Cancer: How is Your Diet Responsible?
(Group 1) Carcinogens Present In Diet That You Consume
Ohh that tasty piece of processed beef is so yum and juicy and also group 1 carcinogen!!!
As per a report by WHO, cancer will claim 9.6 million lives globally this year (2018) with India’s share in it being 8.17%.
Another report by Lancet predicted that cancer is India’s second biggest killer after heart disease.
The Lancet report also tells that between 1990 and 2016 the number of cancer deaths in India increased by 112%. Incidence of cancer cases also increased by 48.7%.
As per the Indian Council of Medical Research (ICMR) data, India had 1.4 million cancer patients in 2016. This number is increasing steadily.
In 2016, breast cancer had become the most common cancer in India. The global burden of cancer is huge and is increasing steadily.
One woman dies of cervical cancer every 8 minutes in India.
We should not think that we can get away with it. Cancer has become an increasingly common disease with each one of us knowing someone close to have suffered it.
And research suggests that over 90% of cancer cases are due to poor lifestyle choices and hence preventable.
The International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), has evaluated the carcinogenicity of various substances and classified them on the basis of evidence.
In this blog, we would discuss the potential carcinogens found in our diet and how eating a certain type of food items may increase the chances of getting cancer. Especially if, your family has a history of cancer.
First, let’s get to know about cancer, and how exactly is it caused. We keep talking about cancer and its relation with diet, and other things without even understanding the biochemistry of cancer.
What is Cancer?
In the human body, cells keep dividing and older cells die and are replaced by newer cells. This is a regular process and is controlled by certain genes in the DNA.
When this process becomes uncontrollable and cells keep growing uncontrollably than it causes cancer.
Cancer is referred to a set of over a hundred of diseases in which cells keep dividing abnormally and uncontrollably. The new cells are not needed and old and damaged cells that should die keep surviving and dividing.
The uncontrollable cell division may lead to accumulation of a mass of tissue inside the body, called tumours.
The tumours can be of two types broadly, benign and malignant.
- Benign tumours are the ones, which remain at their place of inception and don’t affect, and spread into nearby areas. Benign, tumours once removed don’t generally grow back.
- Cancerous tumours are generally malignant. They can invade nearby tissues and also travel to the distant body parts through the blood or the lymph system. Malignant tumours might grow back after removal.
Now, let’s understand the genetic breakdown.
Genetic Breakdown of Cancer
Cancer is caused by a malfunctioning in genetic makeup responsible for cell division either due to heredity or due to environmental causes.
The genetic changes that cause cancer can be inherited from parents. Although, inheriting such genes doesn’t ensure that cancer will be manifested.
The genetic changes may also arise during a person’s lifetime due to as errors that occur as cells divide or because of damage to DNA caused by certain environmental causes/exposures.
Cancer-causing environmental exposures include substances, such as the chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun, chemicals in the food like processed meat.
The genetic malfunctioning is triggered under certain environmental influences like diet, obesity, age, lifestyle, alcohol, and smoking etc and cancer manifests.
Each person with cancer has a unique combination of genetic changes.
Cancer cells have more mutations and genetic changes, in DNA, compared to normal cells. Some of these changes might be the result of cancer not the cause of it.
Genetic Changes Causing Cancer
The genetic manipulations that contribute to cancer tend to affect three main types of genes
- Proto-oncogenes
- Tumour suppressor genes, and
- DNA repair genes.
These changes are sometimes called “drivers” of cancer.
Proto-oncogenes: These genes play an instrumental role in normal cell growth and division. When these genes are damaged, altered or tampered with in certain ways making it more active than normal, the cell starts dividing uncontrollably.
They might become cancer-causing genes (oncogenes) allowing cells to grow when not needed and letting old and damaged cells survive when they should not.
Tumor Suppressor Genes: These genes also involved in controlling cell division.
When tumor suppressor genes are alterted or damaged in anyway, inside a cell, the cell may divide and grow in an uncontrolled manner and might cause cancer.
DNA repair genes: These genes are involved in fixing and restoring the damaged DNA.
Cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous.
Generally, when a gene in DNA is altered, the DNA repairs to it or instructs the cells to kills itself.
