Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms
TL;DR: Evidence that strongly supports causative mechanisms for genotoxicity and carcinogenicity of these substitute products, including gutkha and pan masala, are strongly implicated in the recent increase in the incidence of oral submucous fibrosis is reviewed.
Abstract: In south-east Asia, Taiwan and Papua New Guinea, smoking, alcohol consumption and chewing of betel quid with or without tobacco or areca nut with or without tobacco are the predominant causes of oral cancer. In most areas, betel quid consists of a mixture of areca nut, slaked lime, catechu and several condiments according to taste, wrapped in a betel leaf. Almost all habitual chewers use tobacco with or without the betel quid. In the last few decades, small, attractive and inexpensive sachets of betel quid substitutes have become widely available. Aggressively advertised and marketed, often claimed to be safer products, they are consumed by the very young and old alike, particularly in India, but also among migrant populations from these areas world wide. The product is basically a flavoured and sweetened dry mixture of areca nut, catechu and slaked lime with tobacco (gutkha) or without tobacco (pan masala). These products have been strongly implicated in the recent increase in the incidence of oral submucous fibrosis, especially in the very young, even after a short period of use. This precancerous lesion, which has a high rate of malignant transformation, is extremely debilitating and has no known cure. The use of tobacco with lime, betel quid with tobacco, betel quid without tobacco and areca nut have been classified as carcinogenic to humans. As gutkha and pan masala are mixtures of several of these ingredients, their carcinogenic affect can be surmised. We review evidence that strongly supports causative mechanisms for genotoxicity and carcinogenicity of these substitute products. Although some recent curbs have been put on the manufacture and sale of these products, urgent action is needed to permanently ban gutkha and pan masala, together with the other established oral cancer-causing tobacco products. Further, education to reduce or eliminate home-made preparations needs to be accelerated.
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TL;DR: Various mechanisms by which NO acts in different cancers such as breast, cervical, gastric,colorectal, and head and neck cancers are addressed and its novel therapeutic applications for cancer prevention and treatment are discussed.
Abstract: Nitric oxide (NO), is a ubiquitous, water soluble, free radical gas, which plays key role in various physiological as well as pathological processes. Over past decades, NO has emerged as a molecule of interest in carcinogenesis and tumor growth progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both tumoricidal as well as tumor promoting effects which depend on its timing, location, and concentration. NO has been suggested to modulate different cancer-related events including angiogenesis, apoptosis, cell cycle, invasion, and metastasis. On the other hand, it is also emerging as a potential anti-oncogenic agent. Strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain are being investigated. However, further validation and experimental/clinical trials are required for development of novel strategies based on NO for cancer treatment and prevention. This review discusses the range of actions of NO in cancer by performing an online MEDLINE search using relevant search terms and a review of the literature. Various mechanisms by which NO acts in different cancers such as breast, cervical, gastric,colorectal, and head and neck cancers are addressed. It also offers an insight into the dichotomous nature of NO and discusses its novel therapeutic applications for cancer prevention and treatment.
482 citations
Cites background from "Alert for an epidemic of oral cance..."
...The high incidence of oral cancer and oral pre-cancer has been linked with habits of tobacco chewing and smoking [78,79]....
