gy

i o lo
e m
CANCER EPIDEMIOLOGY

p id
E
 y
CANCER EPIDEMIOLOGY

lo g
i o
1775
A British surgeon first described the likelihood

m
of occurrence of (professional) scrotal cancer

e
in chimney sweeps

p id
Sir Percivall Pott
(1713-1788)

E
British surgeon
 y
AIMS OF CANCER EPIDEMIOLOGY
 Exploring the etiology
- cancer distribution studies

lo g
i o
- quantification of the risk of association between the

m
exposure and factors of the host

id e
Encouraging insights into carcinogenesis mechanisms

p
Evaluation of the effectiveness of preventive measures

E
Survival Prediction Survey
 Evaluation of the effectiveness of preventive measures

 Researching the survival predictors

LEADING CAUSES OF DEATH IN THE WORLD

gy
lo
18%

o
6% 27%

i
4%

m
8%

e
37%

p id
E
LEADING CAUSES OF DEATH IN THE WORLD BY
GENDER

gy
i o lo
e m
p id
E
LEADING CAUSES OF DEATH IN SERBIA, IN 1997 AND
2007

gy
i o lo
e m
p id
E
 gy
i o l o
World Cancer Declaration

e m
Participants from 139 countries:

p id
• About 11 million people around the world are diagnosed with
a malignant tumor, and

E
•About 7 million people die from cancer every year.
• More than 25 million people live with a cancer diagnosis,
•By 2020, there will be 16 million newly diagnosed and 10 million
deaths every year
• About 70% will be from underdeveloped countries
 Malignant tumors, world

y
years

g
2008 2030

lo
millions

New cases
i
12.7
o 22.5
Deaths

e m
7.6* 13.5

id
(70% in underdeveloped countries)

E p
Prevalence 29 40
Population 6 billion 8 billion
Global Cancer Burden, WHO & World Bank, 2009.

Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds (2007),
Cancer Incidence in Five Continents, Vol. IX, IARC Scientific Publications No. 160, Lyon, IARC.
TEN LEADING MALIGNANT TUMORS IN THE WORLD IN 2012, IN TERMS OF NEW CASES
AND DEATHS (MEASURED BY STANDARDIZED RATES* OF INCIDENCE AND MORTALITY PER
100,000 INDIVIDUALS)

gy
12,9
Rak dojke

lo
43,1
Rak prostate 7,8
30,7
19,7

o
Rak pluća
23,1

i
8,4
Rak kolorektuma 17,2
6,8
Rak grlića materice

m
14
8,9
Rak želuca 12,1

e
Rak jetre 9,5
10,1

id
3,8 Mortalitet/100.000
Rak jajnika 6,1
Rak jednjaka 5 Incidencija/100.000

p
5,9
Rak bešike 1,9
5,3

E
2,5
Ne-Hodginov limfom 5,1
3,4
Leukemija 4,7
1,8
Rak bubrega 4,4
Rak pankreasa 4,1
4,2
0 10 20 30 40 50

*according to the world population GLOBOCAN, 2012.

 DISTRIBUTION OF THE MOST COMMON

y
MALIGNANT TUMORS IN THE MALE POPULATION

lo g
i o
e m
p id
E
 DISTRIBUTION OF THE MOST COMMON

y
MALIGNANT TUMORS IN THE FEMALE POPULATION

lo g
i o
e m
p id
E
 gy
i olo
e m
p id
E
 gy
i olo
e m
p id
E
 gy
i olo
e m
p id
E
 gy
i olo
e m
p id
E
 Burden of specific diseases (DALY per 1000 individuals)
by gender, Serbia, 2000

y
Ischaemic heart disease

g
Cerebrovascular disease Lung cancer
6.66 DALY/1000 (8.1%)

lo
Lung cancer

Unipolar depressive disorders Colorectal cancer

o
Diabetes mellitus 2.85 DALY/1000 (3.5%)

i
Road - traffic accidents
Breast cancer
2.76 DALY/1000 (3.4%)

m
Self - inflicted injuries

Colon and rectal cancer Stomach cancer

e
Breast cancer 1.84 DALY/1000 (2.2%) Males

id
Stomach cancer Females

Nephritis and nephrosis

Cervical cancer

p
0.98 DALY/1000 (1.2%)
Birth asphyxia and trauma

E
Asthma

Cervix uteri cancer

Overall burden:
Low birth weight
82 DALY per 1000 individuals
Tuberculosis
95 DALY per 1000 men
Hearing and vision loss
71 DALY per 1000 women
HIV / AIDS

