Cancer: Causes and Risk Factors – Comprehensive Study Notes

Cancer: Causes and Risk Factors – Study Notes

Overview

• Cancer risk increases with age due to longer exposure to carcinogens and more time to accumulate multiple mutations.

• Cancer results from a combination of genetic factors and environmental factors; the balance shifts with age and exposure.

• A variety of agents can contribute to cancer development, including viruses, bacteria, radiation, chemicals, and lifestyle factors.

Genetics vs Environment

• Inheritance: Only about 5-10% (approximately 5–10%) of cancers are caused by inherited genetic mutations.

• Environment: The majority, about 90-95%, are attributed to environmental factors.

• Diet, tobacco use, infections, obesity, alcohol, and other lifestyle factors contribute substantially to cancer risk.

• Specific cancers show different contribution patterns (examples listed below as approximate values):

  • Diet: 30-35%

  • Tobacco: 25-30%

  • Infections: 15-20%

  • Obesity: 10-20%

  • Alcohol: 4-6%

  • Other/environmental factors (including exposure to carcinogens): 10-15%

• Some cancers have higher familial risk due to inherited variations, but most risk is environmental.

• Emerging field: genetic variations and individual susceptibility to carcinogens are being studied to understand inter-individual differences in risk.

SNPs, Genome, and Personalized Medicine

• Human genome basics:

  • The Human Genome has been sequenced with about 3 billion base pairs

  • Humans are about 99% identical, leaving roughly 3 million differences between individuals.

• SNPs (Single Nucleotide Polymorphisms):

  • The differences among individuals at a single nucleotide position.

  • These variations can be recorded across all SNP locations on all chromosomes.

  • SNPs can be used to determine individual susceptibility to carcinogens and to tailor therapies.

• SNP profiles and cancer risk:

  • SNP profiles (A–F) illustrate individual genetic signatures.

  • Normal population vs. cancer patient comparisons show certain SNP patterns associated with higher cancer risk for specific organs (e.g., kidney cancer).

  • Example schematic: A patient with a particular SNP (e.g., SNP B) may have higher than normal risk for a given cancer type.

• Drug response and SNPs:

  • Individual SNP profiles can predict response to standard drug therapy (some profiles respond, others do not).

  • Sorting of SNP profiles helps personalize treatment decisions (e.g., which patients are likely to respond to a given regimen).

Known and Suspected Carcinogens

• A satirical slide lists: “Everything You Eat” and “Everything You Breathe” as carcinogens, with a joke about broccoli reducing risk.

• Real-world message: many everyday exposures contribute to cancer risk; focus on evidence-based factors like tobacco, alcohol, diet, infections, and environmental exposures.

• Tobacco and tobacco smoke:

  • Tobacco smoke contains dozens of known carcinogens.

  • Tobacco use accounts for a large portion of cancer deaths, particularly lung cancer.

  • Strong dose–response relationship between number of cigarettes smoked, age of smoking onset, depth of inhalation, and lung cancer deaths.

  • Carcinogens in tobacco include: aminostilbene, arsenic, benz[a]anthracene, benz[a]pyrene, benzene, chrysene, cadmium, nickel compounds, polycyclic aromatic hydrocarbons (PAHs), N-nitrosamines, polonium-210, and more.

  • Lung cancer risk increases with cigarette consumption (e.g., 5x, 10x, 15x corresponding to exposure levels in some data).

• Other chemical carcinogens and promoters:

  • 2 types of carcinogens: mutagenic and promoters

    • mutagenic

      • directly cause DNA mutations; they change the actual sequence of the DNA

      • tobacco can mutate the DNA

        • combined exposure amplifies cancer risk, increasing chances of cancers in the mouth and throat among others.

