Mednotes

L10 Cancer Causes and primary prevention of Cancer

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tagscancer, lecture
aliasesL10 Cancer Causes and primary prevention of Cancer

16 min read

Overview

This lecture covers how epidemiologists assess evidence for causation, then works through the major environmental and behavioural causes of cancer (tobacco, diet, infectious agents, HPV vaccination, radiation), a run-through of risk and protective factors by cancer site, and finishes with the scale of preventable cancer burden and NZ prevention policy.

Burden of cancer and global risk factors

  • Cancer is the 2nd leading cause of death globally: an estimated 10 million deaths in 2022, about 1 in 5 deaths worldwide (WHO). In 2022, 70% of cancer deaths occurred in low- and middle-income countries, worsened by relatively poor early detection and treatment access.
  • IARC (2014): the total annual economic cost of cancer was estimated at US1.71 trillion in 2025 terms). About half of all cancers could be avoided with current knowledge, but health promotion alone is insufficient; adequate legislation is important.
  • Leading global risk factors for cancer DALYs, 2010 vs 2019 (age-standardised rate, with % change): smoking led both years (774.1 to 677.3, -12.5%), followed by alcohol use, high BMI, unsafe sex, high fasting plasma glucose, ambient particulate matter pollution, and occupational asbestos exposure. Diet low in fruits fell from rank 10 (2010) to rank 12 (2019); second-hand smoke rose from rank 11 to rank 10 over the same period.

Assessing evidence for causation

  • Disease causation is analysed via three groups of factors (adapted from Bhopal):
    • Host factors: genetics, age, gender, behaviours (e.g. smoking), height and weight.
    • Agent factors: e.g. virulence of an organism, serotype, antibiotic resistance, cigarette tar content, type of glass in a car windscreen.
    • Environmental factors: home overcrowding, air composition, food, radiation, workplace hygiene, weather, food contamination, animal/human contact, asbestos, cooling towers.
  • Whether a disease is mainly genetic or environmental: genetic disease is stable in incidence and clusters in families; environmental disease shows incidence varying rapidly over time or between genetically similar populations. Example spectrum from most genetic to most environmental: Down syndrome, diabetes, asthma, heart attacks, stroke, lung cancer, car crashes.
  • To assess evidence for causation: gather all available evidence, judge study type/design and its place in the hierarchy of evidence, then critically appraise each individual study.
  • Critical appraisal of a study checks: internal validity (chance, bias, confounding), causal criteria, and external validity (generalisability).
  • A risk or protective factor for cancer meets many causal criteria (timing, size of effect, dose-response, plausibility, etc). Example relative risks (RR) and attributable risks: RR = 20 for 30+ cigarettes/day, causing 90% of lung cancer; RR = 25 for HPV causing 98% of cervical cancer; RR = 10 for alcohol causing 50% of oral cancer; RR = 6 for Helicobacter pylori causing 60% of stomach cancer.

Carcinogens and their classification

  • Carcinogens are all about us, within us, and essentially inescapable; many naturally occurring substances are carcinogenic. Whether an agent poses a real human cancer risk depends on where it is, what we do with it, how long we are exposed, and our natural susceptibility (e.g. genetic predisposition).
  • IARC (International Agency for Research on Cancer) classifies agents by carcinogenicity to humans: Group 1 carcinogenic, Group 2A probably carcinogenic, Group 2B possibly carcinogenic, Group 3 not classifiable, Group 4 probably not carcinogenic.
  • Historical estimate (Adami et al 2001) of cancer mortality attributable to factors in developed countries: tobacco 30%, diet in adult life including obesity 30%, alcohol 3%, perinatal effects and excessive growth 5%, food additives including salt 1%, sedentary life >3% (excludes its contribution via obesity), biological agents including viruses 5%, reproductive factors 3%, ionising and UV radiation 2%, occupational factors <5%, environmental pollution 2%, medical products and procedures 1%, high penetrance genes 2%.
  • Current estimate (WHO 2020): about 1/3 of cancer deaths are due to 5 leading behavioural and dietary risks - tobacco use, high BMI, low fruit and vegetable intake, lack of physical activity, and alcohol. Tobacco is the single most important modifiable risk factor for cancer. Infections (e.g. hepatitis, HPV) cause up to 25% of cancers in low- and middle-income countries.

