Wirsma Arif Harahap Surgical Oncologist Surgery Department - Andalas University

 According to GLOBOCAN, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occurred in  56% of new cancer cases in 2008 occur within developing regions) and cancer mortality (63% of cancer deaths).

 Cancer is neither rare anywhere in the world, nor confined to high-resource countries. "Striking differences in the patterns of cancer from region to region are observed,"  Cervix and liver cancers are much more common in developing regions of the world, whereas prostate and colorectal cancers are more common in developed regions.

The most commonly diagnosed cancers worldwide are : lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung (1.38 million, 18.2% of the total), stomach (0.74 million, 9.7%) and liver cancers (0.69 million, 9.2%).

 Cancer prevalence : 4.3 / 1000 people SIRS 2007 : Breast cancer cases (16.85%). Breast cancer incidence : 26 per women.  Cervical cancer : 16 per women

“ Distribution and determinants of disease frequency in human populations”

1775 British surgeon, Percival Pott reported probably the first description of occupational carcinogenesis in the form of scrotum cancer among chimney sweeps.

Tight corsets and cancer 1842 Rigoni-Stern, Italian physician, observed that married women in the city were getting cervical cancer, but nuns in nearby convents weren’t. He also observed that nuns had higher rates of breast cancer, and suggested that the nuns’ corsets were too tight.

CriteriaRisk Factor for Disease 1) Timing  Exposure occurs before development of disease or during its progression 2) Strength  Is dose-dependent  Cessation of exposure can modify disease 3) Prevalence  Occurs in multiple populations 4) Relationship to other risk factors  Is independent  Can also act synergistically 5) Plausibility  Produces structural ‡ or functional changes which are events in mechanism of disease ‡ anatomic or molecular

1700s: tobacco and cancer Reports of cancer risks associated with tobacco in the 18th century included snuff taking and nasal cancer, reported by Hill in 1761, and pipe smoking and lip cancer by von Soemmering in 1795.

 Tobacco and Lung Cancer  Asbestos and Lung Cancer  Leather Industry and Nasal Cancer  Dyes and Bladder Cancer  Ionizing Radiation and Many Cancers  DES and Vaginal Adenocarcinoma  EBV and Burkitt’s Lymphoma  HPV and Cervical Cancer

 Uncover new etiologic leads ◦ study of the distribution of cancer ◦ quantify the risk associated with different exposures and host factors  Promote insights into the mechanisms of carcinogenesis  Assess efficacy of preventive measures  Investigate predictors of survival

 Cohort  Case-Control  Cross-Sectional (Prevalence)  Other

 Descriptive Studies ◦ Incidence, mortality, survival ◦ Time Trends ◦ Geographic Patterns ◦ Patterns by Age, Gender, SES, Ethnicity  Analytic Studies ◦ Case-control ◦ Cohort

What are the goals of epidemiology ? 1. Identify the causes of cancer 2. Quantify risks 3. Identify risk groups 4. Understand mechanisms 5. Identify syndromes

New Terminology

Prevention Primary = directed to susceptibility stage Example: Needle exchange to prevent AIDS, HPV vaccine Secondary = directed to subclinical stage Example: Screen for cervical cancer with Pap Smear Tertiary = directed to clinical stage Example: Treat diabetic retinopathy to prevent blindness

Incidence is a measure of the risk of developing some new condition / new disease within a specified period of time. Prevalence is the ratio of the total number ofratio cases / disease in the total population in a period of time. Incidence Vs Prevalence

Age (years/female)

Incidence is usually more useful than prevalence in understanding the disease etiology: for example, if incidence rate of population of a disease increases, then there is a risk factor that promotes the incidence.

The five-year survival rate is a termsurvival rate for estimating the prognosis of a particular disease.prognosis What is a cancer survival rate? Cancer survival rates or survival statistics tell you the percentage of people who survive a certain type of cancer for a specific amount of time. Understanding Cancer Survival : Mayo Cliniic

Cancer statistics often use an overall five- year survival rate. For instance, the overall five-year survival rate for bladder cancer is 80 percent. That means that of all people diagnosed with bladder cancer, 80 of every 100 were living five years after diagnosis.

