1. Prof. John K. Triantafillidis
Descriptive epidemiology of colorectal cancer: The size of the problem and the significance of preventive Strategies
Mr Chairman, Thank you very much for your kind words although I feel that they are too good to be true.
Dear colleagues, good morning, during the next 30 minutes I would attempt to introduce all of us into the amazing world
of the science of epidemiology of CRC.
In my opinion, the epidemiological parameters of this disease and their correct interpretation could
not only give us an idea about the statistics of the disease but also can create hypotheses concerning its etiology.
Prof. John K. Triantafillidis

2. Objectives The size of malignancies worldwide
The size of malignancies in Europe
Epidemiology of CRC worldwide
Epidemiology of CRC in Europe
Preventive strategies: description and significance
The aim of this presentation is to describe the CRC incidence and mortality patterns and trends, and link the findings
to the prospects of reducing the burden of CRC through preventive strategies.

3. Design
Sex-specific CRC incidence and mortality rates in 2012, were extracted from the GLOBOCAN database.
Temporal patterns were assessed using data from Cancer Incidence in Five Continents and the WHO mortality database.
In order to achieve this task we extracted the CRC incidence and mortality rates in various parts of the world by
using data from Globocan database, and from cancer incidence in five continents.

4. CANCER INCIDENCE WORLDWIDE
Let’s start by realizing the incidence and prevalence of cancer worldwide using the relevant numbers

5. The number of new cases of cancer is expected to rise 70% over the next 2 decades.
Cancer is one of the leading causes of morbidity worldwide with 14 million new cases in 2012.
Generally speaking cancer was responsible for 14 million new cases in 2012.
In the next two decades the number of new cases of cancer is expected to rise by 70% at least.

6. CANCER MORTALITY WORLDWIDE
The features of mortality from cancer are also quite worrying.

7. Cancer was responsible for 8.8 million deaths in 2015.
Cancer is the second leading cause of death globally.
8.8 million people died from cancer in 2015, thus making cancer the second leading cause of death globally.

8. Deaths from CRC globally
Lung (1.69 million)
Liver (788,000)
Colorectal (774,000)
Stomach (754,000)
Breast (571,000)
Specifically CRC corresponds to the third leading cause of death globally, after lung and liver cancer
being responsible for 775,000 deaths

9. Sex ratio
The overall age standardized cancer incidence rate is 25% higher in men than in women, with rates of 205 and 165/100,000, respectively.
Globally the standardized incidence rates are quite higher in men than in women.

10. 79 vs 365 in Africa and Australia respectively.
Male incidence rates vary almost fivefold across the different regions of the world…
…with rates ranging from 79/100,000 in Western Africa to 365/100,000 in Australia/New Zealand.
It is of great interest that the incidence rates of cancer significantly differ in different parts of the world
79 vs 365 in Africa and Australia respectively.

11. This variation in the incidence rates is less prominent in women.
There is less variation in female incidence rates (threefold)...
...with rates ranging from 103/100,000 in South-Central Asia to 295/100,000 in Northern America.
This variation in the incidence rates is less prominent in women.
In fact, incidence does not exceed a threefold rate comparing South-Central Asia and North America.

12. Now let’s see the situation in our continent
CANCER IN EUROPE
Now let’s see the situation in our continent

13. With 3. 7 million new cases and 1
With 3.7 million new cases and 1.9 million deaths each year, cancer represents the second most important cause of death and morbidity in Europe.
Europe represents 1/8 of the world population but has one quarter of the global cancer cases.
Cancer in Europe represents the second most important cause of death and morbidity with 3.9 million cases
in 2015 and almost 2 million deaths. In order to get a general idea about the problem of cancer in Europe, first we have to realize
that, although Europe represents 1/8 of the world population, it has the one quarter of global cancer cases.