Tobacco

  • Chronic tobacco smoke exposure drives a stepwise progression in airway epithelium: normal basal ciliated columnar epithelium -> squamous/flattened cells (metaplasia) -> cells with atypical nuclei (dysplasia) -> atypical cells with basement membrane breach and early invasive cancer.
  • Tobacco alone causes cancers of the lung, larynx, pancreas, kidney, and bladder. Combined with alcohol, it also causes cancers of the oral cavity and oesophagus.
  • Lung cancer risk from smoking is determined by: amount smoked daily, duration of smoking, and depth of inhalation.
    • Smokers have RR of 20 compared with non-smokers.
    • Passive smoke exposure carries RR of 1.2 compared with non-exposed people.
    • Risk decreases soon after stopping smoking.

Diet and dietary contaminants

  • Foods to limit or avoid: processed and red meats (linked to increased bowel cancer risk); sugar-sweetened drinks and refined carbohydrates (promote weight gain, raising cancer risk); high-calorie foods high in fat, sugar and salt (promote weight gain); fried foods (deep frying produces acrylamide, associated with increased cancer risk).
  • Foods that can reduce cancer risk: fruit and vegetables (fibre, antioxidants, other beneficial compounds); whole grains and legumes (high fibre, can lower bowel cancer risk); plant-based diets (may be associated with lower cancer rates).
  • Food contaminants: aflatoxins are produced by fungi and found especially in stored maize and groundnuts in hot, humid parts of the world.
    • In a Shanghai population, hepatitis B surface antigen (HBsAg) status and dietary aflatoxin B1 (AFB1) exposure interact synergistically (multiplicatively, not additively) on the relative risk of hepatocellular carcinoma: approximate RR ~1 with neither factor, ~7 with either AFB1 or HBsAg alone, and ~60 with both together.

Infectious agents

  • Key infectious agents and the cancers they cause, ranked by relative importance (adapted from Montesano & Hall 2001, 1 = highest): Helicobacter pylori - stomach (1); Human papillomavirus (HPV) - cervix, ano-genital (2); Hepatitis B virus - liver (3); Hepatitis C - liver (4); HIV associated with human herpesvirus-8 - Kaposi sarcoma (5).

HPV vaccination

  • In NZ, HPV vaccination began in 2008. From 2008-2016 it targeted girls and women. Since 2017, it has been free for everyone (males and females) aged 9-26. Children in year 7 or 8 are offered it at school or via their GP; it is also available via GPs and other primary care groups.
  • The vaccine is Gardasil 9, covering HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58.
  • HPV vaccination protects against cervical cancer and other HPV-related diseases later in life. It targets the HPV types responsible for about 90% of cervical and other HPV-related cancers, and 90% of genital warts. Since 2008, genital wart incidence has decreased by about 80%. Protection appears long-lasting.

Radiation

  • Two broad types are covered: UV (e.g. sunlight) and ionizing radiation (e.g. X-rays).
  • Radiation types and the cancers they cause: X-rays and gamma radiation - all sites; solar radiation, sun beds, UV - skin; radon-222 - lung; radium - bone; radioiodines (including iodine-131) - thyroid; plutonium-239 - lung, liver, bone; phosphorus-32 - leukaemia; thorium-232 - liver, leukaemia; neutrons and sources of alpha/beta particles - various sites.
  • Approximate single-exposure medical X-ray doses (millirem): pelvis 70, abdomen 60, chest 10, dental 1.5, hand/foot 0.5, mammogram (2 views) 72, nuclear medicine 400. CT doses: full body 1,000, chest 700, head 200. Medical procedures account for 96% of human exposure to human-made radiation.
  • Ionizing radiation (X-rays, gamma rays) sits at the highest-energy, highest-frequency end of the electromagnetic spectrum, distinct from and far higher energy than everyday non-ionizing EMF sources such as mobile phones/microwaves and mains power (ELF fields).
  • Global mobile phone subscriptions grew rapidly between 2000 and 2009, from about 750 million to about 4,700 million (and from about 12 to about 68 per 100 inhabitants), illustrating the scale of RF/microwave exposure growth relevant to this discussion. [slide does not elaborate on a health effect from this exposure]

