Download epidemiology of cancer

EPIDEMIOLOGY OF CANCER
and
GENERAL RISK FACTORS OF CANCER
Hanggoro Tri Rinonce, MD, PhD
Department of Anatomical Pathology
Faculty of Medicine, Gadjah Mada University
INTRODUCTION
• Cancer epidemiology  knowledge about the
origin of cancer.
– Cigarette smoking  lung cancer
– Dietary fat and fiber content  colon cancer
• Causes of cancer?  epidemiology studies
– Environmental factor
– Racial (hereditary) factor
– Cultural factor
• Preneoplastic disorders  clues to the
pathogenesis of cancer
CANCER INCIDENCE
• US, 2011
– ± 1.5 million new cancer cases
– 569,000 people died of cancer
• Over several decades, the death rates for many forms
of cancer have changed.
– Men: Death rate for lung cancer  
– Women:
• Overall death rate   death rates for cancers of the uterine
cervix, stomach, and large bowel .
• Lung cancer 
•  death rate from cervical cancer  use of cytologic smear
• Human papillomavirus (HPV) vaccine  eliminate cervical cancer?
•  death rates for stomach cencer   exposure to dietary
carcinogens
Cancer incidence and mortality by site and sex (US, 2010)
Geographic and Environmental
Variables
• Environmental factors are the predominant cause of the
most common sporadic cancers.
– Geographic differences in death rates from specific forms of
cancer.
• Death rates from breast cancer are about four to five times higher in
the United States and Europe than in Japan.
• Death rate for stomach carcinoma in men and women is about seven
times higher in Japan than in the United States.
• Liver cell carcinoma is relatively infrequent in the United States but is
the most lethal cancer among many African populations.
• Nearly all the evidence indicates that these geographic
differences are environmental rather than genetic in origin.
– Nisei (second-generation Japanese living in the United States)
have mortality rates for certain forms of cancer that are
intermediate between those in natives of Japan and in
Americans who have lived in the United States for many
generations.
• Environmental carcinogens
– Ambient environment
– Workplace
– Food
– Personal practices  cigarette smoking and
chronic alcohol consumption
– Sunlight
– In urban settings  asbestos
– Limited to a certain occupation
– Age at first intercourse and the number of sex
partners
Occupational Cancers
AGE
• Cancer  increases with age.
– Most cancer deaths: 55 and 75
• The rising incidence with age ?
– the accumulation of somatic mutations
– the decline in immune competence that accompanies aging
• Cancer causes slightly more than 10% of all deaths among
children younger than 15 years.
• The major lethal cancers in children
–
–
–
–
leukemias
tumors of the central nervous system
Lymphomas
soft tissue and bone sarcomas.
HEREDITY
• Many types of cancer  hereditary
predispositions.
• Hereditary forms of cancer
– Autosomal dominant cancer syndromes
– Autosomal Recessive Syndromes of Defective DNA
Repair
– Familial cancers of uncertain inheritance
Inherited
Predisposition to
Cancer
Autosomal Dominant Cancer
Syndromes
• Retinoblastoma
–
–
–
–
40% are familial
Inherited disabling mutations in a tumor suppressor gene
Carriers of this gene have a 10,000-fold increased risk
Familial retinoblastoma
• Bilateral tumors
• Increased risk of developing a second cancer, particularly osteosarcoma.
• Often ssociated with a specific marker phenotype.
• May be multiple benign tumors in the affected tissue  familial
polyposis of the colon and in multiple endocrine neoplasia .
• Abnormalities in tissue that are not the target of transformation 
Lisch nodules and cafe-au-lait spots in neurofibromatosis type 1.
Autosomal Recessive Syndromes of
Defective DNA Repair
• A group of rare autosomal recessive disorders
is collectively characterized by chromosomal
or DNA instability and high rates of certain
cancers.
• Xeroderma pigmentosum  DNA repair is
defective.
Familial Cancers of Uncertain
Inheritance
• Virtually all the common types of cancers that
occur sporadically have been reported to occur in
familial forms where the pattern of inheritance is
unclear  carcinomas of colon, breast, ovary,
and brain.
• Features that characterize familial cancers
– Early age at onset
– Tumors arising in two or more close relatives of the
index case
– Multiple or bilateral tumors
• Familial cancers are not associated with specific
marker phenotypes.
• What can be said about the influence of heredity in the
large preponderance of malignant tumors?
• There is emerging evidence that the influence of hereditary
factors is subtle and sometimes indirect.
• The genotype may influence the likelihood of developing
environmentally induced cancers.
– Polymorphisms in drug-metabolizing enzymes confer genetic
predisposition to lung cancer in people who smoke cigarettes.
– Genomewide association studies (GWAS) in lung cancer, which
sought to identify common genetic variants that increase risk for
developing cancer, identified variants in a nicotinic acid receptor
as being associated with development of lung cancer.
– These variants were strongly associated with the number of
cigarettes smoked, suggesting that they indirectly increase lung
cancer risk by enhancing the addictiveness of cigarettes.