14. CANCER ECONOMIC IMPACT
Key points
The economic impact of cancer is significant and continuously increasing.
The total annual economic cost of cancer in 2010 was estimated approximately at US$ 1.16 trillion.
The economic impact of cancer is also quite significant and more importantly, it is continuously rising.
It has been estimated that in 2010 almost 1.2 trillion USA$ were spent for cancer care worldwide.

15. COLORECTAL CANCER WORLDWIDE
Now, let’s see firstly the CRC epidemiological features worldwide.

16. CRC INCIDENCE RATES WORLDWIDE
1,360,602 new cases
3rd most common cancer
9.7% of all cancers
(2012 GLOBOCAN)
According to Globocan estimations, in 2012, with almost 1.4 million new cases CRC represents
the 3rd common cancer globally, corresponding to nearly 10% of all cancer cases.

17. corresponding to 8.5% of the total number of cancer deaths.
CRC MORTALITY RATES WORLDWIDE
693,933 deaths
8.5% of the total number of cancer deaths
4th most common cause of cancer related deaths
(2012 GLOBOCAN)
Also, in 2012 with almost deaths CRC represents the 4th most common cause of cancer related deaths
corresponding to 8.5% of the total number of cancer deaths.

18. 68.2 survivors/100,000 population
COLORECTAL CANCER
5-year prevalence worldwide
3,543,582 patients or
68.2 survivors/100,000 population
(2012 GLOBOCAN)
Let’s move on to the prevalence –that is the number of patients who are still alive 5-years after diagnosis of CRC.
In 2012, more than 3.5 million CRC patients corresponding to 68% survivors per population, were still alive worldwide.

19. COLORECTAL CANCER IN EUROPE

20. CRC INCIDENCE IN EUROPE
447,136 new cases
2nd most common cancer
13.0% of all cancers
(2012 GLOBOCAN)
With nearly 500,000 new cases annually CRC represents the second most common cancer in Europe

21. CUMULATIVE RISK OF CRC IN EUROPE (2012) (persons aged <75)
Worldwide
Total
3.51%
1.95%
Men
4.48%
2.36%
Women
2.73%
1.57%
This slide shows the cumulative risk of CRC in Europe in individuals under the age of 75.
It is clearly shown that the cumulative risk in Europe is higher in both men and women compared to the relevant features worldwide.

22. CRC MORTALITY IN EUROPE
214,866 deaths
2nd most common cause of cancer related deaths
12.2% of the total number of cancer deaths
(2012 GLOBOCAN)
Regarding mortality from CRC, with deaths annually this malignant neoplasm corresponds to
the 2nd most common cause of cancer related deaths.

23. 5-year prevalence in Europe
COLORECTAL CANCER
5-year prevalence in Europe
1,203,943 patients Or
192.3 CRC survivors/100,000 population
(2012 GLOBOCAN)
Regarding the 5-year prevalence in Europe the corresponding features were 192 survivors per population
or 1.2 million alive patients

24. and developing countries in both men and women.
This rather complicated slide shows both the incidence and mortality rates from CRC in different parts of the world.
The blue color corresponds to the incidence and the red one to mortality.
There are significant differences in both epidemiological parameters between developed
and developing countries in both men and women.

25. In the next slides I will show you some figures concerning the incidence and mortality rates in certain countries of the world.
This figure shows the incidence rate of CRC in men in certain European countries.
We can see the rising incidence of CRC over the last 3 decades as well as the significant differences between these European countries
Trends in incidence of CRC in selected countries: age-standardized rate /100,000, men

26. compared to the previously shown European countries
This figure underlines the rising incidence of CRC in some Asian countries. We can see the generally lower incidence
compared to the previously shown European countries
Trends in incidence of CRC in selected countries: age-standardized rate / 100,000, men

27. Please note the significant difference in the incidence rates between Australia, USA and Canada, and Colombia and Costa Rica. Also note the declining incidence of the disease in the USA population.
Trends in incidence of CRC in selected countries: age-standardized rate / 100,000, men