In our bodies, cancerous cells are produced and killed daily by the immune system. When the immune system is not able to detect and kill these cells and they keep multiplying this is how the cancer is caused.
Biology of Cancer
When the cancerous cells start to grow rapidly due to altercation of one or multiple genes, then they form a tumour, as we discussed in the blog earlier.
Metastasis: The tumour eventually develops its own blood supply. Like normal cells, cancer cells do not adhere well to each other and hence break away to enter the nearest blood vessel. This is how these cancerous cells reach other parts of the body and infect them also with cancerous cells.
This process is known as Metastasis.
It is also called stage IV for a lot of cancers. The metastatic cancer cells are like a primary cancer cell from the place of origin. That’s how doctors get to know, that cancer cells have spread from another part of the body.
Liver, brain, lungs and bones are major metastasis sites. Lymph system can also be a target under Metastasis.
Metastatic cancer cells from breast reaching lungs would be metastatic breast cancer, not metastatic lung cancer.
The name if as per the origin of cancer cells.
The ability of cancer cells to reach different parts of the body and infect healthy cells in the reason it is so darn dangerous.
Cancer cells spread through the body in a series of steps. These steps include:
- Invading and spreading to nearby normal tissue.
- Entering lymph and blood circulation through the walls of nearby lymph nodes or blood vessels.
- Reaching distant body parts and penetrating the tissues through the lymphatic system and bloodstream.
- Growing and dividing in this tissue until tiny tumour forms.
- New blood vessels come up, which create a blood supply that allows the tumour to continue growing.
Generally, spreading cancer cells die at some place in this process. But some of them are able to form new tumours in other parts of the body when conditions are favourable.
Metastatic cancer cells can also remain inactive at a distant site for many years before they begin to grow again, if at all.
Not all tumours are cancer.
Difference Between Normal and Cancer Cells
- Growth -Normal cells stop growing when enough cells are present, whereas cancer cells don’t.
- Communication -Cancer cells don’t interact with other cells as normal cells do. They don’t respond to signals which tell cells to die.
- Cell repair and cell death -Normal cells get repaired or die after getting old or damaged. Whereas, cancer cells are either not repaired or do not undergo apoptosis.
- Stickiness -Normal cells adhere to each through adhesive secretion that makes them stick together. Cancer cells don’t make these substances, and they can move inside the body through the lymph system and bloodstream to distant regions in the body.
- Appearance - Normal cells are more uniform and homogeneous in nature. Cancer cells often exhibit much more variability in cell size and shape. The nucleus is bigger and darker. The nucleus of cancer cells contains excess DNA and has an abnormal number of chromosomes that are arranged in a disorganized fashion.
- Maturation -Normal cells mature but cancer cells don’t. They divide rapidly before these cells are fully mature, and remain immature. The degree of maturation of cells corresponds to the “grade” of cancer. Cancers are graded on a scale from 1 to 3 with 3 being the most aggressive.
- Evading the immune system -Normal cells are removed by the immune system when they are damaged. But cancer cells are able to evade the immune system by escaping detection or by secreting chemicals that inactivate immune cells that come to the scene.
- Functioning -Normal cells perform their functions whereas cancer cells are generally dysfunctional.
- Energy Source - Normal cells get most of their energy through a process called the Krebs cycle, in the form of ATP. Normal cells produce most of their energy in the presence of oxygen, cancer cells produce most of their energy in the absence of oxygen.
- Mortality -Normal cells are mortal, they grow old and die. In normal cells, there is a substance called telomeres that that holds DNA together at the end of the chromosomes. Every time a cell divides, the telomeres get shortened. A cell can no longer divide when telomeres become too short and the cell dies. In cancer cells, an enzyme called telomerase works to lengthen the telomeres so that the cell can divide indefinitely essentially becoming immortal.
Now, let’s get to know the role diet can play in causing cancer.
Carcinogens in Food
Cancer is a major public health issue worldwide. Cancer is the leading cause of mortality in Canada and the second leading cause of mortality in the USA.
Only 5%–10% of cancers are attributed to inherited genetic defects. Remaining 90%–95% of all cancers cases have their roots in either environmental or lifestyle factors.
There is a direct relationship between diet and an increased risk of cancer.
As per estimations, diet accounts for 35% of all cancer risk.
