How do the environmental carcinogens affect our bodies?
How do the environmental carcinogens affect our bodies?
The majority of cancers result from a complex interaction between genetic factors and exposure to
environmental carcinogens. Most of these environmental triggers have been
identified using epidemiological studies which examine patterns of cancer distribution in patients of different age, sex, social class, geography, with different concomitant illnesses (Table 3.1). Sometimes these give strong pointers to the molecular or cellular causes of the disease, but for many solid cancers there is evidence of a
multifactorial pathogenesis even when there is a known principal cause.
The major physical carcinogen is radiation, which is ubiquitous in the environment and may be ionising or non- ionising. Ionising radiation is very high- energy radiation and includes gamma rays from cosmic radiation, isotope decay such as
alpha particles from radon gas, and X-rays from medical imaging. Non-ionising radiation has less energy and includes ultraviolet radiation from the sun and radiofrequency radiation from electronic devices.
High-frequency, high- energy ionising radiation damages cellular structures and DNA by displacing electrons from
atoms, resulting in an ion pair. Some tissues, such as bone marrow, thyroid and breast tissue, are particularly susceptible to the effects of ionising radiation.
Non-ionising radiation does not yield an ion pair but can still excite electrons, resulting in a chemical change to the target tissue. It is UVB that is the most significant in this
category. However, UVC has the most potent effect on DNA, but it is quickly absorbed in air, making its effects negligible. Distortion of the DNA double helix results from a thymidine dimer that produces covalent bonding of adjacent thymidine residues on the same DNA strand. This distortion is normally repaired by the nucleotide excision
repair (NER) pathway. Patients with xeroderma pigmentosum have
defects in this mechanism, resulting in UV-induced skin
malignancies. The incidence of cancers is greater in less pigmented populations because melanin absorbs UV radiation and acts to shield the dividing cells in the skin. Severe sunburn in youth is a
significant risk factor for the subsequent development of malignant melanoma.
Many chemicals can induce cancer and are referred to as carcinogens, which can act on three distinct steps of initiation, promotion and progression. Initiation requires replication of cells where repair of the chemically induced DNA damage
has failed, and a single exposure to a carcinogen may be sufficient. Promotion is a reversible process requiring multiple exposures, often with a dose-response threshold, which produces a selective growth advantage, usually without DNA mutation. Progression is irreversible and involves multiple complex DNA changes, such as
chromosomal alterations and morphological cellular changes, which are detectable with microscopy.
Many potent carcinogens are strong electrophiles that can accept electrons, such as vinyl chloride, aflatoxin, N-hydroxylated metabolites of azo dyes and alkyldiazonium ions from nitrosamines.
The chemical constituents of tobacco smoke are carcinogens and particularly increase the risk of lung, oropharyngeal, oesophageal and bladder cancers. However, associations exist with all cancers, with the exception of endometrial cancer for which
smoking appears to be protective. Ninety per cent of lung cancers are directly attributable to smoking, and mortality from lung cancer is 30- fold higher in smokers than in non-smokers. Inhalation of mainstream smoke is most associated with cancer, but passive smoking will increase risk significantly.
Infection makes the most significant contribution to the global burden of cancer, with
million cases of cancer (15%) per year (cervical, stomach, liver, bladder and lymphoma) due to infection. The association between virus
infection and cancer was first demonstrated in 1911 by Peyton Rous, studying the
development of sarcoma in chickens. Following HIV infection, the weakened immune system cannot respond to other viral carcinogens. In the presence of HIV, those infected with human herpes virus (HHV) 8 will develop Kaposi’s sarcoma and
Castleman’s syndrome. The majority of other herpes viruses have been implicated in cancers, most notably Epstein– Barr virus (EBV) in causing Hodgkin’s lymphoma or Burkitt’s lymphoma.
The papilloma viruses HPV 16, 18, 31 and 45
are major aetiological factors for the development of cervical cancer, and the hepatitis
B and C viruses are known causes of hepatocellular
carcinoma. The main parasitic infections linked to cancer are malaria associated with Burkitt’s lymphoma and schistosoma associated with various other cancers. Schistosoma japonicum has been linked to colorectal, hepatocellular and lymphoreticular cancers,
and schistosoma haematobium to bladder cancer. Chronic inflammation is thought to play a central role in both cases. Chronic bacterial infections such as tuberculosis have been linked to an increased risk of developing cancer.
Cancer can be induced by overproduction of endogenous hormones as well as exogenous substances as contained within the combined oral contraceptive pill (COCP) and hormone replacement therapy (HRT) (Table 3.2). Risk of breast cancer is related
to the duration of exposure to oestrogens, with risk increased by low parity, early
menopause and prolonged exposure to oestrogens by the use of HRT. The COCP does not increase risk as it is used at a time in the life cycle when oestrogen is naturally present. Ovarian cancer is related to the number of
ovulations, therefore the risk is increased by nulliparity but reduced by the COCP, reducing by 50% in those taking the COCP for 10 or more years. The risk of endometrial cancer in postmenopausal women is increased by using oestrogen-only HRT or tamoxifen.
Nutrition and lifestyle
Around 30% of all cancers and up to 70% of gastrointestinal (GI) malignancies are thought to be associated with poor nutrition, and obesity increases the risk of cancer, independent of quality of diet. Alcohol is
associated with cancers of the GI tract, liver, breast and ovary, possibly by causing oxidative stress and prolonged exposure to acetaldehyde, the main metabolite of alcohol. Patients with alcohol- induced liver cirrhosis are at increased risk of hepatocellular
carcinoma. Lifestyle changes can impact on risk; for example, the
risk of breast cancer in women of Far Eastern origin remains relatively low when they first migrate to a country with a Western lifestyle, but rises in subsequent generations to approach that of the resident population of the host country.