0 5 10 15 20 25 30
DALYs per 1,000 population
INCIDENCE OF MALIGNANT TUMORS AND ECONOMIC

y
DEVELOPMENT OF COUNTRIES

lo g
i o
e m
p id
E
PROJECTIONS OF INCIDENT CANCER CASES

gy
i o lo
e m
p id
E
 gy
i o lo
e m
p id
E
LUNG CANCER EPIDEMIOLOGY
LUNG CANCER

gy
lo
 The most common cancer localization throughout the world

o
 1.8 million incident cases in 2012 (13% of all cancers)

m i
Leading cause of death: 1.5 million deaths every year

 In the USA (2016):

id e
p
- 224,390 with Dg of Lung Ca (117,920 men, 106,470 women)

E
- 158,080 † (26.5% of all cancer-related deaths);
- The number of deaths is larger than the number of deaths from
colon, breast and prostate Ca combined
- Since 1987, more women die from lung Ca than from breast Ca
2016 ESTIMATED US CANCER CASES*

y
Men Women

g
841,390 843,820

lo
Prostate 21% 29% Breast

io
Lung & bronchus 14% 13% Lung & bronchus
Colon & rectum 8% 8% Colon & rectum

m
Urinary bladder 7% 7% Uterine corpus

e
Melanoma of skin 6% 6% Thyroid

d
Non-Hodgkin 5% 4% Non-Hodgkin

i
lymphoma lymphoma

p
Kidney & renal pelvis 5% 3% Melanoma of skin

E
Oral cavity 4% 3% Leukmia
Leukemia 4% 3% Kidney & renal pelvis
Liver 3% 3% Pancreas
All Other Sites 23% 22% All Other Sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2016.
2009 ESTIMATED US CANCER DEATHS*

y
Men Women

g
314,290 281,400

lo
Lung & bronchus 27% 26% Lung & bronchus

io
Prostate 8% 14% Breast
Colon & rectum 8% 8% Colon & rectum

m
Pancreas 7% 7% Pancreas

e
Liver 6% 5% Ovary

d
Leukemia 4% 4% Uterine corpus

i
Oesophagus 4% 4% Leukemia

p
Urinary bladder 4% 3% Liver

E
Non-Hodgkin ly 4% 3% Non-Hodgkin ly
Brain & oth.nerv.sy. 4% 2% Brain & oth.nerv.sy.
All Other Sites 24% 24% All Other Sites

ONS=Other nervous system.

Source: American Cancer Society, 2016.
LUNG CANCER (C33-C34): ESTIMATED AGE-STANDARDIZED RATES (WORLD)
PER 100,000, WORLD REGIONS, 2012

gy
i o lo
e m
p id
E
 Lung Cancer (C33-C34): European age-standardized incidence
rates by sex, area and country per 100,000, EU-27 Countries, 2012

gy
i olo
e m
p id
E
Source: Ferlaz J, et al. Cancer incidence and
mortality patterns in Europe: Estimates
for 40 countries in 2012. Eur J Cancer.
2013;49(6):1374-403.
LUNG CANCER TYPES

gy
lo
3%

i o
15% Small Cell
15%

m
Squamous cell

id e
Adenocarcinoma

p
Large-cell
30%

E
(undifferentiated)
Carcinoid
40%

Data from American Cancer Society

AGE
 Incidence and

gy
lo
mortality rates start

o
growing between 45

i
and 54 years of age
and then grow

m
progressively after

e
75

id
 Median age at the

p
moment of diagnosis
= 70.07

E
 Median age at the
moment of death
=71.07
GENDER

gy
lo
 Men have a higher risk of developing lung cancer during
their lifetime than women:

i o
m
7.8% vs. 5.8%

id e
The difference is even larger in the developing countries

p
where the prevalence of female smokers is lower

E
TREND

gy
i olo
e m
p id
E
 gy
i olo
e m
p id
E
 gy
i olo
e m
p id
E
CANCER REGISTER OF CENTRAL SERBIA

gy
i o lo
e m
p id
E
CANCER REGISTER OF CENTRAL SERBIA

gy
i o lo
e m
p id
E
CANCER REGISTER OF CENTRAL SERBIA

gy
Leading localizations of malignant tumors in terms of new cases in men, Central Serbia, 2013

i o lo
e m
p id
E
CANCER REGISTER OF CENTRAL SERBIA

gy
Leading localizations of malignant tumors in terms of deaths in men, Central Serbia, 2013

i o lo
e m
p id
E
 CANCER REGISTER OF CENTRAL SERBIA

gy
Leading localizations of malignant tumors in terms of new cases in women, Central Serbia, 2013

i o lo
e m
p id
E
CANCER REGISTER OF CENTRAL SERBIA

gy
Leading localizations of malignant tumors in terms of deaths in women, Central Serbia, 2013

lo
.