28. Please note also the declining rate of mortality in some of them.
Even among the European countries the mortality rates differ significantly, e.g. Slovakia vs Finland.
Please note also the declining rate of mortality in some of them.
Trends in mortality from CRC in selected countries: age-standardized rate /100,000, men

29. The mortality rate of CRC is decreasing during the last 3 decades in North America and Australia, while it is rising in countries of South America.
Trends in mortality from CRC in selected countries: age-standardized rate /100,000, men

30. Estimated CRC incidence in 2012: Women
Except Slovakia, the estimated CRC incidence in 2012 in women in certain European countries is almost the same.
Estimated CRC incidence in 2012: Women

31. Estimated CRC incidence in 2012: Women
The same trends can be seen in countries of North America but not in those of South America
Estimated CRC incidence in 2012: Women

32. Estimated CRC incidence in 2012: Women
The incidence rates among women in Singapore and Japan are the same during the last decades.
Note the very low incidence in India
Estimated CRC incidence in 2012: Women

33. Estimated CRC mortality in 2012: Women
The mortality rate among women in certain European countries is decreasing
Estimated CRC mortality in 2012: Women

34. Estimated CRC mortality in 2012: Women
The mortality rate among women is rising in the Republic of Korea, remaining steady in Japan and declining in Singapore
Estimated CRC mortality in 2012: Women

35. Estimated CRC mortality in 2012: Women
The mortality rate among women during the last decades is continuously declining in North America
but it is slightly rising in South America
Estimated CRC mortality in 2012: Women

36. The Growing Challenge of Young Adults With Colorectal Cancer
B. Weinberg,
J. Marshall,
M. Salem,
May 16, 2017
In the USA population the rates of CRC are rising among adolescent and young adults
(a population not suitable for screening colonoscopy). Clinicopathologic features and tumor biology (methylation status, MSI, and somatic mutations) in young patients contrast with older ones, explaining at least in part the observed differences.

37. At least in the USA it seems that younger patients with CRC tend to have more distal cancer than older patients

38. Trends in CRC incidence and mortality:
three groups of temporal pattern
Group 1:
incidence ↑
mortality ↑
Philippines, China, Colombia, Bulgaria, Costa Rica, Brazil, Russia, Belarus, Estonia, Lithuania, Croatia, Spain, Latvia, Poland
Group 2:
mortality ↓
Canada, Denmark, Switzerland, Ireland, Sweden, Singapore, Finland, Norway, Slovakia, UK, Netherlands, Italy, Malta, Slovenia
Group 3:
incidence ↓
US (White), US (Black), Austria, New Zealand, Czech Republic, Iceland, France, Japan, Australia, Israel
Based on temporal characteristics of incidence and mortality, three different groups of countries could be found
Group 1: those with increasing or stable incidence and mortality (14 countries),
Group 2: those with increasing incidence and decreasing mortality (14 countries)
Group 3: those with decreasing incidence and mortality (9 countries).
Arnold M, et al. Gut 2016;0:1-9

39. Group 1: increasing incidence and mortality
Increase in both incidence and mortality rates over the most recent 10-year period in men was seen in Eastern European countries, and in Latin America and Asia.
The largest increase in incidence was seen in Brazil, Costa Rica and Bulgaria.
In females, trends were similar to those in males
Arnold M, et al. Gut 2016;0:1-9

40. Group 2: increasing incidence and decreasing mortality
These trends were observed in several European countries, as well as in Canada and Singapore.
Stable trends were observed in Northern European countries.
A declining mortality rate was observed in the UK, along with a small increase in incidence rate.
Arnold M, et al. Gut 2016;0:1–9

41. Group 3: decreasing incidence and mortality
Decreases in both CRC incidence and mortality rates were restricted to the countries with the highest human development index, such as Australia, New Zealand and Japan.
Again, patterns were similar for males and females.
Arnold M, et al. Gut 2016;0:1–9

42. … In summary
The distribution of CRC burden varies widely, with more than 2/3 of all cases and about 60% of all deaths occurring in countries with a high or very high human development index.

