Cancer as an Environmental Disease:Liver Cancer in Bangladesh

张誉馨 旷骏祥

AbstractAlthough cancer is considered a common human genetic disease， there has been no significant evidence showing that it is caused by DNA mutations. DNA mutations as drivers or passengers associated with cancer development have been described in many reports. In addition， it has been shown that environmental factors can induce cancer， and thus， cancer can be considered an environmental disease. Liver cancer has become prevalent in Bangladesh， most likely due to environmental pollution as the groundwater is naturally contaminated with toxic levels of arsenic. The harm caused by contamination has not been limited to liver cancer， as other cancer types have been reported. Moreover， in worst-case scenarios， intake of arsenic has even caused death. As arsenic is usually found in groundwater worldwide， anyone can be affected. However， intake of only a tiny amount is not considered poisonous. Bangladesh has been greatly suffering from arsenic contamination， and as a result， toxicity and cancer have become prevalent.

Keywords：Naturally; Arsenic; Liver Cancer; Bangladesh; Toxicity; Arsenite， Cytotoxicity， Genotoxicity

【中圖分类号】R969.4【文献标识码】B【文章编号】2095-6851（2019）02-243-01

1.Introduction

Many factors can affect a persons chances of developing a cancer， all of which involve genetic mutations， although the exact mechanisms differ with cancer type. Due to this， cancer can be considered a genetic disease. However， in many ways， it can also be considered an environmental disease as previous reports have shown that environmental factors cause at least two-thirds of all cancer cases. Environmental tobacco smoke is one of the most typical examples， accounting for almost one in three preventable cancer cases12. People working in industrial and agricultural occupations， who are exposed to chemicals such as pesticides， are more likely to have cancer. There are many natural environmental sources of cancer-causing substances as well. Radon gas， for example， is emitted from the ground in some places， and causes lung cancer. Arsenic is naturally found in some sources of water and is also carcinogenic. Bangladesh currently has one of the highest rates of arsenic-related diseases worldwide， which has reportedly led to some types of deadly cancer. Arsenic is a semi-metallic chemical found in groundwater， which causes adverse health effects in humans when swallowed， inhaled， or absorbed. The environmental roots of widespread arsenic poisoning and resultant surge in the rate of liver cancer and other forms of cancer show how critical environmental factors are to the development of cancer rather than strictly inherited genetic factors4. This article is based on previous studies and does not include any new studies of human or animal subjects.

1.1Cancer may be caused by environmental factors

These genetic changes happen in many different ways. Many are the result of errors that occur when cells divide， as they naturally do throughout the lifespan. They can also occur as a result of exposure to substances that damage DNA， such as the chemicals in tobacco smoke， radiation， and industrial chemicals. However， most reports have described the role of DNA mutations as drivers and passengers in cancer initiation and development， although no specific source has verified that cancer is primarily a genetic disease. Studies have reported DNA changes as causal events， and they have noted multiple factors that cause DNA mutations without necessarily causing cancer1. The mutated gene found in cancer is based on coincidental observations on the pattern of mutations in affected genes6. Therefore， it is justifiable to consider the gene likely to be the inducible factor of cancer development3. Some somatic mutations have been identified as passenger gene mutations， which are not involved in metastatic cancer activity and do not contribute to oncogenesis， as they are essentially neutral and just accumulate in somatic cells15. The primary sources of somatic mutations are environmental. Colorectal cancer is one of the deadliest cancers worldwide， and is commonly caused by environmental risk factors， such as dietary habit and lifestyle13. In addition， too much exposure to radon gas in the home， for example， can lead to genetic damage and cancer， and too much exposure to the ultraviolet rays of the sun is one of the leading causes of skin cancer. In fact， one study showed that about 65-90% melanomas are attributable to ultraviolet exposure7. Moreover， at least 75% of esophageal cancer （lung cancer） cases are caused by tobacco and alcohol. Thus， it may be more accurate to think of cancer as an environmental disease rather than a genetic one.