Risk and protective factors by cancer site

  • Lung: smoking; asbestos; talc containing asbestos fibres; coal tars; soots; arsenic; hexavalent chromium; nickel compounds; mustard gas; bischloromethyl ether; chloromethylmethyl ether; radon; occupational exposure in aluminium manufacture, coal and gas production, iron and steel founding, isopropyl alcohol production, boot and shoe production, some underground mining, and furniture/cabinet making; possible link with cannabis use.
  • Melanoma: fair skin, blue eyes, red hair; familial or genetic syndromes; UV exposure; some sun blocks (via behavioural effects); sunbed use.
  • Other skin cancers: UV exposure; soot; various compounds; arsenic.
  • Breast: older age at first birth (17% attributable); obesity; HRT; oral contraceptive pill; alcohol; lack of exercise. Protective: parity, breastfeeding, plant-based diet (EPIC study 2025).
  • Cervix: sexual behaviour of men and women; HPV infection (types 16, 18, 31, 33 and 13 other types); smoking. Barrier contraception is somewhat protective.
  • Ovary: risk falls with increasing parity - relative risk 2.12 with 0 children vs 1 (reference) with 3+ children - and with longer oral contraceptive use, falling from RR 1.0 in never-users to RR 0.42 after 15+ years of use. The protective effect of OC use attenuates with time since stopping: risk reduction per 5 years of use is 29% if less than 10 years have elapsed since ceasing, 19% at 10-19 years, and 15% at 20-29 years.
  • Bladder: smoking; aromatic amines; occupational exposure (dyes, particularly aniline dyes; tanning); Schistosoma haematobium infection.
  • Kidney: smoking; phenacetin-containing analgesics.
  • Leukaemia: ionising radiation; therapeutic radiation; chemotherapeutic agents; benzene; HTLV-1 retrovirus; service in the Vietnam war (specifically linked to CLL).
  • Lymphoma: HIV/immune suppression; Burkitt’s lymphoma (linked to Epstein-Barr virus); H. pylori (stomach lymphoma); possible link with some pesticides.
  • Lip: pipe smoking; UV exposure; cigarette smoking.
  • Oral cancer: smoking; alcohol; betel nut quid chewing; oral snuff; HPV; cannabis.
  • Larynx: smoking; alcohol; possible link with HPV 16 & 18.
  • Colorectal: increased risk from diet low in fruit/vegetables/fibre, diet high in red and processed meat, obesity, animal fats, alcohol, low physical activity, and smoking. Protective: low-dose aspirin, calcium supplementation, and screening by flexible sigmoidoscopy or colonoscopy (removal of adenomas).
  • Anal cancer: HPV 16 & 18.
  • Liver: hepatitis B; hepatitis C; chronic cirrhosis (alcohol or other cause); excess iron consumption or absorption; Aflatoxin; vinyl chloride (specifically causes angiosarcoma).
  • Gallbladder: chronic inflammation; chronic typhoid or paratyphoid carriage; obesity.
  • Stomach: increased risk from H. pylori infection, nitrites and nitrosamines, smoking, obesity, and alcohol. Protective: fresh fruit and vegetable intake, citrus fruit intake, antioxidant intake, Mediterranean diet, regular aspirin use.
  • Brain tumours: some genetic conditions (e.g. neurofibromatosis, tuberous sclerosis); HIV/AIDS; medical radiation; cellphone use is flagged as “probably not” a cause.

Additional IARC statements

  • Iodine deficiency and supplementation affect thyroid cancer risk in children exposed to radioactive iodine.
  • Oral cancer screening saves lives.
  • Combined estrogen-progestogen oral contraceptives and combined estrogen-progestogen menopausal therapy are carcinogenic to humans.
  • OC use increases risk of breast, cervix, and liver cancer, but decreases risk of endometrial and ovarian cancer.
  • Combined menopausal therapy increases risk of breast cancer and endometrial cancer.
  • Emissions from household combustion of solid fuel cause cancer.
  • There is a clear dose-response relationship between exposure to co-workers’ smoke and lung cancer risk.
  • Breast and colorectal cancers are associated with alcohol consumption; even modest alcohol drinking has a clear association with increased breast cancer risk, described as a major concern.

