Updates Surg

DOI 10.1007/s13304-016-0359-y

REVIEW ARTICLE

Worldwide burden of colorectal cancer: a review

Pasqualino Favoriti1 • Gabriele Carbone1 • Marco Greco1 • Felice Pirozzi1 •

Raffaele Emmanuele Maria Pirozzi2 • Francesco Corcione1

Received: 22 January 2016 / Accepted: 9 March 2016

Ó Italian Society of Surgery (SIC) 2016

Abstract Colorectal cancer is a major public health Introduction

problem, being the third most commonly diagnosed cancer
and the fourth cause of cancer death worldwide. There is Colorectal cancer (CRC) is among the leading causes of
wide variation over time among the different geographic mortality and morbidity throughout the world, thus repre-
areas due to variable exposure to risk factors, introduction senting a major public health problem. It is the third most
and uptake of screening as well as access to appropriate common cancer worldwide (following tumors of the lung
treatment services. Indeed, a large proportion of the dis- and breast), and the fourth most common cause of onco-
parities may be attributed to socioeconomic status. logical death [1].
Although colorectal cancer continues to be a disease of the Epidemiological data vary over time among the differ-
developed world, incidence rates have been rising in ent geographic areas due to variable exposure to risk fac-
developing countries. Moreover, the global burden is tors, introduction of preventive measures, and evolution of
expected to further increase due to the growth and aging of treatments. Accurate statistics on cancer occurrence and
the population and because of the adoption of westernized outcome are essential, both for the purposes of research and
behaviors and lifestyle. Colorectal cancer screening has for the planning and evaluation of programs for cancer
been proven to greatly reduce mortality rates that have control [2].
declined in many longstanding as well as newly econom- The aim of this paper is to provide a comprehensive
ically developed countries. Statistics on colorectal cancer overview of incidence, mortality and survival rates for
occurrence are essential to develop targeted strategies that CRC as well as their geographic variations and temporal
could alleviate the burden of the disease. The aim of this trends.
paper is to provide a review of incidence, mortality and
survival rates for colorectal cancer as well as their geo-
graphic variations and temporal trends. Incidence

Keywords Colorectal cancer
Incidence
Mortality
CRC is the third most commonly diagnosed cancer in
Epidemiology males and the second in females worldwide. It accounts for
over 9 % of all cancer incidence, with an estimated 1.4
million cases occurring in 2012 [1, 2].
There is wide geographical variation in incidence across
& Felice Pirozzi the world, with almost 55 % of the cases occurring in more
felice.pirozzi@hotmail.it developed countries [3]. These geographic differences may
1 be attributable to different dietary and environmental
Department of General and Laparoscopic Surgery, Azienda
Ospedaliera dei Colli-Monaldi Hospital, Via Leonardo exposures that are imposed upon a background of geneti-
Bianchi, 80131 Naples, Italy cally determined susceptibility [4].
2
School of Medicine and Surgery, University of Naples Countries with the highest incidence rates include
Federico II, Via Sergio Pansini 5, 80131 Naples, Italy Australia, New Zealand, Europe and Northern America.