1.3Naturally Occurring Arsenic in Groundwater

Arsenic occurs naturally in an inorganic form. It is the 20th most common element in the Earths crust and is part of hundreds of minerals. Thus in certain places， arsenic is somewhat common， but is harmlessly bound to rocks and soil. The most common forms of inorganic arsenic are arsenite and arsenate. Both of these compounds have harmful and even fatal effects on human health after their ingestion. Arsenic accumulates in the body over time， increasing in concentration until it reaches high enough levels to start causing severe health problems including cancer. Since arsenic is a natural part of certain types of rocks， the weathering of those rocks can cause them to separate from the minerals they were bound to， which then enter the groundwater in the region of those rocks.

2 The arsenic groundwater crisis in Bangladesh

Bangladesh has been suffering from one of the most massive arsenic catastrophes in world history6. More than half of Bangladeshs population is facing the problem of arsenic contamination of groundwater. Since the arsenic groundwater crisis was discovered， thousands of people have been stricken by arsenic-induced disease known as arsenicosis. A total of 59 of Bangladeshs 64 districts have been affected by arsenic from the groundwater used by the residents for drinking. Groundwater is the primary source of drinking water for 97% of the people living in rural areas of Bangladesh， as well as many urban residents. Arsenic contamination of groundwater in the Deltaic region， particularly in the Gangetic alluvium of Bangladesh and part of West Bengal， has become one of the worlds most critical natural calamities2.

3Cause of crisis

Irrigation with contaminated water

Irrigation seems to be another significant factor in development of the crisis. Bangladesh relies heavily on its rice agriculture industry to feed its population. Therefore， it is possible to have adverse health hazards with arsenic exposure from food-chain contamination6. Generally， arsenic exists in plants roots and its content depends on the type of plants， type of soil material， and the amount of trace metal in the irrigation water. To ensure that rice crops are sufficiently watered， Bangladeshs farmers rely on irrigation， which extracts water from deep or shallow groundwater to spray it over large areas of ground8. According to Hugs research， arsenic accumulates in the roots and straws of plants， and arsenic content in rice depends on the type of plant and area where it grew. Therefore， there is a positive relationship between contaminated irrigation water and the arsenic amount in rice. Irrigation with contaminated water can cause arsenic to accumulate in rice， further spreading the poisoning， which means that people who eat food irrigated by contaminated wells are also at risk， not just those who drink from contaminated wells. Irrigation also spreads arsenic across the ground and introduces it to new areas. This may be one of the reasons that arsenic contamination has been slowly spreading since its discovery in 1993. Furthermore， there is about 60-70% of arsenic in concentration of the water irrigated to the soils， similar to contaminated influent water9. The trace amount of arsenic accumulates in the human body through contaminated crop consumption， which causes chronic severe health hazards such as skin， bladder， lung， and liver cancers11.

4Analysis

4.1Arsenic（III） causes hazards

Toxicity through arsenic absorption can have both cancerous and non-cancerous effects. Unfortunately， Bangladesh has mainly received harmful effects， particularly liver cancer. As （III） （trivalent As203） or arsenic trioxide is extremely poisonous3. Data on the amount of toxic dosage is not generally available， but the deadly amount of this oxide arsenic is 1-3 mg/kg. In a matter of an hour， the harmful effects of the substance can become apparent. In a more serious case of As （III） poisoning， multi-organ failure along with cardiac poisoning prolongation can occur. In addition to these two significant effects， other complications can manifest. For instance， an arrhythmia can lead to cardiac failure indicating that the affected person may be experiencing irregular heart rates. Also， the person may experience a too fast or too slow heartbeat. Although most of these cases are nonfatal， some instances can lead to cardiac collapse3. The effects also include renal and hepatic failure. In more severe cases， end-stage kidney disease can occur， which means that the disease is irreversible. When the kidney has stopped working， the body fills with more water and waste， which is known as uremia10， which can cause swollen hands and feet and other symptoms that include continually feeling tired and weak. Such a condition results from the lack of clean blood that is needed for the body to function correctly. Without proper medical treatment， seizures and coma can occur that may eventually lead to death10. As （III） poisoning can also cause hepatic failure or liver disease. This disease has two forms： acute and chronic. Acute liver disease develops quickly， and the patient can lose liver function within weeks or even less than a week. It can strike suddenly even in the absence of apparent symptoms. Chronic liver failure， on the other hand， progresses more slowly than the acute form， and associated symptoms can take months or years to manifest. In this condition， the liver becomes inflamed， prompting the formation of scar tissue. Over time， the process of replacing healthy tissues with scar tissues may cause liver failure. In most cases， this condition is caused by alcohol consumption; however， in rare cases， it is caused by poisoning from an arsenic compound， as has been observed in Bangladesh.

