The document discusses various topics related to cancer epidemiology. It provides statistics showing that lung, breast, colon, stomach, prostate, liver and cervix cancers are among the most common types of cancer. It also discusses factors contributing to cancer deaths, finding that tobacco use accounts for 30%, diet 35%, infections 10%, and other factors like occupation, pollution and genetics account for smaller percentages. The document also discusses associations between specific cancers and factors like infections, radiation, chemicals, diet, obesity and geography.

1. Cancer Epidemiology II
Professor Tarek Tawfik Amin
amin55@myway.com

3. The Major Cancers
Lung (ICD-10 C33 and C34)
Breast (female, C50)
Colon/rectum (C18-C20)
Stomach (C16)
Prostate (C61)
Liver (C22)
Cervix uteri (C53)
Esophagus (C15)

5. Percentage of Cancer Deaths Attributed
to Various Factors (Doll R and Peto R, JNCI, 1981)
Tobacco Use: 30% (25%-40%)
Diet: 35% (10%-70%)
Infection: 10%? (1%-?)
Reproductive & Sexual Behavior: 7% (1%-
13%)
Occupation: 4%
(<2%-8%)
Alcohol: 3%
(2%-4%)
Geophysical factors (natural radiation): 3% (2-
4%)
Pollution: 2%
(<1% – 5%)
Food additive: <1% (-

6. Harvard Center for Cancer
Prevention (www.hsph.harvard.edu/cancer)
Tobacco: 30%
Diet in adult life, including obesity: 30%
Sedentary lifestyle: 5%
Infectious agents: 5%
Defects in single genes that run in family: 5-10%

7. Chemical/environmental carcinogens
Smoking and lung cancer
Sun exposure and squamous cell
carcinoma of skin
Asbestos exposure and lung
cancer
Smoked food risk with
nitrosamines and adenocarcinoma
of the stomach
Alcohol drinking and squamous

8. Radiation
Exposure to ultraviolet
radiation (in the form of
sunlight) and squamous cell
carcinoma of skin
Ionizing radiation is related to
skin cancer and leukemia in
radiologist

9. Viral factors
HPV (human papilloma virus)
and Cervix cancer
EBV(Epstein-Barr virus) and
Nasopharyngeal cancer,
Burkitt’s lymphoma
HBV (hepatitis B virus) and
hepatocellular carcinoma

10. Geographical risk

11. Table 2.5 part 1 of 2Table 2.5 part 1 of 2 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007)

12. Specific Cancer Incidence and
Migratory Patterns:
Cancers and Environmental Effects

13. One canOne can
distinguishdistinguish
genetic fromgenetic from
environmentalenvironmental
and culturaland cultural
features infeatures in
cancercancer
causation bycausation by
analyzinganalyzing
populationspopulations
with similarwith similar
geneticgenetic
backgroundsbackgrounds
living inliving in
differentdifferent
environments.environments.

14. Epidemiological Datacan also sometimesprovide
cluesabout thebiological mechanismsunderlying
certain typesof cancers.
Malignant Melanoma(Solar radiation exposure)
Burkitt’sLymphoma(Co-infection with virus
transmitted by mosquitoesalso transmitting
malaria)

15. Cancer Incidenceand Changesin GeneExpression:
Reciprocal Translocation
- 9 to 22 Reciprocal
Translocation: Chronic
Myelogenous Leukemia (CML)
- 8 to 14 Reciprocal
Translocation: Burkitts
Lymphoma

16. oReciprocal translocation between
chromosomes 9 and 22 produces fusion
of a cancer-inducing gene, the abelson or
abl gene with information on another
chromosome.
oThis chromosome fusion is expressed as
a fusion protein involving the abl gene
product.
oThis miss-expressed fusion protein drives
cell division in leucocytes leading to
chronic myelogenous leukemia.

