11.2 Recorded Lecture - Etiology and Prevention of Cancer

• Cancer arises from a complex interplay of multiple etiologies, including genetics, epigenetics, and tissue interactions.
• Avoiding high-risk behaviors and minimizing exposure to carcinogens can prevent many cancers.
• Environmental, lifestyle, and genetic factors are key contributors to cancer development.
• Genetic alterations and epigenetic changes drive cancer.
• Risk of certain cancers can be significantly influenced by exposures during in utero and early life.

Developmental Plasticity

• Developmental plasticity refers to the extent to which an organism's development depends on its environment.
• Nutrition and other environmental factors impact cellular pathways during gestation.
• A single genotype can produce a diverse range of adult phenotypes due to developmental plasticity.
• Persistent epigenetic adaptations in early development, influenced by maternal and paternal factors, can increase susceptibility to cancer and other chronic diseases.
• Early undernutrition during the first trimester of pregnancy is particularly critical for disease outcomes in adulthood.
• Small changes in the developmental environment can lead to altered phenotypes and adult responses.

Tobacco Use

• Cigarette smoking is a major carcinogen and the leading cause of cancer and cancer-related deaths.
• All forms of smoking, including cigars, hookahs, pipes, and e-cigarettes, contain nicotine and are not safe alternatives.
• Smoking elevates the mutation burden and is linked to lung adenocarcinoma, larynx, liver, and kidney cancer.
• Cigarette smoke triggers an inflammatory response and increases reactive oxygen species, causing oxidative stress.
• Oxidative stress is a risk factor for numerous diseases as it can modify cellular proteins.

Nutrition

• Diet, weight, and physical activity levels impact the risk of developing cancer.
• Epigenetic processes interact with genetic changes during carcinogenesis and tumor progression.
• The Mediterranean diet has been shown to reduce mortality rates from chronic illnesses, including cardiovascular disease, degenerative diseases, and cancer.
• Blue zones, areas with high longevity, often feature diets similar to the Mediterranean diet, low in meat and high in fruits, vegetables, and pasta.
• Daily coffee consumption is a common practice in blue zones.
• Diet has a significant influence on cancer development and its rate of progression.
• Obesity, including childhood obesity, has increased in developed countries over the past 20 years.
• Insulin/IGF axis, sex hormones, and adipocyte-derived cytokines are three main factors linking obesity to cancer.
• Obesity-related alterations in adipose tissue lead to insulin resistance, hyperglycemia, dyslipidemia, hypoxia, and chronic inflammation.
• Obesity increases estradiol levels, potentially promoting the growth of estrogen-dependent cancers.
• Obesity leads to adipocyte dysfunction and immune cell recruitment, resulting in cytokine production, inflammation, and fibrosis.
• Chronic inflammation is a risk factor for cancer.

Alcohol and Physical Activity

• Alcohol consumption increases the risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum.
• Contributing factors include oxidative stress and nutritional deficiencies, particularly folate and vitamin B.
• The World Health Organization recommends 600 metabolic equivalent minutes of activity per week, equivalent to 150 minutes of brisk walking or 75 minutes of running.
• Increased leisure time physical activity is associated with a reduced risk of developing 13 different types of cancer.
• Physical activity lowers insulin and IGF levels, reduces obesity, modulates inflammatory mediators, decreases oncogenes, lowers metabolic and sex hormone levels, improves immune function, and enhances cytochrome P450 activity.

Air Pollution

• Long-term exposure to ambient air pollution increases mortality and morbidity while shortening life expectancy, primarily due to cardiovascular and respiratory diseases and lung cancer.
• Particulate matter in the air elevates oxidative stress, generates reactive oxygen species, causes DNA oxidative damage and mutagenesis, stimulates pro-inflammatory factors, and induces senescence.
• Indoor pollution is generally worse than outdoor pollution, partly due to indoor cigarette smoke.

Ionizing & UV Radiation

• Ionizing radiation triggers apoptosis and senescence, potentially leading to endothelial dysfunction by altering vasodilation and hemostasis, inducing oxidative stress and inflammation, and inhibiting angiogenesis.
• Exposure to ionizing radiation is linked with increases in multiple cancers.
• Radiation can activate oncogenes, deactivate tumor suppressor genes, and cause chromosomal changes, impacting gene expression, mitochondrial function, and cell death.
• Radiation is a potent DNA-damaging agent, disrupting cellular regulation.
• Cell transformation, involving loss of homeostatic control, is more common with high radiation exposure.
• Progeny of irradiated cells are affected through the long-term effects of DNA damage.
• While UV radiation is essential for vitamin D production, it is the most preventable cause of skin cancer.
• Individuals with fair skin, freckles, or those who burn easily are at a higher risk.
• UV radiation leads to basal cell carcinoma, squamous cell carcinoma, and melanoma.
• Melanomas are cancers that form in melanocytes or pigment cells.
• Basal cell carcinoma is cancer in the lower part of the epidermis.
• Squamous cell carcinoma is cancer in the flat cells on the skin surface.

EMR

• Most exposure to EMR (electromagnetic radiation) comes from wireless communication devices and equipment, including radio and television signals, radar, satellite stations, microwave ovens, WiFi, and computer screens.
• Most exposure arises from near-field sources, such as mobile telephones.
• There is a lack of a clear dose-response relationship and difficulty in reproducing the effects of EMR.
• Concerns exist regarding the long-term effects on children who start using mobile devices at a young age.

Infection

• Viral infections can directly cause cancer.
• HPV (human papillomavirus) is the most common sexually transmitted virus in the U.S. and is the cause of almost half of all vaginal, vulvar, and penile cancers.
• Vaccines have been developed for the most significant HPV types.