Cancer Screening and Development Concepts

• All cancers stem from mutations in cellular DNA.

Carcinogens and Mutagens

• Carcinogens are agents that either cause or promote cancer.
• Mutagens are carcinogens, that directly mutate DNA.
• Some carcinogens promote cancer growth by stimulating cell division rather than directly altering DNA.
• All mutagens are carcinogens, but not all carcinogens are mutagens.

Cancer Susceptibility and Causation

• Genetic susceptibility includes inherited factors affecting the body's response to cancer threats.

Cancer Causation

• Includes environmental and genetic factors that cause mutations.
• Initiating mutations can be either inherited or non-inherited.
• Progressional mutations are environmental, originating inside or outside the body.

Cancer Initiation

• Most initial mutations are acquired, not inherited.
• Mutations in somatic stem cells result from external factors like environmental carcinogens, and biological processes like inflammation or DNA replication errors
• Inherited mutations are less common, affect every cell (germline mutations), and while initiation cannot be prevented, progression can be.

Somatic vs. Germline Mutations

• Somatic mutations occur in non-germline tissues and are not inherited, only found in tumors affecting individuals.
• Germline mutations are present in egg or sperm cells, can be inherited, and cause family cancer syndromes, impacting inherited cancer risk.
• Mutations occurring in both somatic and germline mutations during progression may be preventable.
• Genetic counselling is recommended for inherited cancer risk concerns.

Carcinogenesis in Context

• Cancer is primarily an environmental disease.
• 90-95% result from environmental factors, with only 5-10% being genetics.
• Environmental factors include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), and radiation (up to 10%), and pollutants.

Understanding Relative Risk

• Relative risk assesses cancer development risk due to specific factors.
• A relative risk of 1.0 is average.
• A relative risk of 0.5 means 50% lower than average.
• A relative risk of 1.5 means 50% higher than average.
• A relative risk of 10 means 10 times higher than average.

Identifying Carcinogens

• This requires both laboratory and epidemiological studies.
• Agencies such as IARC, NIH, CDC, and EPA, part of the Carcinogen Patrol, evaluate substances for their carcinogenic potential.

IARC Groups

• Agents categorized into Group 1 (carcinogenic to humans).
• Group 2A (probably carcinogenic).
• Group 2B (possibly carcinogenic).
• Group 3 (unclassifiable).
• Group 4 (probably not carcinogenic).

Human Carcinogens

• The NTP Report on Carcinogens (RoC) classifies substances as known or reasonably anticipated to be human carcinogens.
• The current RoC lists around 240 substances.

Carcinogenesis Factors

• Carcinogens typically cause specific cancers, not all.
• Individual susceptibility, genetic background increasing mutation risk, exposure mode, how one encounters carcinogens like ingestion or inhalation, and exposure duration/degree influence cancer development.
• No carcinogen predictably causes cancer in everyone, all the time, under any circumstances.

Cigarette Smoke Carcinogens

• Cigarette smoke contains 250 harmful chemicals, with 69 known carcinogens including benzene, formaldehyde, polonium-210, and tobacco-specific nitrosamines.

Risk Factors for Cancer

• A risk factor is a characteristic, condition, or behavior that increases the probability of developing cancer.
• Risk Factor may or may not be a causal factor.
• Causal (mutation causing) risk factors directly cause mutations. Ex: asbestos.
• Non-causal risk factors increase risk without direct mutations Ex: age.
• Risk factors significantly impact cancer screening recommendations.

Risk Factors That Cannot Be Altered

• Age, genetics, gender, ethnicity, inherited mutations, inherited immunodeficiency increases the risk of cancer.
• Defects in detecting/destroying abnormal, mutated cells, impaired ability to eliminate infections, family history, or personal history.
• World region influences cancer risk based on geographical factors.
• Genetic Cancer Syndromes: Certain inherited mutations in tumor suppressor genes lead to hereditary cancers, such as BRCA1/2 (breast and ovarian cancer) and APC (familial adenomatous polyposis, FAP).
• Syndromes display high penetrance, affecting the likelihood of those affected.
• Top genetic cancers caused by inherited genes: Testicular, thyroid, and laryngeal.

Environmental Risk Factors

• Smoking, viral infections, obesity can be altered for cancer prevention.
• Treatable factors= chronic inflammation, dietary deficiencies, and hormonal status.
• Where one lives=endemic exposures and lifestyle. Moving can alter risk.

Smoking & Obesity

• Correlation between smoking and lung cancer in the US (1900-2002).

Cancers Caused by Cigarettes

• Lung, trachea, bronchus, esophagus, larynx, mouth/throat, kidney, pancreas, ureter, nasal cavity/sinuses, bladder, liver, stomach, cervix, uterus, colon, rectum, ovary, and acute myelogenous leukemia

Prevalence & Demographics

• 2021 Statistics: 11.5% of U.S. adults (28.3 million) smoke cigarettes.
• Higher smoking rates include women vs men, individuals aged 25–65 & non-hispanic adults.
• Gen Z has 29% currently smoking.
• Lower-income households and less-educated individuals.

Lung Cancer in Never-Smokers

• 84% of women and 90% of men with a lung cancer diagnosis have smoked
• 12% of Lung Cancer patients in the U.S are never-smokers.
• Lung cancer genomic alterations differ in smokers vs never-smokers.
• Causes in never-smokers include radon gas, asbestos, secondhand smoke, air pollution, or a familial (genetic) predisposition.
• Trends In the UK, never-smoker lung cancer patients rose to 28% (2008-2014) .
• Worldwide, 15-20% of men and over 50% of women with lung cancer are never-smokers.
• In Asia, 60-80% of women with lung cancer are never-smokers.

