EPIDEMIOLOGY OF CANCERS

Sudarsa Division of Surgical Oncology, Department of Surgery. School of Medicine University of Udayana Sanglah Hospital Denpasar

Epidemiology is a science, which studying a disease, its distribution and changes of a particular disease in a (risk) population.

Cancer Epidemiology is a science, which studying Cancers, their distribution, changes. differences in a population, and comparing differences among populations, races, etc.

Cancer Epidemiology : GOALS

CAUSATION OF CANCERS (Risk factors, etiology) EFFECTIVE PREVENTION reduce incidence/ morbidity reduce mortality

STUDIES IN CANCER EPIDEMIOLOGY

- MORBIDITY - Prevalence - Incidence - Differences - Data ( pathology/ Autopsy, Hospital, population based registry, Ad-hoc survey/ safari survey) - MORTALITY - Time Trends, interpretations - Differences - Cancer mortality and occupation - Cancer death and other characteristics - etc

WHO PRIORITIES IN CANCER MANAGEMENT

Primary Prevention (Public Education, Political will, vaccination). Secondary Prevention : Early Detection Screening Program (mass or individual) Tertiary Prevention : Prompt Diagnosis & Appropriate Treatment Palliative Management pain management.

STUDY CANCER EPIDEMIOLOGY

- Descriptive Epidemiology. Data obtained from Hospital, pathology. autopsy, safari survey, ad-hoc survey. population based tumor registry. - Analytical Epidemiology Cross Sectional Study Case Control Retrospective Study Prospective Cohort Study

Global Cancer Statistics

GLOBOCAN 2008 (available at http://www. globocan.iarc.fr) 12.7 million cancer cases and 7.6 million cancer deaths. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths.

Number Of New Cancer Cases And Deaths In 2008 For The Ten Leading Cancer Sites By Sex, Worldwide, And By Level Of Economic Development.

CANCERS : World Trends

Dikutip dari Clinical Oncology. Abeloff, 2004.

CANCERS : World Trends

Dikutip dari Clinical Oncology, Abeloff, et al, 2004

Looking at Specific Site CancerWorld Trends

Lung cancer

Colo-Rectal Cancer

Colo-Rectal Cancer : Differences in Migrant Populations

BREAST CANCER

PRECANCER LESIONS BREAST CANCER

RISK FACTORS OF BREAST CANCER.

Breast Cancer in Bali Hospital & Pathology Based

umur

40

30

Frequency

20

10

0 20 - 25 66 - 70 > 70 26 - 30 31 - 35 36 - 40 41 - 45 46 - 50 51 - 55 56 - 60 61 - 65 Th Th Th Th Th Th Th Th Th Th Th

umur

BALI BREAST CANCER ACCORDING TO AGE

std

70

60

50

Frequency

40

30

20

10

0 I IIA IIB IIIA IIIB IIIC IV

std

Bali Breast Cancer Population according to Stage.

BREAST CANCER IN BALI 70 80% were at stage III & IV

No mass screening program No effective individual program. No effective public education No effective professional education Avoidance of surgery. Avoidance of chemotherapy Avoidance of radiation therapy Less risk of choosing alternative medicines. Huge advertisement of traditional medicines/ complimentary medicines.

The Success Role of Epidemiological Study in Cancer :

Cervical Cancer. Etiology (HPV, H.S.V) Prevention/ Primary Lowering the Incidence/ morbidity/ pre-cancer lesions Effective method of early detection/ mass screening method better outcome of treatment. Lowering mortality

CARCINOGENESIS

CANCER CELL. 1. 2. 3. 4. Activation of Oncogenes. Deactivation of Tumor Supressor Genes Defect of DNA Repair Genes. Defect of Apoptosis.

Carcinogen
90 95% cancers sporadic cancers 5 10% familial cancers. Sporadic cancers environment factors 30 40% cancers probably preventable. Material (chemical, radiation, virus, diet) causing cancers carcinogen. Carcinogen could directly causing cancers, or indirectly. Indirect carcinogens (co-carcinogen) have to be metabolized into more active carcinogen.

CARCINOGEN DAMAGE TO DNA chain Gene alteration/ mutation

CO-CARCINOGEN ACTIVATED CARCINOGEN DAMAGE TO DNA Gene alterations/ mutation Damage the DNA or structures surround DNA, That ..if changed would Influence the DNA function transformed cell. Carcinogens cause mutation mutagens

DAMAGE TO DNA (direct or indirect) COULD BE REPAIRED BY DNA REPAIR GENES. OR CELLS COULD BE GEARED INTO CELL CYCLE ARREST. OR APOPTOSIS. If not corrected, cell will replicate, and will change its function.