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Conversely, incidence rates are low in Africa, South-Cen- on 323,888 White and Black cases of CRC diagnosed
tral Asia and Central America [1, 5]. Based on the during the years 1975 to 2002 from the Surveillance,
2007–2011 data from the Italian Association of Cancer Epidemiology, and End Results Program (SEER) registries
Registries, CRC was the second most common cancer after in the United States. The authors found that CRC rates
breast cancer. At present, CRC is the most frequent cancer were higher among Blacks than Whites. These racial dis-
in the Italian population, with almost 52,000 new estimated parities most probably reflected complex interactions
cases in 2015. In men, it is the third most common cancer between screening and etiologic factors, that may also be
after tumors of the prostate and lung, accounting for 14 % influenced by socioeconomic status [22]. Indeed, the 2000
of all cancer incidence. In women, CRCs account for 13 % National Health Interview Survey showed that fewer
of all new cancers and are the second most frequent tumors Blacks than Whites had routine screening [23]. With regard
after those of the breast [6]. Globally, incidence rates vary to etiologic factors, some biological differences in car-
tenfold, the highest estimated rates being in Australia/New cinogenic risk and/or exposures may exist. Blacks com-
Zealand (age-standardized ratio 44.8 and 32.2 per 100,000 pared with Whites were more likely to have younger age at
in men and women, respectively), and the lowest in Wes- diagnosis, proximal or transverse CRCs, and lower tumor
tern Africa (4.5 and 3.8 per 100,000). Geographic patterns grade [21]. The etiologic role for promotional factors in
are very similar in both sexes [3]. CRC is also highlighted by studies on migrants [14].
Trends in high-risk/high-income countries have varied Incidence rates are substantially higher in men than in
over the last two decades, being either declining (United women in most parts of the world [1]. The reasons for this
States), stabilizing (France and Australia), or gradually variability are not completely understood, but likely reflect
increasing (Finland, Norway, Spain) [1]. The most marked complex interactions between sex-specific exposure to risk
changes occurred in the United States, where CRC inci- factors and protective effects of both endogenous and exoge-
dence rates have declined about 2 to 3 % per year over the nous hormones as well as gender-specific differences in
last 15 years [7]. Notably, the decrease was observed screening practices [24, 25]. Gender disparity varies by age. For
among people aged 50 years and older, which is primarily example, in the United States, the male-to-female incidence
associated with the increase in screening uptake and ratio was found to be 1.1 from birth to 49 years, 1.4 for patients
removal of precancerous adenomas [8]. At present, CRC is aged 50 to 79 years, and 1.2 for those 80 years and older [20].
the third most common cancer in both men and women in CRC incidence rates rise with increasing age [26]. CRC
the United States. In 2015, there are projected to be is uncommon among people aged 40 or younger; the
132,700 (69,090 men and 63,610 women) newly diagnosed incidence begins to raise significantly between the ages of
with colorectal cancer, accounting for an incidence rate of 40 and 50, and age-specific incidence rates further increase
8 % in both sexes [9]. in each succeeding decade thereafter [4]. However, some
On the other hand, CRC incidence rates have been rising data from cancer registries reported a rising incidence of
in developing countries [10]. The greatest increases have large bowel cancer, particularly rectal cancer, among
been observed in Western Asia (Kuwait and Israel) and young adults, even under 40 years of age [27, 28].
Eastern Europe (Czech Republic, Slovakia and Slovenia). Several studies reported a shift in the colonic site
This raise may reflect an increased prevalence of risk factors localization of CRC over time, with a higher proportion of
for CRC that are associated with westernization such as tumors occurring in the right colon [29]. An increased
unhealthy diet, obesity and smoking prevalence [11–13]. proportion of proximal compared to distal tumors has been
Moreover, the global burden of CRC is expected to further reported in females than males [30] as well as in older than
increase due to growth and aging of the population [14–16]. younger people [31]. Although biologic changes may have
Low socioeconomic status is associated with an occurred, this shift in the anatomic site of CRC may be
increased risk for CRC. A study on 7676 patients diag- partly related to increased screening, which is more
nosed with primary CRC among 506,488 participants, effective in detecting and preventing left-sided than right-
found a significantly higher incidence rate among people sided CRCs [32].
who had low educational level or lived in low-socioeco-
nomic status neighborhoods, compared with the highest
status-groups, even after accounting for other risk factors Mortality
[17]. This difference may be due to a higher incidence of
potentially modifiable risk factors (physical inactivity, CRC is the fourth most common cause of cancer death in
unhealthy diet, smoking, obesity) as well as low rates of men and the third in woman worldwide. Almost 693,900
CRC screening [18, 19]. deaths from CRC are estimated to have occurred in 2012,
Variations exist in CRC incidence among different accounting for approximately 8 % of all cancer deaths [1,
races/ethnicities [20]. Irby et al. [21] conducted an analysis 33, 34].