Hence, most of the cancer cases are preventable. Just by abiding in healthy habits, lifestyle and dietary patterns, we can decrease incidences of cancer and decrease the global burden.
Now, we will study some carcinogens found in food items.
Carcinogen:
A carcinogen is defined as an agent that increases the incidence of neoplasms ( new and abnormal growth of tissue in a part of the body) compared with the incidence of inappropriate controls in a defined test organism.
There are two important complementary programs exist for the classification of exposures posing a carcinogenic risk to humans.
- US National Toxicology Program (NTP) produces the Report on Carcinogens. This report is biennial.
- The International Agency for Research on Cancer (IARC), the cancer research arm of the World Health Organization (WHO) produces IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.
There are primarily four types of potentially carcinogenic compounds that have been examined.
- Natural products that may be present in food and are unavoidable. Like, the process of creating salted fish produces carcinogens which are unavoidable.
- Natural products that might be avoided such as the contamination of grain with the carcinogenic fungal metabolite aflatoxin.
- Anthropogenic chemicals may be present in food. Like, 2,3,7,8-tetracholordibenzo-p-dioxin (TCDD) has been produced during the manufacture of chlorinated hydrocarbons. It contaminates the environment and accumulates in certain foodstuffs.
- Anthropogenic chemicals intentionally added to foods, such as saccharin or food colouring.
Let’s discuss the Group 1 carcinogens as per IARC’s classification. Group 1 carcinogens have significant evidence supporting their carcinogenic behaviour. This classification is based on strength of evidence not on strength of carcinogenic behaviour. Hence, the substances in the same category don’t possess an equal level of threats.
Processed meats: On 26 Oct 2015, IARC declared processed meat as group 1 carcinogens.
Any meat that has been preserved by adding chemical preservatives, curing, salting or smoking, fermenting or transformed using any other method comes in the category of processed meat.
Examples are bacon, sausages, hot dogs, pepperoni, prosciutto, beef jerky and salami etc.
Carcinogens might get formed during the processing of processed meat by various methods such as curing and smoking.
Bacteria in the human digestive tract transform nitrates and nitrites used for curing to N-nitroso compounds, some of which are potentially carcinogenic.
Cooking red meat at high temperatures like barbecuing can produce heterocyclic aromatic amines and polycyclic aromatic hydrocarbons which are also known or suspected carcinogens.
N-nitroso compounds, haem iron and heterocyclic aromatic amines present in meat have been identified as part of the mechanism linking meat consumption and cancer formation.
The IARC concludes that each 50g portion of processed meat consumed daily can increase the risk of colorectal cancer by 18%.
Reducing processed meat consumption reduces consumption of salt (sodium) which also has health benefits.
Salted fish (Chinese style): Methods employed to produce salted fish in several parts of Asia result in the production of carcinogens. Several potential carcinogens have been identified in chinese salted fish including N-nitrosodimethylamine, other N-nitroso compounds 20.
Studies have demonstrated an increased risk of nasopharyngeal (The upper part of the pharynx, connecting with the nasal cavity above the soft palate) carcinoma in subjects consuming larger amounts of Chinese-style salted fish.
Nasopharynx cancer or nasopharyngeal carcinoma (NPC) is the most common cancer
The consistency of evidence led IARC to classify these preserved fish as a Group 1 carcinogen. There is limited evidence linking salted fish to increased risk of stomach and esophageal cancer as well.
Fish are rich sources of secondary and tertiary amines, and nitrate and possibly nitrite occur in the crude salt used to pickle them.
N-nitroso compounds are formed during the preparation of salted fish. Several factors like, levels of nitrites and nitrates in crude salt, those of nitrogen oxide in the air, the growth of nitrate-reducing bacteria and pH, may affect the levels of N-nitroso compounds (group 1 carcinogens).
These two mechanisms are not mutually exclusive.
N-Nitroso compounds can also be formed after ingestion of foods by chemical nitrosation under acidic conditions in the stomach during digestion.
There are researches and studies that confirm that salted fish contains high concentrations of precursors of N-nitroso compounds which are carciongenic.
Consumption of salted fish in Chinese populations has also been associated with an increased risk for cancer of the lung, brain, and prostate.