Vaping

• Over multiple races, education, and ethnicity, most e-cigarette users are current or former smokers.
• E-Cigarettes:70% of smokers use e-cigarettes to quit, but there's no FDA authorization for this use.
• Vaping among former smokers is linked to relapse.
• FDA/CDC Advice:Avoid and be aware of nicotine addiction and toxicity concerns. Banned fruit-flavored vape products in 2020 (not menthol).

Vaping Generation Z

• 63% of e-cigarette users are aged 18-24.
• Banned fruit-flavored vape products in 2020 (not menthol).
• Nicotine affects brain development in young e-cigarette users.
• Severe lung disease arising suddenly in otherwise healthy individuals and additive vitamin E acetate strongly linked to EVALI outbreaks

Obesity and Cancer Risk

• Types of Cancer: Breast (post-menopausal women), colon, rectum, endometrial, esophagus, gallbladder, kidney, liver, ovarian, pancreas, stomach, thyroid, multiple myeloma, Non-Hodgkin lymphoma, male breast, mouth/throat, larynx, aggressive prostate, meningioma.
• Obesity Mechanisms: Metabolic and Endocrine Abnormalities:
• Alterations: Fat cells make estrogen & cytokines. Excess estrogen production stimulates cell growth, decreases cell death, & increases ROS leading to DNA mutations.
• High Insulin/Insulin-like Growth Factor Levels: Adipokines (cytokines) stimulate cell growth and inflammation.
• Chronic inflammation& oxidative stress, excess ROS damages DNA.
• Causes of Imbalance: Hyperglycemia & Elevated Lipids are causes of imbalance.
• Factors include: Nutrient Deficiencies, Increased Muscle Activity, and Impaired Mitochondrial Function which cause Lack of antioxidants, more ROS, and damaged production.
• Weight loss can reduces cancer risk.
• 150 billion/year are direct/indirect medical costs and potential factors gut microbiome, genetics, patterns and sleep routines

Obesity Epidemic

• Since 1975. obesity increased, 1.9 billion are overweight, 65k are obese.
• Treatable: Obesity
• More of the world population live in countries or underweight.
• Most in the U.S. are 37.9% of an obese epidemic.
• Studies show bariatric surgery increases 3 years of life and can reduce cardiovascular deaths
• GLP-1 is a hormone released by the intestines during digestion.
• The hormone also enhances insulin secretion,delays the digestion process & suppresses appetite.

Alcohol and Cancer

• Increased Risk: Heavy intake can raise the risk of oral, laryngeal,or liver cancer.
• Moderate to high drinking can produce EtOH conversion, DNA damage, increased cell division, increased estrogen,cirrhosis,folate depletion and ROS damage.
• Moderate- Drinking can be less than 1 drink a day. Heavy is >4 glasses.

Diet & Cancer Risk

• High fat (especially with high heat), processed meats, concentrated sugar, high omega-6, low fiber, and red meats increase cancer risk.
• Lower risk with fruits+ vegetables, bok choy, sprouts, cabbage, kale, and Broccoli.
• Modulates gene expression and decreases inflammation for the body.
• Vitanin E, B carotene and folate can all increase cancer risk for men.

Physical Activity & Cancer

• Reduces, or has not found preventative steps towards any type of cancer or leukimia.

Infection & Cancer

• Hepatitis and HPV increase the risk of cancerous viral infections in the liver and cervix.
• Vaccines exist to combat these viruses and prevent cancer from spreading.
• Parasitic causes of Bladder/Colon cancer: Schistosomes.

Radiation Exposure

• Types of Radiation: Ionizing, which create free radicals like alpha and UV-A.
• All radiation increases cellular breakdown. Can penetrate even the deepest layers of skin.
• Sun exposure can be harmful.
• Industrial exposures can decrease health due to dust and gases.

Cancer Takeaways

• Most is through behavior change.
• Lung cancer could be linked to smoking
• There are many factors, not always a cause
• Prevention is superior and behavior chance
• Diet
• Age
• Screening is essential when benefits outweigh the cost

Childhood Cancer Key Facts in the USA (2020)

• American has shown that most young americans don’t die from cancer.
• But top causes of death include accidents, suicides, and violence from firearms.
• Childhood includes similar causes that go undetected and untreated.
• This is a reason why cancer is still the leading cause of death among American children.
• Funding only includes 4%, as opposed to other types.
• Top cancers are acute leukemia and brain spinal cord tumors

Acute Leukemias: Key Details

• Comes from mutation or abnormalities
• Can be myeloid, or lymphoid
• Relation comes from a normal rate turning cancerous
• Results : Symptoms can vary depending on the rate of infection

Screening For Key Indicators

• Goal- detect the chance of early treatment and prevention.
• Test results that are false or negative do not allow for prevention. Overwhelm a healthy state for the patient.

HPV

• Does not have a negative relationship with tests today.
• HPV vaccination is important.

Biases with Screening

• Not all cancers are aggressive, and doctors can miss the chance to treat them.
• Physical and patient education is key.

Key Takeaways

• The goal of detection is early prevention of the disease
• Use different methods and consider the risk of false diagnosis

Assess your knowledge of cancer screening effectiveness, lead time, and characteristics of cancers in children. Questions cover minimal residual disease, cancer susceptibility factors, and the initiation stage of cancer development, along with the differentiation of initiators versus promoters.