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There is less variability in mortality rates worldwide be associated with later CRC stage at diagnosis and less
(sixfold in men, fivefold in women), with the highest aggressive treatment [22]. However, other factors may
mortality rates in both sexes estimated in Central and contribute to the higher burden in Blacks, since CRC death
Eastern Europe (20.3 per 100,000 for males, 12.1 per rates are substantially higher in Blacks than in Whites even
100,000 for females), and the lowest in Middle Africa (3.5 within the same socioeconomic gradient [42].
and 2.7, respectively) [2]. Center et al. [12] conducted a
study about mortality trends for 29 selected countries. The
authors found that CRC mortality rates have declined in Survival
many longstanding as well as newly economically devel-
oped countries such as the United States, Australia, New As for both incidence and mortality, survival rates vary by
Zealand, the majority of Western Europe (Austria, France, race/ethnicity [43]. Most of the marked global and regional
Germany, Spain, Ireland, and the United Kingdom), some disparity in survival is likely due to differences in access to
Asian (Japan) and Eastern European countries (Czech diagnostic and treatment services [5].
Republic, Latvia, Slovakia), and South Africa. These Large differences in survival rate according to stage of
improvements in mortality rates are thought to be a result disease at diagnosis are observed worldwide [14, 44]. In
of CRC prevention and earlier diagnosis through screening the United States, the 5-year relative survival rate for all
as well as reduced prevalence of risk factors, and/or stages combined increased from 50.6 to 65.4 % for colon
availability of improved treatment regimens [8, 35]. In cancer and from 48.1 to 67.7 % for rectal cancer since the
Italy, CRC was the second most common cause of cancer mid-1970s [45]. These gains likely reflect both internal
death (preceded by lung cancer in men and breast cancer in (within stage) and external (toward more localized disease)
woman), with 19.202 cases occurred in 2012. CRC mor- stage shifts as a result of earlier detection as well as
tality rates have been decreasing since 1999 of 0.6 % per improvements in treatment [20]. Overall, the 1- and 5-year
year in men and 1.2 % per year in women [6]. However, relative survival rates for patients with CRC are 83.4 and
increases in mortality rates are still occurring among both 64.9 %, respectively; survival declines to 58.3 % at
males and females in some low-resource countries, 10 years after diagnosis. When CRCs are detected at an
including Mexico, Brazil, Chile and Ecuador in South- early stage, the 5-year survival rate is as high as 90 %;
Central America and Romania and Russia in Eastern Eur- however, only 39 % of tumors are diagnosed at this stage,
ope [12, 36, 37]. Increasing mortality rates may reflect mainly due to underuse of screening. For cancers with
increasing CRC incidence trends as well as a lack of pre- regional involvement of adjacent organs or lymph nodes,
vention measures [12]. the 5-year survival rate drops to 70.4 %, and further
In the United States, CRC was the most common cause of declines to 12.5 % when the disease has spread to distant
death for tumor between 1940 and 1950 [38]. Mortality rates organs [33, 46]. Patients aged younger than 65 years were
have been decreasing since 1980 in men and since 1947 in found to have higher 5-year survival rates than those
women, with a decline of 26 % in CRC mortality for 65 years and older (68.9 vs 62.0 %). Curiously, however,
1975–2000. This improvement has been estimated to be due this advantage was confined to distal cancers; the 5-year
to improved medical treatment (12 %), changed risk factors survival rate for patients with proximal tumors was the
(35 %), and increased uptake of screening (53 %) [8]. From same (about 65 %) for each age group [31].
2001 to 2010, rates decreased by approximately 3 % per year A recent study analyzed survival data submitted by 279
in both sexes [20]. In 2015, CRC was the third expected population-based cancer registries in 67 countries for 25.7
cause of cancer death, with 49,700 expected cases (26,100 million adults (age 15–99 years) and 75,000 children (age
deaths among males and 23,600 among females) [9]. 0–14 years) diagnosed with cancer during 1995–2009 [47].
Mortality vary substantially by sex and race. Rates are Five-year survival for colon and rectal cancer reached
30 to 40 % higher in men than in women overall [20]. In 60 % or more in 22 countries around the world. For colon
the United States, mortality rates in Blacks (29.4 per cancer, survival rates surpass 60 % in North America,
100,000) are approximately 50 % higher than in Whites. Oceania, 12 European countries, and a few countries in
The latter historically experienced higher CRC mortality Central and South America and Asia; rates were 40–49 %
rates than Blacks. The racial crossover from higher to in Argentina, Bulgaria, Chile, Colombia, Latvia, and
lower mortality rates occurred during the 1970s [39]. Russia, and less than 40 % in India, Indonesia, and Mon-
Possible reasons for these differences include environ- golia. In most countries, 5-year survival from colon cancer
mental factors, a delay in the introduction of screening and increased from 1995–1999 to 2005–2009, but it fell in
a different management of the disease [40, 41]. Most of this Argentina and Cyprus. For rectal cancer, survival was very
disparity is due to the disproportion in socioeconomic high (70 % or more) in Cyprus, Iceland, and Qatar, and
status [17]. Indeed, low socioeconomic status was found to high (60–69 %) in South Korea, North America, Oceania,

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Conflict of interest The authors declare that they have no conflict
Chronic Dis Can 31:71–78
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