Aflatoxins: Aflatoxins are a class of toxic metabolites produced by certain species of fungi. Aflatoxins are heat-resistant and can withstand exposure to normal cooking temperatures. Aflatoxins are best known for their potential in causing liver cancer and due to sufficient evidence they are put in group 1 by IARC.
A number of different specific chemical entities make up the class aflatoxins and they are generally present in food as mixtures.
Naturally-occurring aflatoxins, include aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2.
Aflatoxin B1 is the most common, the most toxic and the most potent when it comes to causing liver cancer in human.
Aflatoxins G1, M1, B2, G2 are in order of decreasing strength in terms of causing cell mutations.
Aflatoxins M1 and M2 are mostly found in milk and milk products.
Aflatoxins are generally found in tropical regions of the world. The high humidity, high temperature of the environment, coupled with inappropriate handling and storage of crops after harvest in developing countries, cause them to be more commonly found in various crops like peanuts, maize, cereals, cottonseeds, tree nuts and some spices etc.
When aflatoxins B1 and B2-contaminated crops are fed to cows, they are converted to the aflatoxins M1 and M2 respectively and can be found mainly in milk, but also in the liver and kidneys.
IARC has classified all naturally occurring aflatoxins to be carcinogenic and aflatoxin M1 to be possibly carcinogenic to humans.
Research also suggests that effect of aflatoxin B1 in causing cancer is stronger in people carrying hepatitis B virus or hepatitis C virus.
Aflatoxins cause cell mutations in liver and the effect is found to be strongest in aflatoxin B1 than in aflatoxins G1, G2 and B2.
Some researches in animals have found association that Alfatoxins possibly affect the immune system and impair growth. Cases of acute aflatoxin poisoning have also been noticed to happen sporadically in developing countries.
Proper agricultural practices can help reduce pre-harvest aflatoxin contamination.
During harvesting, crops should best be harvested at maturity and harvested crops should then be dried as quickly as possible. Damaged products should be removed as much as possible.
The crops should then be stored at proper temperature and humidity to minimize mould growth.
Consumers should store food under dry and cool condition. Consumers should discard food with signs of mould infestation.
Aflatoxins are found in various cereals, oilseeds, spices, and nuts. Aflatoxins contamination of wheat or barley is common. It happens due to inappropriate storage. In milk, aflatoxins is generally at 1–6% of the total content in the feedstuff .
Consumption of aflatoxins contaminated foods such as milk and milk products, eggs, meat and meat products also infects humans with alfatoxins.
Dioxins and dioxin-like PCBs: Dioxins and dioxin-like substances , including Polychlorinated biphenyls (PCBs), collectively called as (DLCs) are persistent organic pollutants and bioaccumulate in food chains through various man made and natural sources.
DLCs are byproducts of various industrial processes, such as smelting but still above 90% of dioxin exposure in humans comes through consumption of contaminated food.
For last two centuries these compounds have been exclusively generated by human activities.
In 2008 contamination of the Irish pork supply with dioxins resulted in an large scale international recall of all Irish pork products.
TCDD or 2,3,7,8-tetrachlorodibenzo-p-dioxin is the prototype these structurally-related compounds and agents called DLC.
These group of agents serve as ligands of the aryl hydrocarbon receptor (Ahr). Studies on different animal species have demonstrated the carcinogenic potential of TCDD in producing tumors in liver, thyroid, the upper aerodigestive tract, and skin.
Adverse health effects of dioxins exposure in humans are diverse. Dioxin exposure in humans may cause cardiovascular disease, diabetes, cancer, porphyria, endometriosis, early menopause, reduced testosterone, altered immunologic response, and altered metabolism etc.
Fat deposits from animals exposed to environmental and feed sources of DLCs are reservoirs of DLCs. These fat deposits may be directly introduced to the human population through foods of animal or aquatic origins or by the use of their fats in processed-food preparation, or indirectly through the recycling of animal- and aquatic-origin fats in feed.
Hence, consumption of animal fat in form of fish, shellfish, meat or milk related products is biggest source of human exposure to dioxins some of which are extremely toxic and group 1 carcinogens causing cancer in liver.