    • Promoters

      • do not mutate DNA directly but increase the likelihood of acquiring mutations by promoting cell proliferation or causing tissue damage/inflammation

      • Promoters are agents or processes that increase proliferation, induce chronic inflammation, or cause tissue damage; they can include infectious agents, hormones, drugs, chemicals, and physical factors.carcinogens: substances known to promote cancer developments

      • alcohol does not mutate DNA, but it does kill cells and stimulates cell proliferation

      • promoter examples:

        • Hormones: Estrogen; Estrogen plus progesterone; Ovulation; Testosterone

        • Drugs: Oral contraceptives; Anabolic steroids; Analgesics; Diuretics

        • Infectious agents: Hepatitis B and C viruses; Schistosoma species; Helicobacter pylori; Malaria parasites; Tuberculosis bacillus

        • Chemical agents: Betel nut/lime; Chewing tobacco; Bile; Salt; Acid reflux

        • Physical/mechanical trauma: Asbestos; Gallstones; Coarsely ground corn; Head injury; Chronic irritation/inflammation (e.g., tropical ulcers, chronic ulcerative colitis, chronic cystitis, chronic pancreatitis)

    • alcohol + smoking >> increased chances of developing mount and throat cancer

      • they work synergistically to product greater effect than action singley

  Infectious Agents and Cancer

  • Main infectious contributors to cancer deaths are largely preventable through sanitation, general preventative health care, vaccines, and public health measures.

  • Epstein–Barr virus (EBV): Associated with Burkitt’s lymphoma.

  • Hepatitis B virus (HBV) and Hepatitis C virus (HCV): Associated with liver cancer.

  • Human Immunodeficiency Virus (HIV) infection leads to depressed immune surveillance and increased susceptibility to viral infections; Kaposi’s sarcoma–associated herpesvirus (KSHV) is a notable cancer-associated virus in this context.

  • Human papillomavirus (HPV): A major cause of cervical cancer and other anogenital cancers; links to other cancers of the oropharynx, etc.

• HPV Vaccines and Cervical Cancer Prevention

• HPV vaccine landscape:

  • Gardasil (quadrivalent): Covers HPV types 6, 11, 16, 18.

  • Cervarix (bivalent): Covers HPV types 16 and 18.

  • Gardasil-9 (9-valent): Covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

  • propalactic vaccine: preventative

• Expression system and adjuvant:

  • Gardasil and Gardasil-9: recombinant vaccine expressed in yeast Saccharomyces cerevisiae; aluminum-hydroxyphosphate sulfate adjuvant.

  • Cervarix: recombinant vaccine produced with a baculovirus system; A504 adjuvant.

• Cervical cancer impact:

  • HPV strains 16 and 18 are responsible for about 70% of cervical cancers.

  • Gardasil 9 expands coverage to additional oncogenic HPV strains to protect against more cervical and anogenital cancers.

• Practical notes on vaccines:

  • HPV infections are highly prevalent; vaccination aims to prevent the most high-risk infections before exposure.

  • Vaccines have been shown to prevent most cervical cancers when administered prior to sexual activity onset in population-level programs.

Diet, Obesity, and Energy Balance

• Main cancer death contributors include diet and obesity-related factors:

  • Diet: around 30-35% of cancer risk (environmental contribution).

  • Obesity and sedentary lifestyle: around 15-20%.

  • Obesity is linked to multiple cancer sites (e.g., breast, colon, esophagus, pancreas, kidney, endometrium, liver, etc.).

• Obesity and cancer risk mechanisms:

  • Obesity increases circulating inflammatory molecules and sex hormones, as well as insulin levels.

  • These changes create a pro-carcinogenic environment via inflammatory signaling, hormonal regulation, and metabolic stress.

  • obesity

    • increase in growth factors (ex: insulin)

    • increase in circulating sex hormones

    • increase in circulating “bad” inflammatory factors

  • exercise

    • decrease in growth factors (ex: insulin)

    • decrease in circulating sex hormones

    • decrease in circulating “bad” inflammatory factors

• Energy balance concept:

  • Neutral balance: Calories consumed = Calories used; weight remains constant.