Etiology of Cancer
Tobacco Cancer Susceptibility syndromes (5-10%) DNA Viruses RNA Viruses Inflammation Chemical Factors Physical Factors Dietary Factors Obesity and Physical Activity

TOBACCO
Cigarette smoking, Kreteks, Bidis, Chewing tobacco, Pan and betel quid. Cigarette smoking causes well over 1 million cancer deaths annually worldwide. Lung cancer is the dominant malignancy caused by smoking. Carcinogens in tobacco products Cigarette, Cigar, Pipe, Secondhand/Forced smoking..

World Smoking Prevalence by Gender

Lung Cancer Death Rates And Per Capita Cigarette Consumption In The United States, 20th Century

Carcinogens and Tobacco-Induced Cancers

Cancer Type Lung Likely Carcinogen Involvementa PAH, NNK (major) 1,3-butadiene, isoprene, ethylene oxide, ethyl carbamate, aldehydes, benzene, metals PAH NNK, NNN, other N-nitrosamines, aldehydes PAH, NNK, NNN NNN, other N-nitrosamines NNK, other N-nitrosamines, furan NNK, NNAL PAH, NNK 4-aminobiphenyl, other aromatic amines Benzene Heterocyclic aromatic amines

Larynx Nasal Oral cavity Esophagus Liver Pancreas Cervix Bladder Leukemia Colorectal

ETIOLOGY OF CANCER. Tobacco and ALCOHOL

MULTIPLICATIVE EFFECT OF ALCOHOL AND TOBACCO

RR of Oral and pharyngeal cancers relative to tobacco and alcohol intake

NICOTINIC PLAQUE

Conceptual Model For Understanding Mechanisms Of Tobacco Carcinogenesis

Cancer Susceptibility Syndromes

Familial Adenomatous Polyposis (FAP) Hereditary Non Polyposis Colon Cancer (HNPCC) Hereditary Breast and Ovarian Cancer (HBOC) Neurofibromatosis (NF type 1) Xerrodermal Pigmentosum (XP) MEN syndromes, Cowden syndromes, ect

(5-10% of Cancers)

VIRUSES
DNA VIRUSES RNA VIRUSES

Human Viruses with Oncogenic Properties

Virus Family Adenovirus Flaviviruses Hepadnavirus Herpesviruses Type Types 2, 5, 12 Hepatitis C (HCV) Hepatitis B (HBV) EBV Associated Human Tumors Cofactors Not associated with human cancer Hepatocellular carcinoma Hepatocellular carcinoma Aflatoxin, alcohol, smoking Burkitts lymphoma Immunoblastic lymphoma Nasopharyngeal carcinoma Hodgkins lymphoma Leiomyosarcomas Gastric cancers Kaposis sarcoma Pulmonary effusion lymphoma Castlemans disease Anogenital cancers and some upper airway cancers ? nonmelanoma skin cancer Merkel cell carcinomas ? Brain tumors ? Non-Hodgkins lymphomas ? Mesotheliomas ? Brain tumors ? Prostate cancer Adult T-cell leukemia/lymphoma Malaria Immunodeficiency Nitrosamines HIV infection HIV infection HIV infection Smoking, other factors EV, sunlight, immunesuppression Immunosuppression Uncertain

KSHV (HSV8)

Papillomaviruses

HPV-16, -18, -33, -39, others HPV-5, -8, -17, others

Polyomavirus

Merkel cell virus SV40 (monkey virus)

Retroviruses

JC virus BK virus HTLV-1

INFLAMMATION

The Contrasting Effects Of Inflammation And Immunity Associated Factors On Cancer

Chronic Inflammatory Conditions Associated with Tumor Formation

Pathologic Condition Sunburned skin, burn scar
Severe thermal injury Epidermolysis bullosa Gingivitis, lichen planus Lichen sclerosus Sialadenitis Sjgren syndrome, Hashimotos thyroiditis Asbestosis, silicosis Bronchitis (nitrosamines, peroxides) Reflux esophagitis, Barretts esophagus Hematochromatosis Liver cirrhosis Chronic pancreatitis

Associated Tumor(s) Basal cell carcinoma, squamous cell carcinoma (SCC), melanoma
Marjolins ulcer (SCC) SCC Oral SCC Vulvar SCC Salivary gland carcinoma Mucosa-associated lymphoid tissue lymphomas Mesothelioma, lung carcinoma Lung carcinoma Esophageal carcinoma Liver Hepatocellular carcinoma Pancreatic carcinoma

Etiologic Agent Ultraviolet light

Genetic, mechanical Asbestos fibers, silica particles Silica, asbestos, smoking Gastric acid, alcoholism, smoking Genetic Alcoholism Genetic (mutation in trypsinogen gene on chromosome 7), alcoholism, smoking

Inflammatory bowel disease, Crohns disease, chronic ulcerative colitis Cystitis, bladder

