Cancer Prevention

• 1 in 5 Americans will have cancer if they survive to the 7th decade

• Cancer develops over many years, and is not deadly until very late in its course

• Precursor lesions can be identified in individuals at risk for cancer

• 39% of those who get cancer will die of it

• Cancer is prevented by eliminating precursor lesions

FACTS

Milestones in cancer prevention

• 1919 James Ewing identifies pre-malignant neoplasia

• 1761 John Hill: nasal carcinomas in snuff users (109)

• 1775 Percival Pott: scrotal cancer in chimney sweeps

• 1911 Peyton Rous: viral etiology of certain tumors

Cancer Prevention Research

Infectious

Disease

Nutritional

Science

Behavioral

Medicine

Pharmacology

Surgery

Cellular and

Molecular

Biology

Epidemiology

Imaging/

Screening

Public Health

Policy

Objectives

• Define cancer, the causes of cancer and how it develops.

• Describe the different types of cancer and the risks they pose to people at different ages and stages of life.

• Explain the importance of understanding and responding appropriately to self exams, medical exams, and symptoms related to different types of cancer.

• Discuss ways to prevent cancer and the implications of behavioral risks.

• Discuss cancer detection and treatment.

An Overview Of Cancer

• 2006, approximately 564,830 Americans died of cancer

• 1.4 million new cases diagnosed

• 1/3 of cancers are related to poor nutrition, physical inactivity, and obesity – preventable causes

What Is Cancer?

• Cancer – a large group of diseases characterized by the uncontrolled growth and spread of abnormal cells

• Neoplasm – new growth of tissue that serves no physiological function

• Tumor – clumping of neoplasmic cells

• Malignant - cancerous

• Benign - noncancerous

• Biopsy – microscopic examination of cell development

What Is Cancer? – cont.

• Metastasis – malignant tumors that are not enclosed in a protective capsule have the ability to spread to other organs

• Mutant cells – disruption of RNA and DNA within normal cells may produce cells that differ in form, quality and function from the normal cell

Disparities In Cancer Rates

• African Americans have the highest death rates from cancer

• The gap in cancer mortality rates is greater now than in 1975

• African Americans with certain cancers are more likely to go unstaged and less likely to receive treatment

• Men from poorer census counties have a 22% higher death rate from prostate cancer than their affluent county comparison groups

What Causes Cancer?

• External Factors – chemicals, radiation, viruses, and lifestyle

• Internal Factors – hormones, immune conditions, and inherited mutations

• Theories

– Cellular change/mutation theories

– Carcinogens

– Oncogenes/ protooncogenes

Factors Believed to Contribute to Global Causes of Cancer

Figure 16.2

Risks For Cancer

• Lifetime risk – the probability that an

individual, over the course of a lifetime, will develop cancer or die from it

• Relative risk – measure of the strength of the relationship between risk factors and a particular cancer

• Smoking – 30% of all cancer deaths, 87% of lung cancer deaths

• Obesity – 50% higher risk for breast cancer in postmenopausal women, 40% higher risk in colon cancer for men

Preventing Cancer through Diet and Lifestyle

Table 16.2

Reproductive And Hormonal Risks For Cancer

• Pregnancy and oral contraceptives increase a woman’s chances of breast cancer

• Late menarche, early menopause, early first childbirth, having many children have been shown to reduce risk of breast cancer

Occupational And Environmental Factors

Asbestos

Nickel

Chromate

Benzene

Arsenic

Radioactive substances

Cool tars

Herbicides/pesticides

Social And Psychological Factors

• Stress has been implicated in increased susceptibility to several types of cancers

• Sleep disturbances, diet, or a combination of factors may weaken the body’s immune system

Chemicals In Foods

• Sodium nitrate when ingested forms a potential carcinogen, nitrosamine

• Sodium nitrate is still used because it is effective in preventing botulism

• Pesticide and herbicide residues

Viral Factors

• Herpes-related viruses may be involved in the development of leukemia, Hodgkin’s disease, cervical cancer, and Burkitt’s lymphoma

• Epstein-Barr virus, associated with mononucleosis, may contribute to cancer

• Human papillomavirus (HPV), virus that causes genital warts, has been linked to cervical cancer