i o
e m
p id
E
 CANCER REGISTER OF CENTRAL SERBIA

gy
Incidence rates of cancer per 100,000 individuals by leading localisations and districts, men, Central Serbia,

lo
2013

i o
e m
p id
E
 CANCER REGISTER OF CENTRAL SERBIA

gy
Incidence rates of cancer per 100,000 individuals by leading localisations and districts, women, Central

lo
Serbia, 2013

i o
e m
p id
E
 y
RISK FACTORS
 Smoking

lo g
o
 Radon

i
 Other chemical substances (asbestos, arsen, diesel fuel)

m
 Heritage

id e
 Radiotherapy of the chest

 Nutrition

p
 Genetic factors (EGFR or KRAS mutations)

E
 gy
i olo
e m
p id
E
 y
SMOKING

lo g
In the USA, cigarette smoking is the cause of 90% of lung

i o
cancer

m
 Pipe or cigar smoking also increases the risk

e
 Over 7,000 chemical substances in tobacco smoke – at

id
least 70 are confirmed to cause cancer in men and
animals

E p
 15-30% higher risk of lung cancer in smokers when
compared to non-smokers
 Even smoking a couple of cigarettes per day, or smoking
occassionaly increases the risk
 Passive smoking is also a risk
 gy
i o lo
e m
p id
E
BREAST CANCER EPIDEMIOLOGY
 y
BREAST CANCER – A GLOBAL PHENOMENON

lo g
o
Most commonly diagnosed

i
malignant tumor in the female

m
population around the world.

year 2012
id e
E p
1,700,000 new cases of the disease

 522,000 deaths

Source: Ferlay J et al. (2013). GL OBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet].
Lyon, France: International Agency for Research on Cancer
BREAST CANCER – PROPORTIONS IN THE

y
STRUCTURE IN TERMS OF NEW CASES AND DEATHS

lo g
i o
e m
p id
E
Leading localisations in terms of new cases and deaths from
malignant tumors in females, Serbia, 2011

gy
New cases (%) Deaths (%)

lo
Breast (C50) – 25.7 18.5 - Breast (C50)

o
Cervix uteri (C53) – 6.9 14.1 - Lung/bronchus (C34)

i
Colon/rectum (C18-C20) – 8.1 11.3 - Colon / rectum (C18-C20)

m
Lung/bronchus (C34) – 7.8 5.5 – Cervix uteri (C53)

e
Endometrial (C54) – 5.4 5.5 - Pancreas (C25)

id
Ovarian (C56) – 2.4 4.4 - Stomach (16)

p
Stomach (C16) – 2.6 4.5 - Ovarian (C56)

E
Bladder (C67) – 2.0 3.3 - Liver (C22)
Pancreas (C25) – 2.5 3.8 - Brain (C71)
Brain (C71) – 2.6 2.7 – Endometrial (C54)
Leukemia (C91-C95) – 1.9 2.7 – Leukemia (C91-C95)

Other localizations – 32.1 23.7 - Other localizations

 BREAST CANCER– WHOLE LIFE RISK

gy
i o lo
e m
p id
E
Cumulative chance of developing the disease in the population of women is
12.4%, meaning that every 8th woman suffers from this disease during
her lifetime !!!!!!
Breast cancer incidence

gy
i o lo
e m
p id
E
GLOBOCAN 2008, International Agency for Research on Cancer
 BREAST CANCER MORTALITY

gy
i o lo
e m
p id
E
GLOBOCAN 2008, International Agency for Research on Cancer
 BREAST CANCER IN SERBIA

gy
lo
↑ incidence rates

o
↑ mortality rates

m i
id e
Around:

E p
4000 new cases
1600 deaths
every year

In Serbia, every 12th woman suffers from breast cancer

BREAST CANCER – INCIDENCE AND MORTALITY
Year Incidence/ Mortality/

y
100,000 100,000
1999 56.9 21.8

lo g
2000 60.0 20.1

2001 61.7 20.2

i o
2002 64.1 18.7

2003 60.4 20.9

m
2004 57.9 20.5

id e
2005 56.1 20.9

2006 59.4 19.1

p
2007 60.2 20.0

E
2008 61.1 20.3

2009 71.5 20.3

2010 67.8 21.4

2011 69.7 19.9

2012 68.3 20.2

2013 50.5 19.2

 y
AVERAGE INCIDENCE RATES IN BELGRADE

lo g
i o
e m
id
Period from 1999 to 2010:

p
84.40/100,000

E
 INCIDENCE RATES OF BREAST CANCER IN EUROPE

y
Standardized incidence rates per 100,000 women, 2008

lo g
Belgium
Denmark
109.2
101.1

i o
France 99.7
...

