Bahan Ajar Dr. H. Wirsma Arif Harahap, SpB(K)Onk.

CANCER EPIDEMIOLOGY

&

CANCER RISK FACTOR

Wirsma Arif Harahap Surgical Oncologist

What this lecture about ?

•

Learning more about cancer epidemiology

•

Investigating risk factors implicated cancer

development

•

Learning about prevention and early detection

of cancer

Disease Free Survival / Interval

•

The time that a person with a disease lives

without known recurrence; DFS is major

clinical parameter used to evaluate the

efficacy of a particular therapy, which is

usually measured in 'units' of 1 or 5 yrs

Survival Analysis

•

To describe the survival times of members of a

group

- Survival function

- Hazard function

- Kaplan-Meier curves

•

To compare the survival times of two or more

groups

Etiology

&

RISK FACTORS

•

HEREDITARY

HEREDITARY

•

MUTATION

– BRCA 1 : breast cancer

– BRCA 2 : ovarial cancer

– HNPCC : colon cancer

Environmental Risk Factors

•

Tobacco

– Most important cause of cancer

– Leading preventable cause of death

– Linked to cancer of the lung, lower urinary tract, upper aerodigestive tract, liver, kidney, pancreas, and cervix uteri

Environmental Risk Factors

•

Ionizing radiation

– Emission from x-rays, radioisotopes, and other radioactive sources

– Exposure causes cell death, gene mutation, and chromosome aberrations

– A u ulatio of utatio s → a er – Bystander effects - not directly radiated

Environmental Risk Factors

•

Ultraviolet radiation

– Causes basal cell carcinomas, squamous cell carcinomas, melanomas

– Principle source is sunlight (UVA, UVB)

– “pe ifi ge e utatio s → i fla atio

(TNF alpha, free radicals) reduce immune surveillance

Environmental Risk Factors

•

Electromagnetic fields

–

Carcinogenic ?

•

Are they, or are ’t they?

•

Living arround high voltage wire.

Environmental Risk Factors

• Diet

–

Xenobiotics

•

Toxic, mutagenic, and carcinogenic

chemicals in food

•

Examples

–Compounds produced in the cooking of fat meat or protein – polycyclic aromatic

hydrocarbons

–Industrial contaminants (diesel exhaust, pesticides in food & water)

Environmental Risk Factors

• Obesity*

– Body mass index = Weight kg Height (cm) 2

Underweight < 18.5

Normal 18.5 – 24.9 Overweight 25 – 29.9

Obese 30 – 34.9 I 35 – 39.9 II Extreme Obesity > 40 III also waist circumference

men 40 inches women 35 inches * colon,breast,pancreas,uterine

Environmental Risk Factors

•

Obesity

–

Adipose tissue is active endocrine and

metabolic tissue

–

In response to endocrine and metabolic

signaling, adipose tissue releases free fatty

acids

•

Leads to i suli resista e → hro i

hyperinsulinemia

•

Correlates with

colon, breast, pancreatic

Environmental Risk Factors

•

Exogenous hormones

– Hormone replacement therapy

•

Endogenous hormones

– Adipose tissue metabolizes androgen precursors to estrogens (breast, uterine cancer)

– Adipose ells ↑ ir ulati g i suli levels a d IGF-1 →

↓ liver sy thesis “HBG leadi g to ↑ estradiol

– High i suli levels → ↑ ovaria , possi ly adre al

synthesis of androgens.

Environmental Risk Factors

•

Alcohol

– Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus and liver cancer (breast –

maybe 2007)

Environmental Risk Factors

•

Hepatitis B/C



hepatocellular cancer

•

Sexual reproductive behavior

–

Carcinogenic

human papilloma virus

•

HPV-16 (60%), HPV-18 (10%), HPV-31/35

(5% each)

–

cervical cancer

–

Persistence

–

prerequisite for cancer

Environmental Risk Factors

•

Physical activity

–

Reduces cancer risk

• ↓ i suli a d IGF-1

• ↓ o esity

• ↓ i fla atory ediators a d free radi als • ↑ gut otility

Environmental Risk Factors

•

Occupational hazards

–

Substantial number of occupational

carcinogenic agents

•

Asbestos

•

Dyes, rubber, paint, explosives, rubber

Environmental Risk Factors

•

Air pollution

– Inhales 20,000 L/day – potential for appreciable doses of pollutants

– Industrial – arsenicals, benzene, chloroform, formaldehyde, sulfuric acid, mustard gas, vinyl chloride and acrylonitrites

– Radon – radioactive gas, uranium decay – rocks

Risk factors associated with the development

of breast cancer

family history and genetic factors

previous history of breast cancer in one breast fibrocystic disease (atypical hyperplasia)

ionizing radiation

age at menarche and menopause

age at first delivery, number of children nulliparity

oral contraceptives and hormone replacement therapy

Risk factors associated with the development

of breast cancer

diet

alcohol

physical activity

ORAL CANCER

Wirsma Arif Harahap

Konsultan Bedah Tumor

What is oral cancer?

•

Usually squamous cell (epithethial)

•

Abnormal neoplasm of the mouth

•

Found in most cases by a dentist or the

person themselves.

Statistics

•

30,000 people a year diagnosed

•

8,000 deaths

•

Higher then:

• Cervical cancer

• Hodgkin’s disease

• Brain cancer

• Liver cancer

• Testicular cancer

• Kidney cancer

Statistics on Oral Cancer

•

Accounts for 2% of all cancers

•

40 years of age and older are at a higher risk

•

Over 35,000 people will be diagnosed

•

Over 7,600 will die from the disease

Who is at risk?