  • Positive balance: Calories consumed > Calories used; weight increases.

  • Negative balance: Calories consumed < Calories used; weight decreases.

  • A simple representation: let Cin = calories consumed, Cout = calories used. Then:
    $C<em>{in} = C</em>{out} <br>ightarrow ext{weight stable}$
    C{in} > C{out}
    ightarrow ext{weight gain}
    C{in} < C{out}
    ightarrow ext{weight loss}

• Link between nutrition and cancer progression:

  • Food, nutrition, obesity, physical activity, and cellular processes (DNA repair, cell cycle, apoptosis, inflammation, immunity, proliferation, differentiation, hormonal regulation) are interconnected in cancer risk and progression.

  • Carcinogen metabolism and nutrient signals can influence DNA repair capacity and cell fate decisions, thereby affecting cancer development.

• Physical activity, obesity, and diabetes connection:

  • Exercise and physical activity can modify circulating hormones, growth factors, inflammatory signals, and insulin sensitivity.

  • High obesity and sedentary behavior are associated with higher cancer risk; increasing physical activity and reducing adiposity can lower cancer risk.

  • Type II diabetes links to cancer risk via insulin resistance, hyperinsulinemia, and inflammation; physical activity helps mitigate these pathways.

• Practical implications:

  • Weight management, physical activity, and a balanced diet are practical strategies to reduce cancer risk.

  • Public health efforts targeting obesity reduction can have significant cancer prevention impact.

Key Takeaways on Cancer Causes and Prevention

• Genetic predisposition plays a role but most cancers arise from environmental and lifestyle factors.

• Tobacco use remains a major, largely preventable cause of cancer, with a strong dose–response relationship for lung cancer.

• Alcohol and tobacco can act synergistically to increase certain cancer risks (e.g., mouth and throat cancers).

• Infectious agents (EBV, HBV, HCV, HPV, HIV-related infections) contribute to cancer risk; vaccines and infection control can reduce these risks.

• HPV vaccination (Gardasil, Cervarix, Gardasil-9) significantly reduces cervical cancer risk by targeting high-risk HPV types, with vaccines now covering additional strains for broader protection.

• Obesity and poor energy balance contribute to cancer risk via hormonal, inflammatory, and metabolic pathways; improving diet and increasing physical activity are key preventive strategies.

• Understanding SNPs and genomics opens avenues for personalized risk assessment and targeted therapies, though many cancers still arise from modifiable factors.

• The table of known or suspected tumor promoters highlights the broad range of influences—including hormones, drugs, infections, chemicals, and physical factors—and their cancer-site specific effects.

• Overall, prevention strategies emphasize reducing known carcinogen exposures, maintaining a healthy weight, staying physically active, vaccination against oncogenic infections, and leveraging genomics for personalized risk and therapy where applicable.

Important References and Concepts (for quick recall)

• Carcinogens vs promoters: direct DNA mutagens vs factors that increase mutation likelihood via proliferation/inflammation.

• Key HPV vaccines and strains:

  • Gardasil: HPV types 6, 11, 16, 18; 0-2-6 month schedule; protects against genital warts and cervical cancers linked to these types.

  • Cervarix: HPV types 16, 18; 0-1-6 month schedule; protects against the most oncogenic HPV strains.

  • Gardasil-9: 9-valent vaccine covering types 6, 11, 16, 18, 31, 33, 45, 52, 58; aims for broader protection against cervical and other HPV-related cancers.

• Major cancer risk contributions by category:

  • Diet: ~30-35%

  • Obesity: ~15-20%

  • Infections: ~15-20%

  • Tobacco: ~25-30%

  • Alcohol: ~4-6%

• Energy balance and cancer: balance between calories consumed and calories used governs weight and metabolic state, which in turn influences cancer risk through hormonal and inflammatory pathways.

• Public health implication: sanitation, vaccines, lifestyle modification, and obesity prevention can reduce a large fraction of cancer deaths.