m
Croatia 64.0

e
Slovenia 64.9

id
Serbia 61.1
Bulgaria 55.5

p
Macedonia 53.5

E
Romania 45.4
…
Moldavia 38.7
B&H 36.5

Source: Globocan 2008

 TREND OF GROWTH OF INCIDENCE OF BREAST CANCER

gy
3.1%

i o lo
e m
p id
E
Results of a sistematic review of incidence rates of breast cancer in 187 countries
(including Serbia) in the period from 1980 to 2010 have showed a continued growth
of risk for developing this disease which, in the observed time period, was 3.1% per
year!!!
 Breast cancer – incidence trend
Standardized incidence rates per 100,000 women, 2008

gy
lo
2005

i o
e m
p id
1980
E
Source: European HFA Database, 2008
 BREAST CANCER – INCIDENCE TREND

y
Standardized incidence rates per 100,000 women, 2012

lo g
i o
e m
p id
E
Source: GLOBOCAN 2012
 BREAST CANCER – FUTURE ESTIMATES

gy
i o lo
e m
p id
E
If the continued trend of growth of incidence rates of breast cancer continues,
in 15 years 3 million new cases per year can be expected!!!!

Source: Li. CI. Breast Cancer Epidemiology, 2010

 BREAST CANCER – MORTALITY TREND
Standardized mortality rates per 100,000 women, 2012

gy
i o lo
e m
p id
E
The organized screening for early detection of breast cancer has led to a decrease
of the mortality of this disease in most countries!!!

Source: GLOBOCAN 2012

Ten year survival relative to BC stage at the moment
of diagnosis

97%

gy
94%

lo
100
Localized
90

o
79% disease

i
80
66%
70

m
Regionally
60 disseminated

e
50

id
40

p
30 24%

E
20 13%
Distant
10 metastasis
0
0 1 2 3 4 5 6 7 8 9 10 god.
Godine
 Breast cancer – ratio of the number of new cases in women and
their 5-year survival in the different parts of the world

gy
i o lo
USA (83–88%)

m
Europe

5-year survival
(60–83%)

id
Developing countries

p
(45–72%)

E Number of new cases (women)

Source: IARC Sci Publ 2008;145:135–73

 y
RISK FACTORS FOR DEVELOPING BREAST CANCER

lo g
i o
e m
p id
E
 y
WE ARE FAMILIAR WITH THE RISK FACTORS

g
FOR BREAST CANCER FOR A LONG TIME...

 1850 – family history

 1920 – birth-related risk factors

i o lo
m
 Lane-Claypon, 1926, case-control study

e
 1950 - menopause

id
 1970 – oral contraceptives, hormones after menopause, diet,

p
physical activity, obesity, endogenous hormones, SERMs

E
 Risk factors unsusceptible to change –
non-modifiable risk factors

gy
lo
Age

i o
Gender Reproductive
-all women are at risk factors
Genetic factors

e m
id
Menstrual

pRace cycles

E Positive
breast cancer
anamnesis
Childhood chest
X-rays Breast
structure
Risk factors susceptible to change – modifiable risk
factors

gy
lo
Obesity

o
Not breast-

i
All women are
at risk feeding

m
Physical

e
inactivity

id
Not giving

p
Diet birth

E
(animal fat?)
Hormonal
therapy Oral
Alcohol in menopause contraceptives?
GENETIC PREDISPOSITION FOR DEVELOPING BREAST

y
CANCER???

lo g
i o
e m
p id
E
 GENETIC PREDISPOSITION FOR DEVELOPING BREAST
CANCER???

gy
i o lo
m
15%-20%

id e
E p
5%–10%

Sporadic disease
Family cluster
Hereditary disease
Genetic predisposition for developing breast

y
cancer???

lo
Other

g
o
16%

m i
e
Hereditary
Cancer

id
10%

p
BRCA2 BRCA1

E
Others 32% 52%
90%

King, Rowell, Love, 1993; Ford, Easton, Stratton, et al, 1998

 MUTATIONS OF BRCA1 I BRCA2 GENES (BRCA: BREAST
CANCER GENE)

gy
BRCA1 (17q21) in 1994

i olo
m
BRCA2 (13q12) in 1995

Frequency

id e
p
► 1/500-1/800 (0.2%) in the general population

E
► 1/50 (2%) in the population of Ashkenazi Jews
► 5-10% in women with breast cancer

Source: 1. Miki i sar. Science 266: 66-71, 1994.