43. Rapid increases in both CRC incidence and mortality rates are now observed in many medium-to-high human development index countries, particularly in Eastern Europe, Asia and South America.

44. In contrast, CRC incidence and mortality rates have been stabilizing or declining in some of those countries with the highest human development index: the USA, Australia, and several Western European countries.

45. The reasons for the declining trends in incidence rate in these countries may reflect an increased early detection and prevention through polypectomy.

46. Improvements in perioperative care, chemotherapy and radiotherapy, have contributed to the decreasing trends in CRC mortality in many high income settings.

47. Future predictions
Given the temporal profiles and demographic projections, the global burden of CRC is expected to increase by 60% to more than 2.2 million new cases and 1.1 million cancer deaths by 2030.
Arnold M, et al. Gut 2016;0:1–9

48. Epidemiological features of CRC in Greece
I would like to show you some epidemiological features of CRC in Greece, a country located in the South Europe
having some special lifestyle characteristics, including the so-called Mediterranean diet.

49. Greece: Demographic data
Population in 2012:
11.4m
People newly diagnosed with cancer per year
41,000
Age-standardised rate, incidence per 100,000 people per year
163.0
Risk of getting cancer before age 75
16.0%
People dying from cancer per year
28,500
According to Globocan data in a population of 11.4 million people, the life expectancy is among
the highest globally, and the rates of cancer are among the lowest in Europe.
Life expectancy at birth (m/f ) (years)
78/84
Data from IARC GlobalCan (2012)

50. Incidence and mortality from cancer in Greece (men)
In this slide we can see the estimated incidence and mortality rates from various cancers including CRC among men.
CRC occupies the 4th position in the incidence and the third position in mortality rates.

51. Incidence and mortality from cancer in Greece (women)
This figure shows that in women CRC occupies the second position in the incidence and the third position in mortality rates.

52. Incidence and mortality from cancer in Greece (both sexes)
In both sexes, CRC in Greece occupies the 4th position in incidence as well as in mortality rates among all cancers

53. In summary…
In Greece CRC is among the 4 leading causes of cancers in both sexes.
The lower incidence rates in comparison with other European countries could be attributed to many factors including environmental (diet) and genetic ones.

54. THE SIGNIFICANCE OF PREVENTIVE STRATEGIES
COLORECTAL CANCER
THE SIGNIFICANCE OF PREVENTIVE STRATEGIES

55. Risk of Colorectal Cancer
General
population 5%
Personal
history of CRC
15%–20%
IBD
15%–40%
It is well established that the risk of getting CRC is increasing under certain circumstances including history of CRC,
IBD, hereditary CRC syndrome and familiar polyposis syndromes
HNPCC
70%-80%
>95%
FAP 40 20
Lifetime risk (%) 60 80
100 3

56. Affected family members
70%
Approximate
lifetime
CRC risk
(%)
17% 8%
10% 6% 2%
Also the approximate lifetime CRC risk is increasing depending on the number of the affected family members
None
One 1°
One 1° and two 2°
One 1° age <45
Two 1°
HNPCC mutation
Affected family members

57. In a systematic review of the literature, the authors found that…
Risk of CRC in UC
Among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%.
Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD were features associated with dysplasia progression.
In a systematic review of the literature, the authors found that…
Clin Gastroenterol Hepatol, 2017;15:

58. The significance of lifestyle
CRC incidence and mortality rates correlate with the adoption of a western lifestyle.

59. Relation to income
Incidence and mortality rates are still rising rapidly in many low and middle- income countries.

60. the lack of appropriate chemo and radiation therapy
Approximately 70% of deaths from cancer occur in low- and middle-income countries.
In low and middle income countries cancer is responsible for 70% of all cancer deaths due to, among others,
the lack of appropriate chemo and radiation therapy

61. This slide shows the Cancer Incidence and Mortality rates worldwide by Income Level, in 2012.
As indicated, both the incidence and mortality rates are significantly higher in low and middle income
countries compared to countries with high income, in all types of cancer.