Colorectal carcinoma, small intestine carcinoma Bladder carcinoma

Chronic indwelling, urinary inflammation catheters

CANCER ASSOCIATED WITH INFLAMMATION CAUSED BY INFECTIOUS AGENTS

Pathologic Condition Hepatitis Mononucleosis AIDS Associated Tumor(s) Hepatocellular carcinoma B-cell non-Hodgkins and Burkitts lymphoma Non-Hodgkins lymphoma, squamous cell carcinoma, Kaposis sarcoma Nonmelanoma skin cancer Ovarian carcinoma, cervical/anal carcinoma Skin carcinoma in draining sinuses Prostate cancer Ocular adnexal lymphoma Gastric adenocarcinoma Gall bladder cancer Cholangiosarcoma, colon carcinoma Bladder, liver, rectal carcinoma, follicular lymphoma of the spleen Pathogen(s) Hepatitis B and C virus Epstein-Barr virus Human immunodeficiency virus, human erpes virus type 8 Papillomaviruses Neisseria gonorrhoeae, Chlamydia spp., human papillomaviruses Bacteria Gram() bacteria, others Chlamydia psittaci Helicobacter pylori Bacteria, gall bladder stones Opisthorchis viverrini, O. sinensis (liver flukes), bile acids Schistosoma hematobium, S. japonicum, irradiation, carcinogens

Warts Pelvic inflammatory disease, chronic cervicitis Osteomyelitis Chronic prostatitis Conjunctivitis Gastritis/ulcers Chronic cholecystitis Opisthorchiasis, Cholangitis Chronic cystitis

CHEMICAL FACTORS

Known or Suspected Chemical Carcinogens in Humans

Target Organ Lung Agents Tobacco smoke, arsenic, asbestos, crystalline silica, benzo(a)pyrene, beryllium, bis(chloro)methyl ether, 1,3-butadiene, chromium VI compounds, coal tar and pitch, nickel compounds, soots, mustard gas, cobalttungsten carbide powders Asbestos, erionite Tobacco smoke, alcoholic beverages, nickel compounds Tobacco smoke, alcoholic beverages Industries Aluminum production, coal gasification, coke production, hematite mining, painters, grinding in oil and gas Tumor Type Squamous, large cell, and small cell cancer and adenocarcinoma

Pleura Oral cavity

Esophagus

Insulation, mining Boot and shoe production, furniture manufacturer, isopropyl alcohol production

Mesothelioma Squamous cell cancer

Squamous cell cancer

Gastric
Colon Liver Kidney Bladder

Smoked, salted and pickled foods

Heterocyclic amines, asbestos Aflatoxin, vinyl chloride, tobacco smoke, alcoholic beverages, thorium dioxide

Rubber industry
Pattern makers

Adenocarcinoma
Adenocarcinoma Hepatocellular carcinoma, hemangiosarcoma

Tobacco smoke, phenacetin Renal cell cancer Tobacco smoke, 4-aminobiphenyl, benzidine, 2- Magenta manufacture, auramine Transitional cell cancer napthylamine, phenacetin manufacture

Prostate Skin
Bone marrow

Cadmium Arsenic, benzo(a)pyrene, coal tar and pitch, mineral oils, soots, cyclosporin A, PUVA
Benzene, tobacco smoke, ethylene oxide, antineoplastic agents, cyclosporin A

Coal gasification, coke production

Rubber workers

Adenocarcinoma Squamous cell cancer basal cell cancer

Leukemia, lymphoma

HEAD AND NECK CANCER

PHYSICAL FACTORS
Ionizing Radiation Ultraviolet light Radiofrequency and Microwave Radiation Electromagnetic Fields Asbestosis Nanoparticles

XP Skin cancer

DIETARY FACTORS
Energy Alcohol Dietary Fat Red Meat Fruits and Vagetable Fiber Folate Calsium Vitamin D Soy Products Carotinoids

Doll & Peto 35% of all cancer deaths may be preventable by alteration in diet

YOU ARE WHAT YOU EAT!

OBESITY AND PHYSICAL ACTIVITY

BMI > 30 Steroid Hormones Insulin/Insulinlike Growth Factors (IGF) Pathway

Summary of the Strength of the Observational Epidemiologic Evidence for Physical Activity as a Protective Factor and Obesity as a Risk Factor for Cancer, by Type of Cancer
Physical Activity Breast, postmenopausal Breast, premenopausal Colon Endometrium Esophagus, adenocarcinoma Kidney/renal cell Gallbladder Pancreas Non-Hodgkin lymphoma Prostate, aggressive Lung Ovary +++ ++ +++ + ? ? ? ? ? + + ? Overweight/Obesity +++ ++ (protection) +++ +++ +++ +++ ++ ++ + + ? ?

Thank you