2. Wooster i sar. Nature 378: 789-792, 1995.
 BRCA1/2 GENES – AUTOSOMAL DOMINANT INHERITANCE

gy
i o lo
e m
p id
E
The offspring of the carriers of the BRCA1/2 genes mutation have 50% chance
to inherit a mutated gene allele from one of the parents.
 WHAT IS THE RISK FOR DEVELOPING

gy
BREAST CANCER IN THE CARRIERS OF

lo
THE OF BRCA1/2 MUTATIONS???

i o
e m
p id
E
Risk for developing breast cancer, aged 65, relative
to the BRCA gene mutation

gy
100 10

lo
90 9

o
80 8

i
70 7

e m
60 6

id
50 5

p
40 4

E
30 3

20 2

10 1

0 0
Mutated BRCA1/2 Normal BRCA1/2
BRCA MUTATIONS – RISK FOR DEVELOPING BREAST

y
CANCER

lo g
o
Age BRCA1+ BRCA2+

30

m i
3.2 % 4,6 %

id e
40 19.1 % 12 %

p
50 50.8 % 46 %

E
60 54.2 % 61 %

70 85 % 86 %
BRCA1 – WHOLE LIFE RISK FOR CANCER

gy
lo
Breast cancer 50%-85%

i o
(often with early onset, before 40th year)

e m
Second breast cancer 40%-60%

id
Ovarian cancer 15%-45%

E p
BRCA2 – WHOLE LIFE RISK FOR CANCER

gy
lo
Breast cancer

o
(50%-85%)

i
Breast cancer

m
(6%)

id e
Ovarian cancer

p
(10%-20%)

E Larynx, prostate, pancreas cancer?

 INDICATIONS FOR GENETIC SCREENING

y
,,HIGH -RISK-FAMILIES”

Women that have:

lo g
o
• A first-degree relative with billateral BC

i
• Two first-degree relatives that had BC, and at least one was

m
diagnozed before 50 years of age

e
• Three and more first or second-degree relatives with BC, no

id
matter the age on diagnosis
• A first or second-degree member of the family with BC and

p
ovarian cancer

E
• A male member of the family with BC
• Two or more first or second degree relatives with OC, no
matter the age on diagnosis
• A member of the family with BC or OC which has a confirmed
BRCA mutation
TO TEST OR NOT TO TEST?

gy
i o lo
e m
p id
E
CARRIERS OF BRCA1/2 MUTATIONS!?

gy
lo
► Monthly manual breast examinations after 18 years of age

i o
► Mamography once per year after 25 years of age

m
► Ifthe carrier of BRCA ½ mutations has a positive family history

e
for ovarian cancer

id
 Ginecological examinations, trans-vaginal U/S, +/- CA-125 1-2 times

p
per year, starting with 25 or 30 years of age

E
► Preventive interventions:
-chemoprevention
-profilactic surgery
Carriers of BRCA1/2 mutations!?

gy
o lo
► Chemoprevention

i
 Tamoxifen reduces the risk in BRCA2 carriers, (BRCA1 ????)

m
► Profilactic bilateral mastectomy

id e
 ~90% reduction in risk
► Profilactic bilateral oophorectomy

p
 ~up to 95% reduction of risk for ovarian cancer

E
 ~50% reduction of risk for breast cancer
RISK FACTORS FOR BREAST CANCER

y
RELATIVE RISK

g
> 4.0 2.1 – 4.0 1.1 – 2.0

lo
Age >65 years Higher values of endogenous estrogene and/or Alcohol
testosterone

io
Genetic mutations Being exposed to higher dosages of chest Physical inactivity
(BRCA1 and/or BRCA2) radiation

m
Atypical hyperplasia Postmenopausal higher bone density Obesity
of breast tissue

e
Positive personal history Positive family history of breast cancer Early menarche (< 12 years)
of breast cancer Late menopause (> 55 years)

id
Women who didn’t give birth
Women who didn’t breastfeed

p
Longterm hormone therapy
(estrogene and/or progestin)

E
Positive personal history of endometrial,
ovarian or colorectal cancer
Higher socio-economic status

Risk factors that have been shown to have the highest association with
the development of breast cancer belong to the non-modifiable risk
factors group!!
However.....

gy
i olo
e m
p id
E
WORLD CANCER DECLARATION
11 GOALS

gy
i o lo
e m
p id
E