62. Reducing the burden of CRC
Do we have strategies to reduce the burden of CRC?

63. Decrease in incidence rates in countries with a high human development index is likely driven by changes in lifestyle and dietary patterns over the past decades.
It is possible that …

64. The rapid transition in income and economic growth in low and middle- income countries has shifted dietary patterns towards an increased intake of fat, sugar and animal-source foods.

65. The access to cheaper ‘junk’ food was paralleled by a reduction in physical activity and an increase in sedentary behavior, fuelled by an increase in obesity.

66. According to a recently published paper …
A proinflammatory diet replete with red meat, among other foods, increases the risk of CRC in both men and women.
It is especially risky in overweight and obese men, as well as, paradoxically, in lean women.
According to a recently published paper …
 JAMA Oncology, published online, January 2018.

67. Modifiable risk factors
Alcohol consumption
Poor diet (low consumption of fruits and vegetables, and high consumption of red/processed meat)
Obesity
Physical inactivity
Smoking
Well known harmful factors including excessive alcohol consumption, low consumption of fruits and vegetables
and high consumption of red meat, obesity, physical inactivity and smoking, must be abandoned or modified.
“We can modify our states of inflammation through our diet and lifestyle”

68. So, CRC risk can be reduced through a healthy lifestyle including…
No smoking
Maintaining a healthy body weight
Staying physically active
Adopting a diet low in red and processed meat and high in fiber
Minimizing alcohol consumption
So, CRC risk can be reduced through a healthy lifestyle including…

69. Screening Strategies
CRC can also be prevented through screening, which can remove precancerous lesions and detect cancer early.

70. Early detection and screening might have led to short-term increase in incidence.
These interventions will contribute to mortality reduction through the detection of CRC in early stage.

71. CRC screening methods Colonoscopy Fecal occult blood test
Highly sensitive test. It involves the highest cost.
Fecal occult blood test
Inexpensive, easy to perform. The more practical option in many parts of the world.
Fecal immunochemical test
It is preferred to the guaiac-based FOBT due to the lack of dietary restriction requirements and its higher specificity.
Noninvasive stool DNA test
It has been developed and approved by the FDA.
Several options for colorectal cancer screening are available, although they vary in cost and other requirements.

72. As of 2014, 36 countries with high income and high incidence of CRC, adopted screening programs.
Screening programs may not be recommended in countries where CRC incidence is low.
Countries with low rates but a rapidly “westernizing” lifestyle are now experiencing increasing CRC rates that merit a screening program using FOBT.

73. Established protective factors
Aspirin
Estrogens after menopause
Vitamin D
Established protective factors that could partly explain a stabilization of incidence rates in high-income countries
include the regular use of aspirin, vitamin D and estrogens

74. Conclusions
High rates of CRC are found in Europe, Australia, and North America.
The lowest rates are found in Africa, and in some Asian countries, and Latin America.

75. Increases in mortality rate have been reported in several countries in Latin America, and Asia, that may reflect limited health infrastructure and poorer access to early detection and treatment.

76. CRC incidence and mortality rates are still rising in many low- and middle income countries.
Stabilizing or decreasing trends tend to be seen in highly developed countries where rates remain among the highest in the world.

77. The increase observed in Latin America, Asia, and Eastern Europe may be due to rapidly changing diet patterns and increased smoking over the past several decades.

78. The decreasing rates in the USA can be attributed largely to screening and removal of precancerous lesions, as well as reductions in risk factors, which have contributed to decreases in other countries too.
Incidence rates in the USA and Australia are increasing in adults <50 years.

79. Suggestions
In order to reduce the number of patients with CRC within the next decades, we need targeted interventions, including primary prevention in low- income, supplemented with early detection in high income, settings.

80. THANK YOU FOR YOUR ATTENTION