Causes of Cancer: Environmental

Question 1

latency

Answer 1

• time between exposure to carcinogenic agent and the appearance of the tumour
• individuals exposed earlier in life are more cancer-prone than if exposed in later years
• thyroid and breast cancer incidence higher in those exposed <15 yrs but unchanged in those >50 yrs

Question 2

tobacco and cancer

Answer 2

• largest preventable cause of death in world
• > 25% of all cancer deaths
• 3 in 10 cancer cases causes by active or passive smoking
• linked to MANY cancers, ie. lung, bladder, pancreatic, mouth and neck cancers
• smoking contains BENZENE and ACROLEIN

Question 3

acrolein

Answer 3

• smoking
• herbicide in water systems
• emissions from fuel combustion
• high temperature roasting and deep fat frying
• endogenously

Question 4

smoking + drinking

Answer 4

• increased risk for mouth, voice box, oesophagus for smokers who drink more than 2 drinks a day

Question 5

diet and lifestyle

Answer 5

• inactivity linked to increased risks of colon and breast cancer
• obesity strongly linked with breast cancer in older women, cancers of endometrium, kidney, colon and oesophagus
• lack of fibre linked to CRC
• inactivity and obesity account for 25-30% cancers
• various microbiomes in gut have impacts on cancer

Question 6

alcohol

Answer 6

heavy drinkers induce cancers of mouth, throat, oesophagus, liver and breast

Question 7

UV light

Answer 7

• COMPLETE carcinogen: promotor AND initiator
• skin damage and melanoma
• causing pyrimidine dimers and other DNA damage (NER pathway)
• UVB most dangerous
• XP NER pathway defect, increases risk of skin cancer and other solid malignancies
• at least 9 genes involved in XP
• UV also affects local and systematic immune function in skin

Question 8

pesticides

Answer 8

• over 900 active ingredients and at least 20 are likely carcinogens
• many banned or restricted: ethylene oxide, DDT, nitrofen, lindane
• workers with pesticide exposure have high levels of blood/lymph cancers as well as cancers of the lip, stomach, lung , brain, prostate, melaoma

Question 9

viruses

Answer 9

• HPV: cervical and anal cancer, alongside head and neck
• Hep B/C: liver cancer
• EBV: lypmphoma -> karposis syndrome

Question 10

oestrogens

Answer 10

• endometrial cancer increased by HRT/oral contraceptives
• increased risk of breast cancer BUT reduced risk of colon cancer
• progesterone and oestrogen together may reduce cancer risks but evidence shaky
• DES banned due to increasing risk of breast cancer and cervical/vaginal cancers in newborns
• tamoxifen: increased risk of endometrial cancer but used to treat ER+ breast cancer

Question 11

medical drugs

Answer 11

• chemos can treat and cause cancers
• usually increase secondary cancers like leukaemias
• immunosuppressants associated with lymphomas
• NSAIDS/aspirin shown to reduce colon cancer risk

Question 12

solvents

Answer 12

linked to cancers, but only likely to be cancer causing not official carcinogens
- EXCEPT BENZENE

Question 13

benzene

Answer 13

• known to cause leukaemia in humans
• use in pesticides has been banned
• most exposure comes from petrol, and inhaling contaminated air, btu some from cigarette smoking

Question 14

dioxins

Answer 14

• generally exposed to low levels of TCDD, found in dairy products, fish and meat
• don’t break down so may build up over time

Question 15

polycyclic aromatic hydrocarbons (PAHs)

Answer 15

• burning carbon-containing compounds releases these
• pyrene and benzopyrene
• diesel exhaust

Question 16

fibres, fine particles and dust

Answer 16

• asbestos: small fibres, cause mesothelioma, greatest risk with those who smoke
• oxidative stress theory: phagocytic cells egulf fibres abd produce free radicals
• chromosome tangling theory: asbestos fibres damage chromosomes when cells divide
• theory of adsorption: in vivo fibres concentrate/accumulate proteins/chemicals including components of cigarette smoke
• silica dusts and ceramic fibres associated with increased risk of lung cancer
• wood dust associated with nasal cavities and sinuses cancers

Question 17

metals

Answer 17

• heavy metals
• oxidative stress (ROS, free radicals) in cells
• arsenic (skin, lung, liver, kidney), cadmium (lung), chromium (lung) and nickel (lung, nasal cavity)
• exposed via emissions, food, water
• HOMEOSTASIS as required for normal function

Question 18

fungi toxins

Answer 18

• grains and peanuts that fungi grow on
• aflatoxins produced
• increase liver cancer

Question 19

ionising radiation

Answer 19

• x-rays/gamma-rays
• can cause DNA damage
• alpha particles most dangerous (blast DNA apart), cause most damage BUT least penetration power
• produced from radioactive decay
• RT used in cancer treatment but can damage healthy cells, causing cancer

Question 20

Ataxia Telangiectasia

Answer 20

• AT
• genome instability or DNA damage response syndrome
• radiation hypersensitivity increased cancer risk
• lymphomas and leukaemias most likely cancers to be caused <20 yrs
• older adults susceptible to lymphoid and solid tumours
• carriers also have increased risk of cancers (breast and GI)

Question 21

detecting mutational signatures of environmental agents

Answer 21

• recent technology
• whole genome sequencing after exposure to specific agents
• can pinpoint where mutations occurred
• most act as promoters not initiators

Question 21

radon gas

Answer 21

• biggest environmental exposure
• dependent on where you live
• Cornwall, Aberdeenshire have higher levels than average
• product of uranium decomposition
• uranium -> radon -> polonium -> lung cancer due to increasing inhalation of alpha particle emitters