5 years survival rate of breast cancer

WORLD CANCER STATISTIC  WHO

INDONESIA

Cancer risk factor

What are some dietary risk factors? High fatColon, breast High caloriesUterine Low fiberColon MicronutrientsLung (?) Diet contaminentsLiver

What are alcohol-associated cancers? Oral Pharynx Esophagus Larynx Liver

 Ionizing  Non Ionizing ◦ Ultraviolet ◦ Electromagnetic

Ionizing Radiation : Leukemia (AML, but not CLL) Breast Lung Thyroid Head and neck cancer

Excessive sun tanning

Non-Ionizing Radiation (UV/sun) Basal cell Squamous cell Melanoma

4-Aminobiphenyl Bladder Arsenic Lung, skin Asbestos Lung, pleura, peritoneum Benzene Leukemia Benzidine Bladder beta-Naphthylamine Bladder Coal tars and pitches Lung, skin Mineral oils Skin Mustard gas Pharynx, lung Radon Lung Soot, tars, and oils (polycyclic hydrocarbons) Lung, skin Vinyl chloride Liver Wood dusts (furniture) Nasal sinuses

Viruses and cancer

 Helicobacter pylori increases risk of stomach cancer

HP-associated Disease

 Etiology, distribution, and control of disease in families and with inherited causes of disease in populations  Includes ◦ family studies ◦ molecular epi studies w/ genetic components ◦ traditional cohort + case-control studies w/ family history components

 CDKN2A -- major melanoma susceptibility gene  Frequency of mutations varies in families ◦ 2 cases<5% ◦ 3 – 5 cases20 – 24% ◦ >6 cases50%

Cloned Familial Tumor Suppressor Genes RetinoblastomaRB113q Wilms’ tumorWT111p Li-Fraumeni syndromep5317p Neurofibromatosis 1NF117q Neurofibromatosis 2NF222q von Hippel-Lindau VHL3p Familial melanoma 1p169p Familial breast 1 BRCA1 17q Familial breast 2BRCA213q Basal cell nevus PTC9q221996

causal relations …..tobacco and lung cancer High relative risk (odds ratio) Consistency Dose-response Temporal relationship Plausible mechanism

Lung cancer deaths occur 2 decades after smoking incidence

Progress Report on Cancer Control in Canada, Health Canada

Increasing riskReducing risk ProbableExcess weight/BMIPhysical activity AlcoholAspirin Family history * Hormone replacement therapy Vegetables PossibleTobacco smokingOral contraceptives Insulin/hyperinsulinaemia/ related factors Other NSAIDs Calcium Folate/folic acid * Approximately 2-fold increase in risk to 1 st -degree relatives Little and Sharp, accepted.

 Hormonal Factors ◦ Early age at menarche ◦ Late age at menopause ◦ Multiparity ◦ Late age at first full- term pregnancy ◦ OCs ◦ HRT  Family history ◦ BRCA1/BRCA2 – 5% ◦ Other - ?  Post-menopausal obesity  Physical Activity (inverse association)  Alcohol use

 Meat consumption  Selenium (inverse association)  Family history  Androgens

 HPV Electron micrograph showing HPV particles (red and green) Smoking Smoking – OR

 Tobacco control the priority  Dietary modification - plant foods  Avoid known carcinogens in occupations and general environment  Hepatitis B Vaccination  Sex education for HIV, cervix cancer  Promote physical exercise and weight reduction  Sun avoidance

Use only effective strategies Educate professionals and public Base on Natural History of cancer Screen at right ages and frequency Maintain high quality Ensure adequate facilities available Organization

Prevention: Tobacco control30 years Dietary modification years Infection control40 years Screening10 years Treatment 5 years