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01 Jan 2012
TL;DR: PReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl
Abstract: pReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl hAbIts And IndooR CombustIons; ChemICAl Agents And RelAted oCCupAtIons. thIs Volume 100f CoVeRs ChemICAl Agents And RelAted oCCupAtIons, speCIfICAlly 4-AmInobIphenyl, benzIdIne, dyes metAbolIzed to benzIdIne, 4,4’-methylenebIs(2-ChloRoAnIlIne), 2-nAphthylAmIne, oRtho-toluIdIne, AuRAmIne And AuRAmIne pRoduCtIon, mAgentA And mAgentA pRoduCtIon, benzo[A]pyRene, CoAl gAsIfICAtIon, oCCupAtIonAl exposuRes duRIng CoAl-tAR dIstIllAtIon, CoAl-tAR pItCh, Coke pRoduCtIon, untReAted oR mIldly tReAted mIneRAl oIls, shAle oIls, soot, As found In oCCupAtIonAl exposuRe of ChImney-sweeps, oCCupAtIonAl exposuRes duRIng AlumInIum pRoduCtIon, AflAtoxIns, benzene, bIs(ChloRomethyl)etheR And ChloRomethyl methyl etheR, 1,3-butAdIene, 2,3,7,8-tetRAChloRodIbenzo-pARA-dIoxIn, 2,3,4,7,8-pentAChloRodIbenzofuRAn, And 3,3’,4,4’,5-pentAChloRobIphenyl, ethylene oxIde, foRmAldehyde, sulfuR mustARd, VInyl ChloRIde, IsopRopyl AlCohol mAnufACtuRe by the stRong-ACId pRoCess, mIsts fRom stRong InoRgAnIC ACIds, oCCupAtIonAl exposuRes duRIng IRon And steel foundIng, oCCupAtIonAl exposuRe As A pAInteR, oCCupAtIonAl exposuRes In the RubbeR mAnufACtuRIng IndustRy. beCAuse the sCope of Volume 100 Is so bRoAd, Its monogRAphs ARe foCused on key InfoRmAtIon. eACh monogRAph pResents A desCRIptIon of A CARCInogenIC Agent And how people ARe exposed, CRItICAl oVeRVIews of the epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys, And A ConCIse ReVIew of the Agent’s toxICokInetICs, plAusIble meChAnIsms of CARCInogenesIs, And potentIAlly susCeptIble populAtIons, And lIfe-stAges. detAIls of the desIgn And Results of IndIVIduAl epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys ARe summARIzed In tAbles. shoRt tAbles thAt hIghlIght key Results ARe pRInted In Volume 100, And moRe extensIVe tAbles thAt InClude All studIes AppeAR on the monogRAphs pRogRAmme websIte (http://monogRAphs.IARC.fR). It Is hoped thAt thIs Volume, by CompIlIng the knowledge ACCumulAted thRough seVeRAl deCAdes of CAnCeR ReseARCh, wIll stImulAte CAnCeR pReVentIon ACtIVItIes woRldwIde, And wIll be A VAlued ResouRCe foR futuRe ReseARCh to IdentIfy otheR Agents suspeCted of CAusIng CAnCeR In humAns. D es ig n by A ude la d es m ot s
378 citations
Cites background from "Alert for an epidemic of oral cance..."
...Almost all smokeless tobacco products contain additives, such as ammonia, carbonate or bicarbonate, to raise the pH (Nair et al., 2004)....
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TL;DR: The aim of this review is to provide an update on epidemiology of OC between 2000 and 2012 and to have cancer surveillance at the national-level to collect and utilise data for cancer prevention and control programs.
Abstract: The prevalence of oral cancers (OC) is high in Asian countries, especially in South and Southeast Asia. Asian distinct cultural practices such as betel-quid chewing, and varying patterns of tobacco and alcohol use are important risk factors that predispose to cancer of the oral cavity. The aim of this review is to provide an update on epidemiology of OC between 2000 and 2012. A literature search for this review was conducted on Medline for articles on OC from Asian countries. Some of the articles were also hand searched using Google. High incidence rates were reported from developing nations like India, Pakistan, Bangladesh, Taiwan and Sri Lanka. While an increasing trend has been observed in Pakistan, Taiwan and Thailand, a decreasing trend is seen in Philippines and Sri Lanka. The mean age of occurrence of cancer in different parts of oral cavity is usually between 51-55 years in most countries. The tongue is the leading site among oral cancers in India. The next most common sites in Asian countries include the buccal mucosa and gingiva. The 5 year survival rate has been low for OC, despite improvements in diagnosis and treatment. Tobacco chewing, smoking and alcohol are the main reasons for the increasing incidence rates. Low socioeconomic status and diet low in nutritional value lacking vegetables and fruits contribute towards the risk. In addition, viral infections, such as HPV and poor oral hygiene, are other important risk factors. Hence, it is important to control OC by screening for early diagnosis and controlling tobacco and alcohol use. It is also necessary to have cancer surveillance at the national-level to collect and utilise data for cancer prevention and control programs.