17. 
Figure 4.13aFigure 4.13a The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007) p. 109p. 109
Reciprocal Translocation (8 to 14) in Burkitt’s LymphomaReciprocal Translocation (8 to 14) in Burkitt’s Lymphoma

18. Figure 4.12Figure 4.12 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007)
Incidence of Burkitt’s Lymphoma in Relation to Infectious Disease Etiology:Incidence of Burkitt’s Lymphoma in Relation to Infectious Disease Etiology:
Aedes simpsoni mosquito transmission vector for malariaAedes simpsoni mosquito transmission vector for malaria
and Epstein Barr Virus co-infectionand Epstein Barr Virus co-infection

19. Epidemiology of Cancer Based on AgeEpidemiology of Cancer Based on Age

20. AgeEffctAgeEffct
IncidenceIncidence

21. Incidence of Various Kinds of Cancers in Men and Women as a Function ofIncidence of Various Kinds of Cancers in Men and Women as a Function of
AgeAge

22. Environmental and Occupational
Cancers
Effects from Nuclear Plant Melt-Down

24. WorkCxWorkCx

25. Table 2.7Table 2.7 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007)

26. Journal of the National CancerJournal of the National Cancer
Institute, July, 1996Institute, July, 1996
Chernobyl nuclearChernobyl nuclear
power-plant melt-down,power-plant melt-down,
April 1986April 1986
Environmental radiation
from the Chernobyl Nuclear
Plant
Melt-down produced a
marked increase in Thyroid
cancers in children with a
delay of about five years.
Fortunately, thyroid cancers
can be managed fairly
successfully and respond
to treatment. This, of course,
presupposes that modern
treatment is available to the
children.
This supposition may not be
correct in some, or even in
many cases.

27. Cultural Associations and Specific
Cancers

28. Journal of the National Cancer InstituteJournal of the National Cancer Institute
October, 1996October, 1996
A specific histological type of
cancer, such as stomach cancer, can
have markedly different incidence
rates within different
ethnic/cultural groups within a
larger society.
This points to cultural and
possibly to genetic differences that
may contribute to the differences in
incidence rate. In the case of
stomach cancer in different
cultural/ethnic groups within the
U.S., one contributing factor has
been related to differences in
cooking practices, including the
use of charcoal in cooking.
However, recent evidence
concerning endemic infections with
different types of Helicobacter
Pylori that resides in the stomach in
large numbers of people around the
world suggests that there may be
interactions between strains of H.
Pylori and the genetic backgrounds
of individuals that affect the risk
of
developing stomach and
esophageal cancers.

30. 0
1000
2000
3000
4000
5000
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
YEAR
NumberofCigarettes
Adult Per Capita Cigarette Consumption and Major Smoking and Health Events –
United States, 1900-2001
Source: United States Department of Agriculture
End of WW II
1st
Smoking-Cancer
Concern
Fairness Doctrine
Messages on TV
and Radio
Non-Smokers
Rights Movement
Begins
Federal Cigarette
Tax Doubles
Surgeon
General’s
Report on ETS
1st
Surgeon
General’s
Report
1st
World Conference
on Smoking and Health
Broadcast
Ad Ban
1st
Great American
Smoke-out
OTC Nicotine
Medications
Master
Settlement
Agreement
Great Depression

31. Tobacco Use in the US, 1900-2005
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
1900
1905
1910
1915
1920
1925
1930
1935
1940
1945
1950
1955
1960
1965
1970
1975
1980
1985
1990
1995
2000
2005
Year
PerCapitaCigaretteConsumption
0
10
20
30
40
50
60
70
80
90
100
Age-AdjustedLungCancerDeath
Rates*
*Age-adjusted to 2000 US standard population.
Source: Death rates: US Mortality Data, 1960-2005, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control
and Prevention, 2006. Cigarette consumption: US Department of Agriculture, 1900-2007.
Per capita cigarettePer capita cigarette
consumptionconsumption
Male lung cancerMale lung cancer
death ratedeath rate
Female lungFemale lung
cancer death ratecancer death rate

