Resident population	59-69	125,000	LG	2004
Norway	Research	FS only FS + FOBT	NORCCAP-1	Oslo, Telemark	Resident population	50-64	100,000	CG, PC	1999
Poland	Program	TC	Colonoscopic CRC Screening	All	FP patients	50-65	6,500,000	CG	2000
Europe
Spain	Pilot	FOBT	Catalan CRC Pilot Screening Programme	Catalonia, l'Hospitalet	Resident population	50-69	69,000	LG	2000
	Research	FOBT	Sigmoidoscopy Screening Research Project	Catalonia, Vilafranca del Penedès	Resident population	50-69	4726	LG	2004
		FS	Sigmoidoscopy Screening Research Project	Catalonia, Vilafranca del Penedès	Resident population	50-69	2023	LG	2004
Switzerland	Research	FOBT FS TC FS+ FOBT	—	Glarus, Vallée du Joux, Uri	Resident population	50-80	20,000	O	2000 F
UK	Research	FOBT	The Nottingham CRC Screening Trial	Nottingham, England	FP patients	45-74	153,000*	CG	1981
	Research	FS	UK FS Screening Trial	14 areas in England, Scotland, and Wales	FP patients	55-64	376,000	CG, PC	1996
	Pilot	FOBT	The UK Pilot of CRC Screening	England (3 areas) and northeast Scotland (2 areas)	Resident population	50-69	476,000	CG	2000
	Research	FS	Nurses Led FS Screening Study	Harrow, North London	FP patients	60-64	500	PC	2003
The Americas
Canada	Program	FS	Colon Cancer Detection Clinic	Ontario	FP patients	50+	500,000	HI	1999
	Pilot	FOBT	Ontario FOBT Pilot Study	Ontario	6 regions of FP patients, public health units	50-75	440,000	LG	2004
US	Research	FS	PLCO Cancer Screening Trial	10 states	10 clinical centers	55-74	154,000	CG	1993
	Program	FS	CoCaP (Kaiser Permanente)	Northern California	HMO members	50+	500,000	CG, HMO, O	1994
	Pilot	FOBT	FOBT in Veterans Affairs	All	Veterans Affairs patients	50+	30,000	CG	2000
	Research	TC	National Colonoscopy Study (Phase I)	3 states	HMO members, wellness clinic, resident population	50-64	975,000	CG	2000
Western Pacific
Australia	Pilot	FS	FS for CRC in Average-Risk Subjects	Fremantle, Western Australia	Resident suburban population	55-64	80,000	LG	1995
	Research	FOBT	Relative performance and acceptability of FOBT types	Adelaide, South Australia	Southern residential population	50+	100,000	CG, PC, O	1997
	Pilot	FOBT	The Australian Bowel Cancer Screening Pilot	Melbourne, Victoria; Adelaide, South Australia; MacKay, Queensland	Resident population	55-74	57,000	LG, CG	2002
Western Pacific
Hong Kong	Research	TC	Screening for CRC in Chinese	All	Resident population	50-70	480,000	PC	2000
Japan	Program	FOBT	National CRC Screening Program	All	National health insurance holders	40+	35,000,000	CG, S	1992
Taiwan†	Pilot	FOBT	Keelung Community- based Integrated Screening	Kelung, Northern Taiwan	Resident population	50-79	81,000	LG	1999

• FS indicates flexible sigmoidoscopy; CRC, colorectal carcinoma; HMO, health maintenance organization; S, self-funded; FOBT, fecal occult blood test; FP, family practitioner; CG, central government; HI, health insurance; PC, private/charity; CHS, Group Health Center for Health Studies; LG, local government; NHS, National Health Service; TC, total colon; NORCCAP-1, Norwegian Colorectal Cancer Prevention Trial 1; O, other; UK, United Kingdom; US, United States; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer; CoCaP, Colorectal Cancer Prevention Program.
• * Size of trial population.
• † Not a country defined in the World Health Organization regions, but is located in the Western Pacific.
• Source: Benson VS, Patnick J, Davies AK, Nadel MR, Smith RA, Atkin WS. Colorectal cancer screening: a comparison of 35 initiatives in 17 countries. Int J Cancer. 2008;122:1357–1367.

Although nationally organized screening programs are limited to only a few countries, policies and other programs can still effectively support the availability and use of colorectal cancer screening. In the United States for example, colorectal cancer screening for persons aged 65 years and older is covered by Medicare,40 the majority of states have legislation in place to ensure private health insurance coverage for colorectal cancer screening,40 and government-sponsored demonstration programs focus on colorectal cancer screening for low-income persons with inadequate health insurance.41 In addition, a measure called the Healthcare Effectiveness Data and Information Set (HEDIS) can help employers evaluate health plans' colorectal cancer screening performance, and is widely regarded as a stimulus to health plans to increase colorectal cancer screening rates.42 These and other policies/programs most likely influenced the high rate of adoption of colorectal cancer screening in the United States and may have contributed to the low and decreasing colorectal cancer mortality rates noted in the country as well.

To the best of our knowledge, Japan is the only country in the Western Pacific region with a longstanding colorectal cancer screening program in place. Japan incorporated colorectal cancer screening using FOBT into its public health policy in 1992 and this in part may have contributed to the increase in colorectal cancer incidence rates noted in Japanese registries in the mid to late 1990s.43, 44 National guidelines are available in Australia, Korea, and Singapore,45 and research studies and/or pilot programs for colorectal cancer screening have been implemented in Australia, Hong Kong, and Taiwan.14 Taiwan is the only country in the region with free mass colorectal cancer screening available under its national health insurance program.45 In contrast, most Asian countries have very little governmental support for colorectal cancer screening and lack any kind of colorectal cancer screening initiative, including screening guidelines (eg, Brunei, China, India, Indonesia, Malaysia, the Philippines, Thailand, and Vietnam).45 The need for mass colorectal cancer screening in the economically developing countries of Asia, South America, and Africa is occasionally questioned given the lower rates of colorectal cancer, the substantial burden of communicable diseases, and the limited resources in these areas.46 However, because colorectal cancer mortality rates are increasing in many economically developing countries, particularly those that are transitioning to Western lifestyles or have aging populations, consideration of implementing targeted screening for colorectal cancer is likely to increase over time.

Conclusions

Worldwide, colorectal cancer incidence rates are highest in the registries of newly economically developed countries such as the Czech Republic and Slovakia in Eastern Europe, and also remain high in longstanding, economically developed countries such as Japan and Australia as well as the majority of registries in Western Europe and North America. Decreasing colorectal cancer mortality rates, most likely due to colorectal cancer screening and/or improved treatment, have been observed in a large number of countries examined; however, increases in mortality rates are still occurring in countries that may have more limited resources, including Mexico and Brazil in South America and Romania and Russia in Eastern Europe, compared with longstanding, economically developed countries.

The current study was limited by data availability, because incidence data are not available for all countries and in most instances are only region-specific. Although mortality data are more complete, it is possible that the increasing mortality trends noted in some countries could be the result of improvements in death certification systems or data abstraction.

The increasing prevalence of obesity and decreasing physical activity in many parts of the world, resulting from “Westernization,” will likely continue to contribute to the growing international colorectal cancer burden if these behaviors are not modified. In addition, as people continue to live longer, colorectal cancer will become an even greater public health problem worldwide. Colorectal cancer screening has been proven to greatly reduce mortality and in some instances may prevent the onset of disease through the removal of precancerous polyps. The variety of existing screening tests makes colorectal cancer screening accessible for most countries, and therefore, greater international consideration of targeted screening programs and/or screening recommendations could help to alleviate the burden of colorectal cancer worldwide.