Chapter 12
Cancer Epidemiology
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Gene-Environmental-Lifestyle
Interaction

Environmental-lifestyle factors


Cigarette smoking, excessive alcohol consumption,
poor diet, lack of exercise, excessive sunlight
exposure, sexual behavior (creates exposure to
viruses), radiation, hormones, drugs, viruses, bacteria,
pesticides, other environmental chemicals present in
air, water, food, soil, and the workplace
Epigenetic changes coupled with genetic
changes and environmental-lifestyle factors
cause the development of cancer

Changes are mitotically and meiotically heritable
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Epigenetics


Changes in the phenotype (appearance) or
gene expression caused by mechanisms
other than changes in the underlying DNA
sequence
Modifiable by lifestyle

Especially diet and pharmacological interventions
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Epigenetics

Methylation



Histone modifications


Addition of methyl group (CH3) to cytosine ring
Aberrant methylation can lead to silencing of
tumor-suppressor genes
Histone acetylation, alterations in chromatin
MicroRNAs (miRNAs)



Small RNA molecules
Target gene expression posttranscriptionally
Act as oncogenes or tumor-suppressor genes
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Genetics


Parental exposure prior to conception
In utero exposure



Nutrition, toxins, stressors, lifestyle
Exposure to toxins in breast milk after birth
Gene-environment interactions
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Environmental Risk Factors

Tobacco


Multipotent carcinogenic mixture
Linked to cancers of the lung, lower urinary tract,
aerodigestive tract, liver, kidney, pancreas, cervix
uteri, and myeloid leukemia
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Environmental Risk Factors

Diet

Xenobiotics
• Toxic, mutagenic, and carcinogenic chemicals in food
• Activated by phase I activation enzymes
• Defense mechanisms

Phase II detoxification enzymes
• Examples


Compounds produced in cooking fat, meat, or proteins
Alkaloids or mold byproducts
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Environmental Risk Factors

Obesity



Correlates with the body mass index (BMI)
Adipose tissue is active endocrine and metabolic
tissue
In response to endocrine and metabolic signaling,
adipose tissue releases free fatty acids
• Increased free fatty acids give rise to insulin resistance
and cause chronic hyperinsulinemia
• Correlates with colon, breast, pancreatic, and
endometrial cancers
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Environmental Risk Factors

Alcohol consumption


Risk factor for oral cavity, pharynx, hypopharynx,
larynx, esophagus, and liver cancers
Cigarette-alcohol combination increases a
person’s risk
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Environmental Risk Factors

Ionizing radiation

Emission from x-rays, radioisotopes, and other
radioactive sources
 Exposure causes cell death, gene mutations, and
chromosome aberrations
 Bystander effects
 Poor gene repair
 Changes in gap junction intercellular
communication
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Ionizing Radiation: Causes Cellular
Injury
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Environmental Risk Factors

Ultraviolet radiation




Causes basal cell carcinoma, squamous cell
carcinoma, and melanoma
Principal source is sunlight
Ultraviolet A (UVA) and ultraviolet B (UVB)
Promotes skin inflammation and release of free
radicals
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Environmental Risk Factors

Electromagnetic fields

Carcinogenic?
• Are they, or aren’t they?
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Environmental Risk Factors

Sexually reproductive behavior



Carcinogenic types of human papillomavirus
High-risk HPV
Physical activity

Reduces cancer risk
• Decreases insulin and insulin-like growth factors
• Decreases obesity
• Decreases inflammatory mediators and free radicals
• Increases gut motility
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Environmental Risk Factors

Occupational hazards

Substantial number of occupational carcinogenic
agents
• Asbestos
• Dyes, rubber, paint, explosives, rubber cement, heavy
metals, air pollution, etc.
• Radon
• Pesticides
• Toxic wastes
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Environmental Risk Factors

Air pollution

Outdoor
• Industrial emissions, arsenicals, benzene, chloroform,
formaldehyde, sulfuric acid, mustard gas, vinyl chloride,
and acrylonitrite

Indoor
• Cigarette smoke, radon
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