Alcoholic Bevarages: All types of alcoholic beverages, whether they are fermented or further distilled are known to cause cancer in humans with sufficient evidence and hence put in group 1 by IARC and NTP both.
Studies on animals have shown that ethanol itself is not carcinogenic enough. This leads to the hypothesis that other contaminants in alcoholic beverages or ethanol metabolites like acetaldehyde are responsible for these effects. The solvent action of ethanol may be relevant for co-carcinogens either in the beverages or in other dietary components.
Myraid of epidemiologic studies with consistency have found an association between regular alcoholic consumption and cancers of the mouth, pharynx, larynx, and esophagus, and possibly the breast and liver.
The cancer risk from alcohal has been found to be dose-dependent. Numerous studies have found direct correlation of cancer risk from alcoholic beverages with tobacco consumption.
In comparison with non drinkers consumption of about 50g of alcohol daily will increase the risk of the above cancers two to three times.
Another research in women has found that daily consumption of 50g of alcohol will increase the risk of breast cancer 1.5 times when compared with non-drinkers.
Drinking alchohal also expose drinkers to acetaldehyde another carcinogen. It is formed during alcohol fermentation and converted inside the body after alcohol consumption.
The IARC has classified acetaldehyde associated with alcoholic consumption as carcinogenic to humans (Group 1 agent).
Acetaldehyde is especially harmful for up to 30% of the East Asian populations. Because east asians have only about 10% of the enzyme activities that breakdown acetaldehyde, due to a genetic condition.
This leads to a higher risk of alcohol-related cancers in this demographic (east asian) when compared with the rest of the population.
Some studies suggest that moderate consumption of alcohal might have some health benefits but evidences are controvertial and insufficient. So if you want to keep your heart and body healthy, healthy lifestyle with minimum or no consumption of alochoal is advised.
Tobacco: Products made from dried tobacco leaves, are cigarettes, cigars, and puffs. Other chemicals are added for flavour. The smoke that comes from combustion of these products is a complex mixture of almost 4000 types of different chemicals.
At least 70 of these chemicals in the smoke are known carcinogens.
Nicotine, the addictive drug in tobacco is one of the harshest chemicals in tobacco smoke.
Others are Hydrogen cyanide, Formaldehyde, Lead, Arsenic, Ammonia, Radioactive elements, such as uranium, Benzene, Carbon monoxide, Nitrosamines, Polycyclic aromatic hydrocarbons (PAHs).
Arsenic, Benzene, Benzo[a]pyrene, Cadmium, Chromium (Hexavalent), Formaldehyde, 4-(N-Methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), NickelN’-Nitrosonornicotine (NNN) are some of the known group 1 carcinogens in tobacco smoke.
Many of these substances are known carcinogens, whereas some can cause cardiovascular diseases, lung disease, and other health related problems.
Tobacco smoke contains radioactive elements that might come from the fertilisers and other chemicals used for cultivation of tobacco. During smoking these radioactive elements enter our lungs and that is one of the major reasons cigarattes can cause cancer.
Smokeless tobacco products like snuff and chewing tobacco are not burned like cigarettes or cigars. But these smokeless tobacco products are not safe either.
They also contain cancer-causing agents, such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons (PAHs). These carcinogens are absorbed through the mouth. This might be the reason several types of cancer are linked to the use of smokeless tobacco. Smokeless tobacco also contains radioactive substances.
Snus a type of moist snuff that does not require spitting. It generally has lower levels of nicotine and TSNAs than conventional moist snuff brands, but can still be addictive and has been linked to some types of cancer.
There are some of the mainstream carcinogens that most of us keep consuming through our diet and can be easily avoided. Most of these carcinogens are not just cancer-causing they are associated with multiple types of health risks.
Summary
Cancer is a big global issue with deaths and cases rising steadily over the last couple of decades. The global expense of cancer is also rising exponentially.
In India, it is the second biggest cause of mortality after heart diseases. But the good news is 90–95% of cases of cancer are preventable because they are caused by environmental and lifestyle influences.
Cancer is caused by a genetic malfunctioning in DNA responsible for controlled cell growth and DNA. Studies suggest that 5–10% of such genetic malfunctioning is caused by heredity and 90–95% is acquired in the lifetime due to a person’s persistent exposure to certain carcinogens.
