Environmental Exposure and Disease

In 2020 the International Agency for Research on Cancer confirmed that tobacco smoke alone causes 22 different cancers and kills about 8 million people per year, yet roughly 1 billion people still smoke. Australia cut its adult smoking rate from 35% in 1980 to about 11% in 2022, direct evidence that environmental disease falls when population exposure falls.

Principle 1: exposure is required

Unlike a genetic disease, which is present from conception, an environmental disease needs an external agent to start the process: a chemical carcinogen, radiation, or a toxic fibre. Remove the exposure and the disease does not occur. This is why lung cancer rates fell in countries that cut smoking through taxes, advertising bans and plain packaging.

Principle 2: dose and response

Risk rises with the cumulative dose, meaning how much of the agent and for how long, not simply whether exposure happened. Smoking dose is measured in pack-years: packs per day multiplied by years smoked. Twenty cigarettes a day for 40 years is a far larger dose than five a day for five years, and the lung cancer risk difference matches.

Why does more exposure mean more risk? Each exposure creates a small probability of a mutation in an exposed cell. Most damage is repaired, or the cell dies, but cancer needs several mutations in key genes within one cell line. More exposure means more mutations per year, so the required combination arrives sooner.

Principle 3: latency

Environmental diseases rarely appear straight after first exposure. Lung cancer usually emerges 20 to 30 years after a person starts smoking, and mesothelioma 20 to 50 years after asbestos exposure. Latency is the time needed for enough mutations to accumulate, which is why people often fail to connect a diagnosis with an exposure decades earlier.

Dose and latency also explain how epidemiologists work. Studies measure cumulative exposure in units such as pack-years, sun-exposure hours or years in an asbestos trade, then follow cohorts for decades, because following them for only a few years would miss diseases still inside their latency period. You will reuse this reasoning in L12 to L14.

Repeated ultraviolet (UV) radiation is absorbed by DNA in skin cells. The energy can join two neighbouring bases together, so the DNA is damaged. If this damage is not repaired before the cell divides, the change becomes permanent and cell-cycle control can fail.

Tobacco smoke is the most studied environmental carcinogen: a mixture of over 7,000 chemicals, more than 70 of them known carcinogens such as benzopyrene, nitrosamines and formaldehyde. It drives three separate disease pathways, and each has its own molecular mechanism. Exams reward students who keep the three mechanisms distinct.

Pathway 1: lung cancer

Carcinogens such as benzopyrene cross the bronchial epithelium and are activated into reactive forms that bond covalently to DNA, forming DNA adducts. Replication across an adduct produces errors, and mutations accumulate in the KRAS oncogene and the TP53 tumour suppressor. Once cell-cycle checkpoints fail, the cell line divides uncontrollably. About 85% of lung cancers occur in smokers or ex-smokers.

Pathway 2: COPD

Smoke irritants trigger chronic airway inflammation. Recruited macrophages and neutrophils release elastase, an enzyme that digests the elastin in alveolar walls, so gas-exchange surface is lost and the lungs lose the elastic recoil that drives exhalation. This is emphysema. At the same time, mucus-secreting cells overproduce mucus that obstructs small airways, which is chronic bronchitis. Together they cause COPD, progressive and largely irreversible.

Pathway 3: cardiovascular disease

Smoke chemicals injure the endothelium lining blood vessels and provoke inflammation. Nicotine constricts vessels and raises heart rate and blood pressure, while carbon monoxide binds haemoglobin more tightly than oxygen, forming carboxyhaemoglobin and cutting oxygen delivery. Chronic endothelial damage promotes atherosclerosis: lipid plaques narrow the arteries and raise the risk of thrombosis, heart attack and stroke.

Smoking causes roughly 21,000 Australian deaths each year, the country's leading preventable cause of premature death. Rates have fallen from about 72% of adult men in 1945 to about 11% today, driven by taxes, public campaigns and the 2012 plain-packaging laws, a world first. Population exposure fell, and disease rates followed.

The same smoke mixture reaches non-smokers as second-hand smoke, and residue lingers on surfaces as third-hand smoke. The dose is lower, but the carcinogens are identical, which is why smoke-free laws in pubs, workplaces and cars carrying children cut exposure for people who never chose to smoke.

UV is a physical, not chemical, mutagen. UV-B (280 to 315 nm) photons are absorbed directly by adjacent thymine bases in skin-cell DNA, and the energy drives a photochemical reaction that welds the two bases into a thymine dimer. The dimer distorts the helix, blocks normal base pairing, and stalls DNA polymerase during replication.