32. Men
Women
0
10
20
30
40
50
60
1955 1960 1965 1970 1975 1980 1985 1990 1995 2000
YEAR
%CURRENTSMOKERS
Trends in cigarette smoking* among adults aged >18 years, by sex - United States,
1955-2002
Source: 1955 Current Population Survey; 1965-2002 National Health Interview Survey; 2002 estimates for first quarter only
*Before 1992, current smokers were defined as persons who reported having smoked >100 cigarettes and who currently smoked. Since 1992, current smokers were
defined as persons who reported having smoked >100 cigarettes during their lifetime and who reported now smoking every day or some days.
24.5%
18.8%

34. Smoking and Other Cancers
Head and neck cancers (oral, laryngeal and
pharyngeal cancers)
Esophageal cancer
Stomach cancer
Pancreatic Cancer
Bladder cancer
Cervical cancer
Liver cancer

36. Environmental Tobacco Smoke
3,000 nonsmoking Americans die of lung cancer
300,000 children suffer from lower respiratory tract
infections.

38. Obesity and Cancer

40. Obesity, globally
International Association for the Study of
Obesity estimated in 2007 ~40-50% of men
and 25%-35% of women in EU were overweight
(25-29.9 kg/m2
)
Additional 15-25% of men and women were
obese.
WHO’s in 2005:
Globally, ~ 1.6 billion adults (age 15+) were
overweight;
at least 400 million adults were obese.
Projects that by 2015, approximately 2.3 billion
adults will be overweight and more than 700
million will be obese.
At least 20 million children under the age of 5
years are overweight globally in 2005.
Not just a problem in high income countries

41. BMI and Mortality
ProspectiveStudiesCollaboration,
Lancet,2009

43. Renehan,2008

45. van Kruijsdijk RCM C, CEBP, 2009
 Potential
pathways
linking obesity
with cancer

46. IGF and Insulin pathway
Calle EE, Kaaks R. Nature, 2004

51. Breast cancer, overview
Most common cancer
among females
192,370 estimated newly
incident female cases,
2009
40,170 estimated female
deaths, 2009
Survival rate by stage
~96% among localized
~84% for regional
~27% for distant
 African-American women
younger than 50 years of
age have a higher age-
specific incidence than
White women
Risk Factors
Age
Genetics
Race
Hormones
Nulliparity, late age of
parity, early menarche.
Obesity
Benign breast disease
Diet
Alcohol
Smoking?
Gale Model
http://www.cancer.gov/bcris
ktool/

52. Renehan, 2008

53. Breast Cancer and Obesity summary
In general, BMI and body weight is positively
associated with postmenopausal breast cancer and
inversely associated with premenopausal breast
cancer
Weight gain has also been associated with greater
risk of post-menopausal breast cancer.
This effect may be modified by HRT use.
Implicated pathways include:
Estrogen
IGF-1
Inverse relationship found in premenopausal
women may be a result of lower circulating sex
steroid hormones.

54. Colon Cancer, overview
Third most common
cancer among men and
women
106,100 estimated cases for
2009
49,920 estimated deaths
5-year survival rate:
90% localized
68% regional
11% distant
African Americans and
Ashkenazi Jews have one
of the highest incidences
Risk factors
Age
Colon polyps
Genetics
Race/ethnicity
History of bowel disease
Obesity
Diet
Alcohol
Smoking
Type 2 Diabetes

55. Obesity and colorectal cancers, summary
In 2002-03 IARC concluded there is sufficient
evidence that obesity is associated with an increased
risk in colo-rectal cancer.
This relationship is stronger among men than
women.
Possibly because body weight and fat distribution
differs between men and women.
Evidence in rectal cancer is inconclusive.
Potential pathways:
Hyperinsulemia
IGF-1
Adipokines and hormones.

56. Prostate Cancer, overview
Most common cancer
among men.
192,280 estimated cases for
2009
27,360 estimated deaths
for 2009
Average 5 year survival
rate:
~over 99% localized and
regional
~32% distant
African-American men are
also more likely to be
diagnosed at an advanced
stage
Risk Factors
Age
Lifetime probability of
prostate cancer 1 in 6
Race
Geographical region
Family History
Genetics (8q24)
Diet?
Obesity?
Infection?
Smoking?