Prevention and policy

  • What can be done: individuals can significantly lower their cancer risk through healthy lifestyles and by participating in recommended screening and vaccination programmes. Governments and organisations can implement policies and create environments that support healthy choices and reduce exposure to risk factors. More research is needed, including on gene-environment interaction.
  • NZ context: the Cancer Control Agency (within the Ministry of Health) published the “Cancer Prevention Report” (Pūrongo Ārai Mate Pukupuku) in 2022, focusing on six areas: tobacco, alcohol, poor nutrition and excess body weight, insufficient physical activity, excessive UV exposure, and chronic infections.
  • Key points from the 2022 report: about 30-50% of all cancers worldwide can be prevented; the cancer burden is not the same for everyone, since environments strongly influence a person’s risk and create inequities; Te Tiriti o Waitangi responsibilities include preventing cancer; there are good opportunities for prevention.
  • Modelled opportunities for prevention by addressing modifiable risk factors: about 75% of health loss from lung cancer could be prevented, mainly by reducing smoking; 50% of health loss from uterine cancer by reducing high BMI; 65% of health loss from bowel cancer by reducing dietary risks, alcohol use, high BMI, smoking, and physical inactivity.

Summary

  • Understanding aetiology is crucial to decreasing the worldwide cancer burden.
  • Genetics and environmental factors interact to determine cancer risk.
  • Specific cancers have specific risk and protective factors.
  • Important modifiable factors include alcohol, tobacco, dietary factors, infectious agents, physical activity, and ionizing radiation.
  • A large portion of the cancer disease burden is preventable.

Self-test

  1. Describe the three groups of factors used to analyse disease causation, with an example of each.
  2. Distinguish the clues that suggest a disease is mainly genetic from those suggesting it is mainly environmental.
  3. Describe the steps taken to assess evidence for a causal relationship, from gathering evidence to appraising an individual study.
  4. List the three components checked when critically appraising a study for causation.
  5. What relative risk links smoking (30+ cigarettes/day) to lung cancer, and what proportion of lung cancer does it cause?
  6. List the five IARC groups for classifying carcinogenicity to humans, from most to least certain.
  7. List the cancers caused by tobacco alone, and the additional cancers caused by tobacco combined with alcohol.
  8. What three factors determine an individual’s risk of lung cancer from smoking, and what is the relative risk for passive smoke exposure?
  9. List two dietary factors that increase cancer risk and two that reduce it, from the lecture’s food lists.
  10. Describe the interaction between hepatitis B infection and dietary aflatoxin B1 exposure on liver cancer risk, including whether it is additive or synergistic.
  11. Which infectious agent is ranked as most important for causing cancer in the lecture’s table, and which cancer does it cause?
  12. Describe how HPV vaccination policy in NZ has changed since 2008, and name the vaccine and the HPV types it covers.
  13. List the cancers linked to specific ionizing radiation sources: radon-222, radium, radioiodines, and phosphorus-32.
  14. Where does ionizing radiation sit on the electromagnetic spectrum relative to mobile phone and mains power exposure?
  15. Describe how ovarian cancer risk changes with parity and with duration of oral contraceptive use.
  16. List the risk factors and the protective factors for colorectal cancer described in the lecture.
  17. Distinguish the risk factors for stomach cancer from its protective factors.
  18. A patient with chronic hepatitis B infection who also has high dietary aflatoxin exposure asks about their liver cancer risk. Using the figures given, explain why their risk is much higher than either factor alone would suggest.
  19. According to the 2022 NZ “Cancer Prevention Report”, what proportion of health loss from lung cancer, uterine cancer, and bowel cancer could be prevented by addressing modifiable risk factors, and what is the main driver in each case?
  20. Explain how genetic and environmental factors together determine overall cancer risk, drawing on both the causation framework and the site-specific risk factors covered in this lecture.

Answers

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