ACQUIRED PRENEOPLASTIC LESIONS
• In many instances, precursor lesions arise in the setting
of chronic tissue injury or inflammation, which may
increase the likelihood of malignancy by stimulating
continuing regenerative proliferation or by exposing
cells to byproducts of inflammation, both of which can
lead to somatic mutations.
• Molecular analyses have shown that many precursor
lesions possess some of the genetic lesions found in
their associated cancers.
• Precursor lesions are important to recognize  their
removal or reversal may prevent the development of a
cancer.
• Precursor lesions:
– Squamous metaplasia and dysplasia of the bronchial
mucosa, seen in habitual smokers  lung cancer
– Endometrial hyperplasia and dysplasia (in women
with unopposed estrogenic stimulation) 
endometrial carcinoma
– Leukoplakia of the oral cavity, vulva, or penis 
squamous cell carcinoma
– Villous adenomas of the colon  colorectal
carcinoma
• What is the risk of malignant change in a benign
neoplasm?
• Are benign tumors precancerous?
• In general the answer is no, but inevitably there are
exceptions, and perhaps it is better to say that each
type of benign tumor is associated with a particular
level of risk, ranging from high to virtually nonexistent.
– Adenomas of the colon as they enlarge can undergo
malignant transformation in 50% of cases
– Malignant change is extremely rare in leiomyomas of the
uterus.
SUMMARY
• The incidence of cancer varies with age, race, geographic factors,
and genetic backgrounds.
– Cancers are most common at the two extremes of age.
– The geographic variation results mostly from different environmental
exposures.
• Most cancers are sporadic, but some are familial.
– Autosomal dominant  inheritance of a germ line mutation of cancer
suppressor genes
– Autosomal recessive associated with inherited defects in DNA
repair.
• Familial cancers
– Bilateral
– Arise earlier in life
• Some acquired diseases (preneoplastic disorders)  increased risk
for development of cancer.
TOBACCO AS RISK FACTOR
OF
LUNG CARCINOMA
Annual incidence risks of lung cancer per 100,000 people in 2012 ( International Agency for
Research on Cancer)
Estimated causes of lung cancer in
Britain, 2014.
US National Cancer
Institute, Surveillance,
Epidemiology, and End
Results Program Cancer
Statistics Review 1975–
2011
• Smoking-related carcinomas of the lung arise by a stepwise accumulation
of a multitude of genetic abnormalities  transformation of benign
progenitor cells in the lung into neoplastic cells.
• The sequence of molecular changes is not random but follows a
predictable sequence that parallels the histologic progression toward
cancer.
– Inactivation of the putative tumor suppressor genes located on the short arm
of chromosome 3 (3p) is a very early event, whereas TP53 mutations or
activation of the KRAS oncogene occurs relatively late.
• It seems that certain genetic changes, such as loss of chromosomal
material on 3p, can be found even in benign bronchial epithelium of
persons with lung cancer, as well as in the respiratory epithelium of
smokers without lung cancer, suggesting that large areas of the respiratory
mucosa are mutagenized after exposure to carcinogens (“field effect”). On
this fertile soil, those cells that accumulate additional mutations
ultimately develop into cancer.
• About 90% of lung cancers occur in active smokers or those who stopped
recently.
• A nearly linear correlation has been recognized between the frequency of
lung cancer and pack-years of cigarette smoking.
– The increased risk becomes 60 times greater among habitual heavy smokers
(two packs a day for 20 years) than among nonsmokers.
• Since only 11% of heavy smokers develop lung cancer, however, other
predisposing factors must be operative in the pathogenesis of this deadly
disease.
• For reasons not entirely clear, women have a higher susceptibility to
carcinogens in tobacco than men.
• Although cessation of smoking decreases the risk of developing lung
cancer over time, it may never return to baseline levels.
• In fact, genetic changes that predate lung cancer can persist for many
years in the bronchial epithelium of former smokers.
• Passive smoking (proximity to cigarette smokers) increases the risk of
developing lung cancer to approximately twice that of nonsmokers.
• The smoking of pipes and cigars also increases the risk, but only modestly.
Precursor lesions of squamous cell carcinomas that may antedate the appearance of invasive tumor by years. A–C, Some of the earliest (and “mild”) changes in
smoking-damaged respiratory epithelium include goblet cell hyperplasia (A), basal cell (or reserve cell) hyperplasia (B), and squamous metaplasia (C). D, More
ominous changes include the appearance of squamous dysplasia, characterized by the presence of disordered squamous epithelium, with loss of nuclear polarity,
nuclear hyperchromasia, pleomorphism, and mitotic figures. E and F, Squamous dysplasia may, in turn, progress through the stages of mild, moderate, and severe
dysplasia. Carcinoma in situ (CIS) (E) is the stage that immediately precedes invasive squamous carcinoma (F). Apart from the lack of basement membrane disruption
in CIS, the cytologic features of CIS are similar to those in frank carcinoma. Unless treated, CIS eventually progresses to invasive cancer.
Berhentilah merokok sebelum rokok
menghentikanmu 