57. Infections-Associated Malignancies

59. Major Infection-Associated Malignancies
In 2002, 17.8% of the global cancer burden (1.9 million
cases) were infection-attributable
Malignancy (infection)
Stomach cancer (Helicobactor pylori)
Cervical cancer (human papilloma virus)
Liver cancer (hepatitis B and C viruses)
Burkitt’s lymphoma and nasopharyngeal cancer (Epstein-
Barr virus)
Kaposi sarcoma and Non-Hodgkin lymphoma (HIV/HHV-8)
Bladder and colon cancer (schistosomiasis)
Adult T-cell leukemia/lymphoma (human T-cell
lymphotropic virus type I)

60. Mechanisms
Chronic Inflammation and Carcinogenesis
Chronic host-pathogen interaction
Immunosuppression
Chronic inflammation
Oxidative Stress
DNA damage and mutations
Cell injury
Cell division
Infection inducing Cell proliferation
Production of Oncogenic Proteins
Genomic Instability from Viral Genomic Integration

61. Cancers attributable to infections worldwide, 2002
Source: Parkin, 2006Source: Parkin, 2006

62. Alcohol

63. Possible Mechanisms How Alcohol Intake Increase Cancer Risk According to Blot et al (1992)
1. Contain congeners and other contaminants that may be
carcinogenic
2. Generated metabolites that are carcinogenic to humans
3. Act as solvent, increasing penetration of other
carcinogens into target tissue
4. Reduce intake and bioavailability of nutrition
5. Inhibit the detoxification of carcinogenic compounds
6. Catalyze the metabolic activation of some compounds
into carcinogens
7. Affect hormonal status
8. Increase cellular exposure to oxidants
9. Suppress immune function
6363

64. Particulate matter

66. Polluted Water

70. 
S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84

71. Known risk factors
Smoking causes most cancers in smokers.
Among non-smokers, most cancers are of unknown
cause.
Infection causes most cancers in the lowest-income
countries.

72. Avoidable Known Cancer Risks USA

73. Proven Cancer Prevention Strategies:
Compelling non-RCT Evidence
Risk Factor Avoidance
Smoking prevention/cessation counseling
Worker exposure reduction (asbestos, etc.)
Immunization
Hepatitis B
HPV
Screening
Cervical PAP testing

74. Proven Cancer Prevention
Strategies: RCT Evidence
Screening
Mammography with Clinical Breast Exam
Fecal Occult Blood Test (colorectal cancer)

75. BRIDGING THE GAP BETWEEN CANCER TREATMENT AND PREVENTION
(William WN, et al, Nat Rev Drug Discov. 2009 Mar;8(3):213-25.)

76. Widely-Accepted Prevention Strategies
Insufficient or Negative Evidence
Oral cancer screening examination
PSA testing for prostate cancer
Lung cancer screening with CT or X ray
Dietary change: More vegetables and fruits
Dietary change: Less fat
Dietary antioxidant supplements
Weight loss and exercise
Sun avoidance: skin cancer

77. Deaths/year can be
prevented?
Tobacco Control
Screening
Infection Control

78. I- Tobacco-Caused Cancers – 1.15 million deaths
Lung 75% of 1,300,000 deaths
Oropharynx 40% of 320,000 deaths
Other sites 15% of 350,000 deaths

79. II- Screen-detectable cancers – 660,000 deaths
Colorectal 50% of 620,000 deaths
Cervix 90% of 230,000 deaths
Breast 30% of 475,000 deaths

80. III- Infection-related Cancers – 750,000 deaths
Liver (immunization) 40% of 600,000 deaths
Stomach (antibiotics) 60%? of 850,000 deaths
[Cervix (immunization)] 50% of 230,000 deaths]

81. Overall yield of cancer prevention::
Tobacco programs 1,115,000 at low cost
Infection Control 750,000 at low/moderate cost
Screening 660,000 at low/very high cost
Total deaths preventable: about 2.5 Million of
the 7.5 million deaths/year from cancer
worldwide

82. Thank you