- 2nd only to heart disease (23% of deaths)

- smoking most dramatic risk factor (lung)

- overall incidence increasing, actual incidence decreasing in females, same in males (excluding lung)

Cancer

- Heart Dx, Cancer, Stroke, Lower Respiratory Dx, Accidents

(25.4, 23.2, 5.6, 5.3, 5.1%)

5 most common causes of death

- Lung Bronchus, Prostate, Colorectum

Top 3 Male (All Ages) Cancer deaths

- Leukemia, Brain & Nervous system, Bones & Joints

Top 3 Male <20 Cancer deaths

- Leukemia, Brain & Nervous system, Endocrine Systems

Top 3 Female <20 Cancer deaths

- Breast, Uterine/Cervix, Leukemia

Top 3 Female 20-39 Cancer Deaths

- Prostate (28%), Lung/Bronchus (15%), Colorectum (9%)

Top 3 Male New Cases of Cancer

- Breast (28%), Lung/Bronchus (14%), Colorectum (10%)

Top 3 Female New Cases of Cancer

- most tumors in organs present in both sexes affect males more than females

- exceptions to this are

Thyroid, Salivary Glands, Gallbladder

- this causes an increased risk of death from cancer (52/62% male/female)

- account for 14/20% of cancer deaths in male/female

Obesity

- lymphomas

Increasing Incidence of Cancer

- stomach, uterus, liver, colorectum, breast, lung, prostate

Decreasing Incidence of Cancer

- common cancer among US women

- risk increases with immigration to US

Breast, endometrium & ovarian

- rare among women who marry circumcised men

Cervical Cancer

- Rare among blacks

Skin Cancer

- Risk increases with immigration to high risk areas (Africa)

- risk associated with Esptein-Barr greater than with local population

Burkitt's Lymphoma

- highest in blacks, then American whites, then japanese

Prostate Cancer

- risk highest in mainland China

Nasopharyngeal Cancer

- risk highest in Japan and Chile

Gastric Cancer

- risk highest in Orient and Africa

Liver Cancer

- development of tumors requires these two steps in order and with significant frequency

1. Initiation --> 2. Promotion

- exposure of cells to an appropriate agent

- binding of highly electrophilic intermediates to DNA

- non-enzymatic, rapid formation of covalent adducts

- covalent adducts (irreversible) become basis of memory for future replication

- can be direct or indirect

Initiation

- do not require metabolic activation

- uncommon

- Ex: divalent metals (Nickel), chemotherapy drugs, alkalators, benzyl chloride

Direct initiators

- require metabolic activation before becoming carcinogenic

- more common than direct type

- Ex: aromatic amines, amides, azo dyes, benzidine, beta-naphthylamine, aflotoxin, nitrosamine, amides, vinyl chloride, polychlorinated biphenyls, aromatic hydrocarbons (smokers)

Indirect initiators

- metabolically activated by the hepatocytes and greatly increases the risk of liver cancer

- fungal metabolite contaminating beans and grain

Aflatoxin

- P-450 variant causes much greater ability to activate these things in tobacco smoke and increase risk of lung cancer

Aromatic hydrocarbons

- activated by liver, detoxified, then unconjugated by the bladder's glucuronidase causing increased risk for bladder cancer

Beta-naphthylamine

- effects are reversible

- phenolic compounds and hormones are common

- chronic inflammation or antigen stimulation

Promotion of Carcinogens

- direct-acting alkylating agents are linked to this cancer

Lymphomas/Leukemias

- aniline dyes are linked to this type of cancer

Urinary bladder

- Nitrosamines/Amides are linked to these cancers

Esophageal/gastric and GI tumors

- vinyl chloride is linked to this type of cancer

Angiosarcoma of liver

- increased risk of skin cancer is linked to this elemental molecule

Arsenic

- type of UV associated with causing skin tumors

- caused formation of pyrimidine dimers in DNA, melanomas and skin cancers

UVB (280-320 nm)

- may be particulate (worse) or electromagnetic

- induce mutation directly or by formation of free radicals

- leukemia in adults, papillary thyroid cancer in children

- skin, bone, gut resistant

Ionizing radiation

- H. Pylori infection is linked to increased risk of these two cancers

Lymphoma & adenocarcinoma of stomach

- causes genital and skin warts and laryngeal papillomas

- can lead to in situ and invasive squamous cell cancer of vulva and cervix

Human Papilloma Virus (HPV)

- linked to increased risk for Burkitt's lymphoma and nasopharyngeal carcinoma

- common with AIDS patients

Epstein-Barr virus (EBV)

- can cause hepatocellular carcinoma following infection

Hepatitis-B or C virus

- only RNA oncogenic virus that has been found that is linked T-cell leukemia/lymphoma risk

- endemic to Japan and parts of the caribbean

HTLV-1