The genetic manipulations that contribute to cancer are generally associated with the following three genes.
- Proto-oncogenes
- Tumour suppressor genes,
- DNA repair genes.
Cancerous cells can accumulate in body forming large masses of malignant tumours, which can travel to other parts of the body through lymph and bloodstream, infecting other body parts also. This is called Metastasis.
IARC the cancer research arm of WHO has an extensive classification of substances based upon the evidence of their exposure causing cancer to humans and animals. Some of the major group 1 carcinogen (substances with sufficient evidence for causing cancer) by IARC are:
- Processed Meat: Examples are, bacon, sausage, salami etc. The IARC concludes that each 50g portion of processed meat consumed daily can increase the risk of colorectal cancer by 18%.
- Chinese Salted Fish: Several potential carcinogens have been identified including N-nitrosodimethylamine, other N-nitroso compounds 20 in Chinese Salted Fish. Studies have demonstrated an increased risk of nasopharyngeal carcinoma in subjects consuming larger amounts of Chinese-style salted fish.
- Aflatoxins: Aflatoxins cause cell mutations in the liver and the effect is found to be strongest in aflatoxin B1 than in aflatoxins G1, G2 and B2. Aflatoxins are found in various cereals, oilseeds, spices, and nuts. Aflatoxins contamination of wheat or barley is common. It happens due to inappropriate storage. In milk, aflatoxins are generally at 1–6% of the total content in the feedstuff.
- Dioxins and dioxin-like PCBs: DLCs are byproducts of various industrial processes, such as smelting but still above 90% of dioxin exposure in humans comes through consumption of contaminated food from animal foods like milk, milk products, fish, shellfish and meat etc.
- Alcohol: In comparison with non-drinkers consumption of about 50g of alcohol daily will increase the risk of the above cancers two to three times. The situation becomes worse for smoker and drinkers.
- Tobacco: Arsenic, Benzene, Benzo[a]pyrene, Cadmium, Chromium (Hexavalent), Formaldehyde, 4-(N-Methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), NickelN’-Nitrosonornicotine (NNN) are some of the known group 1 carcinogen in tobacco smoke. Smokeless tobacco is less dangerous but it also contains various group 1 carcinogen.
Hence, people who want to live a healthy life and want to mitigate their chances of getting cancer should remove or at least minimise these things from their life.
Following lifestyle patterns can help you fight cancer:
- Stopping or minimising consumption of alcohol and tobacco.
- Stopping or minimising consumption of processed meat.
- Minimising consumption of all kinds of animal fat and replacing them with vegan options (coconut milk, almond milk etc).
- Incorporate more seasonal raw vegetables and fruits in your diet.
- Having a more well-rounded diet to minimise exposure of any carcinogen from one kind of food item and being very conscious of the sources of your food items.
- Avoid food item cooked at a high temp.
- Keep yourself physically active and do regular physical activities.
- Give your body proper sleep and rest. Don’t overwork yourself.
- Avoid consuming polluted and contaminated water.
A healthy lifestyle can help you live a healthier, longer and more peaceful life. It can save you from chronic diseases like cancer, diabetes, lung problems and other cardiovascular diseases etc.
Happy healthy eating to all.
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Next blog would be on antibiotics contaminants in poultry.
References
https://academic.oup.com/jnci/article/105/9/616/986948
https://www.ncbi.nlm.nih.gov/pubmed/8395546
https://bmjopen.bmj.com/content/9/1/e023625
https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(15)00444-1.pdf
https://www.npr.org/sections/thesalt/2015/10/26/451211964/bad-day-for-bacon-processed-red-meats-cause-cancer-says-who
https://www.iarc.fr/wp-content/uploads/2018/07/pr240_E.pdf
https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/cooked-meats-fact-sheet
https://www.who.int/news-room/fact-sheets/detail/dioxins-and-their-effects-on-human-health
https://www.cancer.gov/about-cancer/understanding/what-is-cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515569/
https://www.cancer.org/cancer/cancer-causes/general-info/known-and-probable-human-carcinogens.html
https://www.ncbi.nlm.nih.gov/books/NBK304384/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240007/
https://www.canada.ca/en/health-canada/services/publications/healthy-living/carcinogens-tobacco-smoke.html