4.2Arsenic（V） causes hazardsAccording to Ratnaike （2003）， As （V） or the pentavalent form of arsenic is 60-fold less toxic than As （III）. As （V） is organic and generally non-toxic， but As （III） is the opposite. What makes As （III） more toxic is its ability to effortlessly unite with specific proteins that are carried into the cell. By contrast， As （V） does not possess that capability， and thus， cannot reach the cell. However， As （V） can reach the cell in the process that the arsenate is reduced to As （III）. Arsenate usually exists in the environment， particularly in drinking water. As （III） is generally considered more toxic than As （V）， while As （V） can pose health risks to humans. Arsenate can cause erythrocyte or red blood cell toxicity， in which case the arsenic compound can cause the cell to be deformed or change its shape. According to Winski and Carter， such abnormality can cause disorders in microcirculation and promote the development of ischemia and tissue damage. Microcirculation refers to the flow of blood in the bodys tiniest blood vessels. Ischemia， on the other hand， occurs when blood flow into the heart is inadequate. When this occurs， the heart is deprived of oxygen， and the reduced amount of blood flow can lead to partial or complete congestion of the coronary arteries. Sequentially， the condition can damage the heart muscle and reduce its ability to function. In more severe cases， sudden coronary artery congestion can cause a heart attack.

4.3Mechanism of arsenic poisoning

Cytotoxicity and Genotoxicity of Arsenic

Carcinogens such as arsenic have been researched for many decades， and have shown that long-term exposure to arsenic may lead to certain diseases such as skin， lung bladder， liver， and prostate cancers. Cytotoxicity is the quality of being toxic to cells， while genotoxicity is the quality of being toxic to genes. The most common genotoxic and cytotoxic health effects of arsenic are related to human lung cells， skin cells， and keratosis functionalities upon prolonged exposure. Some studies have also been performed on the Chinese hamster ovary to determine the effects genotoxic and cytotoxic effects of arsenic exposure5. Among the various layers of the human skin， the epidermis （also known as the epithelial layer） is comprised of dendritic cells， melanocytes， and keratinocytes. Arsenic is highly genotoxic to all three epithelial layers; arsenic genotoxicity is severe in dendritic cells during acute exposure， while arsenic cytotoxicity is high in melanocytes during acute exposure. Chronic exposure results in maximum arsenic genotoxicity in dendritic cells and high cytotoxicity in melanocytes. Thus， it is clear that arsenic is both cytotoxic and genotoxic. In a study by Xie14， the effects of arsenic cytotoxicity and genotoxicity on human lung cells were determined. Specifically， bronchial fibroblast cells were analyzed， and it was found that chromosomal damage in these cells were dependent on arsenic concentration. Along with fibroblast cells， epithelial cells were also analyzed and the comet assay technique was performed. The analytical results suggested that arsenic was cytotoxic and genotoxic to human lungs. It was also concluded that fibroblasts were more sensitive than epithelial cells.Most humans are exposed to organic derivatives of arsenic through food and mainly water. Arsenic's inorganic derivatives such as arsenate and arsenite biologically transform into methylated metabolites. A study of trivalent and pentavalent arsenic derivatives such as arsenate （As（V））， arsenite （As（III））， and the resultant data showed that arsenic in its trivalent （III） oxidation state was more cytotoxic than its pentavalent （V） oxidation state. Cell membrane penetration， which is the cause of arsenic genotoxicity， was found to be stronger in the trivalent oxidation state5.

5Conclusion

With the exception of certain rare types of familial cancers， in which inherited genetics play the main role in their development， inherited genetic factors only make minor contributions to increasing the risk of developing most forms of cancer. This has been demonstrated by the increased rates of liver cancer in areas where there are high environmental concentrations of arsenic. Human interactions with the environment can only explain its rates. In general， the environment is the primary cause for the development of the vast majority of cancers.

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