• Helicobacter pylori causes ulcers which are a major factor in the development of stomach cancer

Medical Factors

• Some medical treatments actually increase a person’s risk for cancer

• Diethylstilbestrol (DES) used 1940 to 1960 to control bleeding during pregnancy, the daughters of mothers that used DES were found to have an increased risk for cancers of the reproductive organs

• Estrogen supplementation

• Chemotherapy used to treat one form of cancer may increase risk for another type of cancer

Types Of Cancers

• Classification of cancers

– Carcinomas

– Sarcomas

– Lymphomas

– Leukemias

Breast Cancer

• 1 out of 8 women will develop breast cancer (lifetime risk)

• 1 in 227: birth to age 39 • 1 in 25: ages 40-59 • 1 in 15: ages 60-79 • Detection: mammograms, regular breast self-exams • Symptoms: lump in the breast, thickening, dimpling,

skin irritation, distortion or tenderness • Risk factors: family history, hyperplasia, long

menstrual history, obesity after menopause, oral contraceptives

• Treatment: lumpectomy, radical mastectomy, radiation, chemotherapy

• Prevention: exercise

Breast Self-Examination

Figure 16.5

Surgical Procedures for Diagnosed Breast Cancer

Figure 16.6

Colon And Rectal Cancers

• Third most common cancer in men and women with over 148,610 new cases diagnosed in 2006

• Risk factors: over 50 years old, obese, family history of colon or rectum cancer or polyps, diets high in fats, low in fiber, smoking, high alcohol consumption, lack of exercise

• 90% of colorectal cancers are preventable • Treatment: radiation, surgery, and

possible chemotherapy • Prevention: regular exercise, a diet heavy

in fruits and plant-origin foods, a health

Prostate Cancer

• Most common cancer in American men, excluding skin cancer

• In 2006, 234,460 new cases diagnosed

• 1 in 3 men will be diagnosed in their lifetime

• Prostate is a muscular, walnut-sized gland the surrounds part of the urethra. Its primary function is to produce seminal fluid.

• Symptoms: nonspecific, weak or interrupted urine flow, difficulty starting or stopping urination

• Risk factors: age, race, nationality, family history, diet, lifestyle, and vasectomy

• Prevention: diet high in lycopenes, vitamin E

Skin Cancer

• Long term effects of sun exposure can result in skin cancer

• Malignant melanoma, deadliest form of skin cancer

• Sun give off 3 types of harmful rays:

– UVA

– UVB

– UVC

• Prevention: limit exposure to harmful UV rays, drink more fluids than usual, apply cool compresses to skin, moisturize skin

Invasive cancer is the end stage of a long process of tumorigenesis

Colorectal Carcinogenesis

initiated adenomas invasive

10-20 years

•VIEW 1: Cancer is caused by

•Activation of oncogenes: K-ras, CTTNB1, c-myc

•Loss of tumor suppressor genes: APC, p53, TGFRII, MLH1

•VIEW 2: Cancer is caused by

•Abnormal stem cell activity

Colorectal Carcinogenesis

Understanding the biology of pre-malignant disease is the key to developing effective

prevention methods

• Which individuals are at risk and for what type of cancer?

• What are the best methods of identifying and monitoring pre-malignant disease?

• How can we safely and effectively arrest the progression of pre-malignant disease?

Understanding Risk

Cancer is a heterogeneous disease

• Who will get pre-malignant lesions?

• Which patients with pre-malignant lesions will

develop cancer?

• Is each lesion in a given patient the same type of lesion?

=

Understanding Risk for Cancer

• Environment:

– Toxic exposures

• Radiation

• Asbestos

• Genetics: • Family history

• Genetic testing

• Lifestyle: • tobacco

• diet

• exercise

• Personal history: • cancer

• pre-malignant disease

• chronic inflammatory diseases

Colorectal Cancer Risk

• Personal history

– Identification of adenomas

– Inflammatory bowel disease

– History of treated colorectal cancer

• Family history – Familial cancer predisposition syndromes

– Primary family member with colorectal cancer or adenomas

• Age

Identifying and monitoring pre-malignant disease

Survival following treatment for colorectal cancer

0

0.2

0.4

0.6

0.8

1

1.2

0 2 4 6 8 12

years following treatment

% s

urv

ivin

g

I

III

II

IV

SEER Data, 2005

Shifting the therapeutic target in breast cancer

1894: 100%

2004: 15% 1894: 0%

2004: 22%

Screening modalities

• PAP smear

• Mammography

• Colonoscopy/upper endoscopy

• CT scan, sputum cytologies

• PSA and digital exam

Effective screening

is lacking

Pancreatic cancer

Ovarian cancer

Risk Specific CRC Screening Recommendations

• Begin at age 50:

– Colonoscopy every 10 years

– Sigmoidoscopy every 5 years

– Annual FOBT (stool sample)

• Personal Hx, Family Hx:

– Earlier and more frequent colonoscopy

Prevention Modalities

• Eliminate or prevent pre-invasive disease before invasion develops

• Chemoprevention

• General health maintenance • Eat a healthy diet • Don’t smoke • Don’t drink too much • Exercise/ maintain optimal weight

• Surgery

Preventing cancer

General health maintenance • Healthy Diet • No smoking • ETOH in moderation • Exercise/optimal weight

Not good enough In high risk people

Social change is difficult and takes a long time

Surgery

Surgery for cancer prevention A success story…

Management of uncommon high risk conditions: Hereditary cancer syndromes Barretts Esophagus Pancreatic Intraepithelial Neoplasia

Breast cancer: treatment of ductal carcinoma in situ Colorectal cancer: removal of pre-malignant adenomas Cervical cancer: treatment of cervical intraepithelial neoplasia

Colonoscopy with polypectomy doesn’t work well enough

~30-40% of those at risk get a colonoscopy

Why is colorectal cancer still so common?

• Not fun: many people avoid it • Expensive

• Risk: perforation, bleeding ~3-5 per 1000 procedures

Prevention of breast cancer by

treatment of DCIS

• 30,000 US women per year diagnosed with DCIS in the US

• 60-80% of women with untreated DCIS will

develop invasive breast cancer

18-24,000 breast cancer cases prevented per

year with successful surgery and/or radiotherapy

for DCIS

Cancer Chemoprevention

• The use of pharmacological compounds to prevent the development of malignancy

• Development of successful chemoprevention requires an understanding of early colorectal tumorigenesis

Successes and Challenges

• Breast cancer: tamoxifen

• Prostate cancer: finasteride

• Colorectal cancer: celecoxib

• Women’s Health Initiative

• Cervical cancer vaccine

Breast Cancer Prevention Trial

-age 60

-35-59 years

of age with

5-yr cancer

risk 1.66

-H/O LCIS

Tamoxifen

20 mg/d

Placebo

Endpoints: Invasive and

non-invasive

breast cancer

ER status

5 years

18,882 women

Prostate Cancer Prevention Trial

18,882 men

age 55

PSA < 3.0

Finasteride

5 mg/d

Placebo

Endpoints: End of study

biopsy for all

participants

PSA

7 years

Colorectal Cancer Chemoprevention: Results from Prospective Randomized Trials

• Dietary

modification

• Calcium

supplements

• Aspirin

unsuccessful

20-30% fewer advanced lesions

~30% fewer advanced lesions

• Selective

Cox-2 inhibitors

57-74% fewer advanced lesions

Objectives

• Define cancer, the causes of cancer and how it develops.

• Describe the different types of cancer and the risks they pose to people at different ages and stages of life.

• Explain the importance of understanding and responding appropriately to self exams, medical exams, and symptoms related to different types of cancer.

• Discuss ways to prevent cancer and the implications of behavioral risks.

Vaccination against human papilloma virus

• HPV infection is associated with development of cervical cancer and other anogenital tumors

• HPV infection rates are estimated as between 2-26%, depending upon the country

• Vaccination against HPV prevents cervical intraepithelial neoplasia in women at risk for cervical cancer

What can we do to prevent cancer?

Be good healthy diet exercise regularly maintain healthy weight don’t smoke alcohol in moderation

Know your risk and seek appropriate

evaluation or therapy for your risk level

Support prevention research

Ongoing Work

• Understand the mechanisms of cancer development to develop new treatments

• Individualize treatment, balancing risks and benefits of intervention

• Continue to promote social change necessary to achieve healthy lifestyles and access to preventive health care