362 citations
TL;DR: Following Adler's theory and the principles of the "Ottawa Charter for Health Promotion", conditions such as education, sustainable resources, social justice, and equity must be satisfied before the implementation of physical health promotion campaigns.
345 citations
Cites background from "Alert for an epidemic of oral cance..."
...Reactive oxygen species generation in the oral cavity due to auto-oxidation of polyphenols contained in areca nut and enhanced by the alkaline pH from slaked lime has been reported.(52,53) In areas at very high prevalence of betel quid chewing without tobacco, 50% of cases among men and almost 90% among women are attributable to this behaviour....
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TL;DR: Global 'oral cancer' is the eighth most common cause of cancer-related deaths, although many people are unaware of its existence, and more than 90% are squamous cell carcinomas arising in the mucous membranes of the mouth and oro-pharynx.
Abstract: People diagnosed with malignant neoplasms often feel afraid and alone. However, cancer is largely an avoidable disease, and studies have shown that more than two-thirds of cancer deaths may be prevented through lifestyle modification, early detection and effective treatment. The World Health Organization (WHO) estimates that nearly 12.7 million new cases and 7.6 million cancer deaths occurred worldwide in 2008 (27). Oral cancers are malignant neoplasms that affect the structures or tissues of the mouth. They may be a primary lesion that originated in the mouth, a metastasis from a distant site, or an extension from an adjoining site. In quoting detailed epidemiological data, it is necessary to distinguish between these origins, and to ascertain which structures are included, e.g. the vermillion borders of the lips are sometimes included and sometimes not. Globally, 'oral cancer' is the eighth most common cause of cancer-related deaths, although many people are unaware of its existence (92). Of these oral cancers, more than 90% are squamous cell carcinomas arising in the mucous membranes of the mouth and oro-pharynx.
295 citations
Cites background from "Alert for an epidemic of oral cance..."
...Moreover, generation of reactive oxygen species, such as the hydroxyl radical (HO), in the oral cavity by auto-oxidation of polyphenols contained in areca nut (a process enhanced by the alkaline pH provided by the slaked lime) has been reported (51, 84)....
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References
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TL;DR: This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists, and it is concluded that hepatitis D virus cannot be classified as a human carcinogen.
Abstract: Viral hepatitis in all its forms is a major public health problem throughout the world, affecting several hundreds of millions of people. Viral hepatitis is a cause of considerable morbidity and mortality both from acute infection and chronic sequelae which include, in the case of hepatitis B, C and D, chronic active hepatitis and cirrhosis. Hepatocellular carcinoma, which is one of the 10 commonest cancers worldwide, is closely associated with hepatitis B and, at least in some regions of the world, with hepatitis C virus. This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists. (It is interesting to note in passing that some 5000 papers on viral hepatitis are published annually in the world literature.) The epidemiological, clinical and experimental data on the association between infection with hepatitis B virus and primary liver cancer in humans are reviewed in a readable and succinct format. The available information on hepatitis C and progression to chronic infection is also evaluated and it is concluded (perhaps a little prematurely) that hepatitis C virus is carcinogenic. However, it is concluded that hepatitis D virus, an unusual virus with a number of similarities to certain plant viral satellites and viroids, cannot be classified as a human carcinogen. There are some minor criticisms: there are few illustrations and some complex tabulations (for example, Table 6) and no subject index. A cumulative cross index to IARC Monographs is of little value and occupies nearly 30 pages. This small volume is a useful addition to the overwhelming literature on viral hepatitis, and the presentation is similar to the excellent World Health Organisation Technical Reports series on the subject published in the past. It is strongly recommended as a readable up-to-date summary of a complex subject; and at a cost of 65 Sw.fr (approximately £34) is excellent value. A J ZUCKERMAN
11,533 citations
01 Jan 2001
2,870 citations
TL;DR: The annual incidence rates and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world and tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.
Abstract: The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer—by far the most important cancer of women (19.1% of the total)—is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.
1,685 citations
TL;DR: What are the mechanisms by which this deadly combination of nicotine and carcinogens leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?
Abstract: The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?
1,272 citations