From dimer to mutation

Nucleotide excision repair normally cuts dimers out and rebuilds the strand, and it is highly efficient. Trouble starts when exposure is intense or repeated: dimers form faster than repair can clear them, some persist through replication, and mutations with a characteristic CC to TT signature appear. In melanocytes, a mutation activating the BRAF oncogene (found in about 60% of melanomas) combined with loss of the CDKN2A tumour suppressor releases uncontrolled growth.

The Australian context

Australia has the world's highest melanoma rate, about 15,000 new cases a year, and two in three Australians will be diagnosed with some form of skin cancer by age 70. High UV index, a largely fair-skinned population and an outdoor culture all contribute. Tanning beds add concentrated exposure, emitting up to 2.5 times the UV of the midday Australian sun, and the IARC classifies them as Group 1 carcinogens.

Public campaigns such as SunSmart (slip, slop, slap) have run since the 1980s and have changed behaviour in younger Australians. Because skin cancer has a long latency, today's high incidence mostly reflects sun exposure accumulated decades ago, so the benefits of campaigns take years to appear in the statistics.

Darker skin carries more melanin, which absorbs some UV and lowers damage, but the protection is partial, never complete: no skin type blocks all UV, and tanning-bed users of every skin type accumulate dimer damage. Melanoma arises in melanocytes; basal and squamous cell carcinomas arise in keratinocytes through the same dimer mechanism with different gene targets.

Asbestos is a chemically inert, biopersistent mineral fibre, and its danger is physical. Inhaled fibres longer than about 5 micrometres cannot be fully engulfed by alveolar macrophages. The cells attempt phagocytosis, fail, and keep trying, a state called frustrated phagocytosis. For years they release reactive oxygen species and inflammatory signals around fibres the body cannot break down.

From fibre to mesothelioma

The reactive oxygen species damage DNA in nearby mesothelial cells lining the pleura, while chronic inflammation drives extra cell division that propagates copying errors. Over 20 to 50 years, mutations accumulate in tumour suppressors such as BAP1, NF2 and CDKN2A, and malignant mesothelioma can result. The extreme latency reflects slow damage accumulation in a tissue whose cells divide slowly.

Australia's asbestos legacy

Australia used asbestos heavily in fibro sheeting, roofing and insulation from the 1940s to the 1980s, and banned it only in 2003. Because latency runs to decades, mesothelioma cases from old exposures are still appearing; Australia records about 700 mesothelioma deaths a year, one of the world's highest rates. The ban did not remove fibres already lodged in lungs.

Asbestos and smoking interact synergistically on lung cancer. A non-smoking asbestos worker carries roughly 5 times the baseline risk, while a smoking asbestos worker carries 50 to 90 times, far above the sum of the separate risks. Two exposures can multiply each other, a key example of environment-environment interaction in the multifactorial model from L06.

An exposure can also change gene behaviour without touching the DNA sequence. In DNA methylation, a methyl group attaches to cytosine bases in a gene's promoter region; transcription factors can no longer bind, and the gene is silenced. Tobacco smoke can methylate the CDKN2A promoter this way, switching off the p16 tumour suppressor while leaving its sequence intact. The functional result matches a loss-of-function mutation.

The second mechanism: histone modification

DNA winds around histone proteins, and chemical tags on histone tails loosen or tighten that winding, changing how accessible genes are to the transcription machinery. One exposure can therefore shift the expression of many genes at once. Unlike most mutations, some epigenetic marks are reversible, which is one reason they attract research interest.

Why epigenetics matters

Epigenetics explains patterns mutation alone cannot: identical twins with the same DNA developing different diseases after different lifetimes of exposure, or the same exposure affecting people differently. In one study pattern, smokers carrying methylation of the p16 promoter had a fivefold higher lung cancer risk than smokers without it, direct evidence that an exposure can raise risk by altering expression, not sequence.

If smoking causes lung cancer, why do many lifelong heavy smokers never develop it, while about 15% of lung cancers occur in people who never smoked? The answer is that environmental disease is multifactorial. DNA-repair efficiency varies between people, a gene-environment interaction; immune surveillance destroys some damaged cells before they turn malignant; and which cells accumulate the critical mutations is partly chance.

The never-smoker cases point to exposures beyond cigarettes: radon gas accumulating in homes, second-hand smoke, urban air pollution and occupational carcinogens all deliver dose to lung tissue. Exposure raises probability, it never guarantees an outcome, and no exposure acts as the single cause on its own. Population-level risk stays predictable even when individual outcomes are not.

This framing also keeps the ethics straight. Exposure is shaped by workplace conditions, government policy, product access and addiction, not by choice alone, and latency means a disease can trace back to an exposure the person never controlled, including childhood exposures. Explaining risk as biology, without blaming the patient, is exactly what the evaluate questions in this lesson reward.