•

People over the age of 40

• Men vs. Women

• Ethnicity

• Socioeconomic Status (SES)

•

Being a heavy smoker and drinker

•

Chronic irritation

•

People with HPV-16 and HPV-18 are at

slightly higher risk

HPV and oral cancer

•

1% of oral cancer is linked to HPV

•

HPV infects epithelial cells

•

On a cellular level the mouth is similar

to the vagina and cervix

•

Smoking and drinking alcohol can

promote HPV invasion

Signs and symptoms

• Sores or lesions that won’t heal

• Lump or thickening in the cheek

• White or red patches on the gums, tonsils, or mouth

• Chronic sore throat

• Difficulty swallowing

• Difficulty moving mouth or tongue

• Numbness in any area of the mouth

Staging

Side Effects of Treatment

• Swelling

• Sore mouth

• Difficulty chewing, swallowing, or talking

• Changes to appearance

• Weight loss

• Inability to wear

dentures for a period of time

• Fatigue

• Lowered immune system

• Nausea

• Vomiting

• Mouth sores

Linkage to Oral Cancer

•

Persistent gum disease can lead to oral cancer

and other potential life threatening conditions

like:

– Heart Disease

– Stroke

– Diabetes

– Chronic Kidney Disease (CDK)

– Preterm Birth

Health Disparities

•

Health Disparities are differences in health

conditions or outcomes among specific

population groups in the United States.

– Some include:

• Environmental factors – rural and urban poor

• Economical factors – working poor

• Cultural factor – language barrier

• Accessibility to care

• Quality of care

Prevention

•

Ways To Educate People

– Advertising & Visuals

– Developing Culturally Appropriate Messages

– Educate in local schools, colleges, health clinics, churches, and community centers

•

Why It Is Important

– Early Detection

Tumor Immunology

Wirsma Arif Harahap

The scope of lecture

1) Immune responses that develop to cancer cells 2) Escape of cancer cells

3) Therapies: clinical and experimental

Immunologic perspective

Cancer cells can be viewed as

altered self cells

that have escaped

n o r m a l g r o w t h - r e g u l a t i n g

mechanisms.

Evidence for Tumor Immunity

 

Spontaneous regression:

melanoma, lymphoma

 

Regression of metastases after removal of

primary tumor:

pulmonary metastases from renal carcinoma

 

Infiltration of tumors by lymphocytes and

macrophages:

melanoma and breast cancer

 

Lymphocyte proliferation in draining lymph

nodes

 

Higher incidence of cancer after

immunosuppression, immunodeficiency (AIDS,

neonates), aging, etc.

Tumor Immunity

 

General Principles

 

Tumors not entirely self

  Express non-self proteins

 

Immune-mediated recognition of

tumor cells may be positive

mechanism of eliminating

transformed cells

Tumor Antigens

 

Tumor Specific Antigens

  Present only on Tumor cells

  Recognized by cytotoxic T cells

  Bound by class I MHC

  Several antigens in humans found that are

not unique for tumor, however are

generally not expressed by normal tissue

  Melanoma-associated antigen-1 (MAGE-1):   Embryonal protein normally expressed in testis

Tumor Antigens

 

Tumor Associated Antigens

 

Not unique to tumors, shared by

normal cells

 

Differentiation- specific antigens

  CALLA (CD10) in early B cells   Prostate specific antigen PSA

Antitumor Effector

Mechanisms

  Cytotoxic T-cells

  MHC restricted CD-8 cells (viruses)

  NK cells

  Destroying tumor cells without prior sensitization

  Macrophages   Ifn-gamma

  Humoral Mechanisms

Antitumor Effector

Mechanisms

Cytotoxic T-cell NK cell

Macrophage Humoral

Mechanisms

Tumor-specific Immune

Response

Tumor Immunology

 

Cancer immunosurveilance:

immune system can recognize and

destroy nascent transformed cells

 

Cancer immunoediting:

immune system kill and also induce

changes in the tumor resulting in tumor

escape and recurrence (epigenetic

IMMUNOSURVAILLANCE

  Argument for:

  Increased cancer in immunodeficient hosts

  200x increase in immunodeficiencies (lymphoma)   X-linked lymphoproliferative disorder (XLP

  EBV related

  Escape Mechanism Theories

  Selective outgrowth of antigen-negative variants   Loss or reduction of HLA (escape T-cells)

  Immunosuppression (Tumors secrete factors

Tumor killing

Non-specific: NK cells,

γδ

T cells

(NKG2D), macrophages, NK T cells

Antigen-specific: Antibody (ADCC,

opsinization); T cells (cytokines,

Fas-L, perforin/granzyme)

How to think of error?



An individual failing



Only the minority of cases amount from

negligence or misconduct; so it

’

s the

wrong diagnosis



Doctors will hide errors



May destroy many doctors inadvertently

(the second victim)



A systems failure



This is the starting point for redesigning

the system and reducing error

How to respond? Tactics

 Reduce complexity

 Optimise information processing

 checklists, reminders, protocols

 Automate wisely

 Use constraints

 for instance, with needle connections

 Mitigate the unwanted side effects of change

The Pathway to Increased Patient

Safety

Performance Improvement Projects Cultural & Process Change Data Analysis Healthcare Incident Investigation Team Event Reporting Tool