document: the association of this habit with oral cancer was noted over a century ago ; yet the chewing of betel quid in india was considered to be a comparatively innocuous practice with complete socio - cultural acceptance . in recent years it has emerged as a significant public health problem in india 
   . the normal cultural practice of betel nut ended up to a health hazard when tobacco was introduced by the european settlers four centuries ago . 
   in addition to its use for smoking , as the europeans demonstrated , tobacco somehow got mixed with betel quid and prepared to be chewed . in india 
   tobacco was culturally accepted as it was used with a culturally accepted betel quid substance . during the second half of the 20 th century , 
   the causal association between chewing of betel quid with tobacco and oral cancer was well established , so it could no longer be regarded as a completely innocuous practice . 
   the major culprit was clearly tobacco in the quid ; however , probably because of its ' exotic ' appeal , areca nut was erroneously thought of as playing a more important role . 
   betel nut was reported safe in many studies where only tobacco in the quid was held responsible for oral cancers . 
   later it was clear that betel nut chewing was responsible for oral submucous fibrosis ( osmf ) , an established precancerous condition with trismus . 
   osmf was a rare disease in the early 80 s , occurring generally among older age groups who chew betel quid frequently . 
   a later incidence of osmf increased amongst the indian young population as a result of increasing gutkha chewing . 
   the frequency of oral cancer has increased among young adults as a result of increasing in number of osmf ( a precancerous condition ) . 
   the increasing incidence of osmf and oral cancers during the last two decades was due to industrial manufacturing and marketing of these chewable mixtures gutkha . 
   the incidence of oral cancer is 12.5/100,000 and the largest numbers of oral cancer patients are present in india . in india , 
   this epidemic proportion of oral cancer in india is due to the rampant use of betel nut , betel quid , and gutkha and pan masala chewing which are proven to be carcinogens . 
   oral cancer is uncommon disease in the west but continue to be the major cause of cancer related death in indian men . 
   over last few decades , large funds have been spent to educate public , implement laws effectively , rehabilitate tobacco growers , build cessation facility , create health care infrastructure , etc to reduce the betel nut , betel quid , gutkha and other forms of chewable tobacco usage . 
   this is a retrospective study of 63 cases of oral cancer patients who were managed in kvg medical college sullia . 
   sixty three patients , 38 males and 25 females , were included in our study . 
   the youngest patient was 47 years old and the oldest was 73 . a detailed history of the patients was taken plus oral and oropharyngeal examination . 
   chest x - ray along with ap neck x - ray , lateral view and panoramic view were taken ( figure 1 ) . 
   the biopsy of the ulceroproliferative mass was taken ; histopathology of all specimens showed squamous cell carcinoma . 
   tnm staging ( tumor size , lymph nodes , metastasis ) showed most of the cases were in advanced stages . 
   all of 63 patients were managed according to the oral cancer management protocol and all signed written informed consent . 
   the mean age in males was 61.20 years and female median age was 59.92 years . 
   the mean duration of betel chewing in males was 18.56 years and in females was 20 years ( figure 2 ) . 
   all patients in our study changed to chewing packaged panmasala and gutkha which were easily available . 
   the mean duration of panmasala and gutkha chewing in males was 8.66 years and in females was 7.36 years ( figure 3 ) . 
   thirteen males ( mean 11.2 years ) in our study were tobacco smokers and 12 males ( mean 9.4 years ) were occasional alcohol drinkers . 
   twelve males ( mean 10.3 years ) and 14 females ( mean 8.4 years ) were workers in tobacco processing industry . 
   ischemic heart disease and hypertension were seen in 22 patients ( 16 males and 6 females ) . 
   oral submucous fibrosis and leukoplakia were excluded from the study after histopathological examination ( figure 4 ) . out of 63 cases , 14 had lip carcinoma , 41 with carcinoma of the buccal mucosa and 7 had carcinoma of tongue and there was 1 case of carcinoma of upper alveolus . 
   out of 14 cases of carcinoma of lip , 2 cases were in stage1 , 3 cases in stage 2 , 7 cases in stage 3 , and 2 cases in stage 4 . 
   out of 41 cases of buccal mucosa carcinoma , 4 were in stage 1 , 11 in stage 2 , 18 in stage 3 , and 8 cases in stage 4 ( figure 5 ) . 
   out of 7 cases of tongue carcinoma , 2 were in stage 1 , no cases in stage 2 , 2 cases in stage 3 , and 3 cases in stage 4 ( figure 6 ) . 
   the case of carcinoma of upper alveolus refused treatment and was lost in follow up ( figure 7 ) . 
   all stage 1 oral cancer patients in our study were treated by wide excision only and followed up for 6 months to 2 years . 
   three cases of lip carcinoma with stage 2 were treated by wide excision and postoperative radiotherapy ( figure 8) . 
   two cases of buccal mucosa carcinoma with stage 2 were widely excised and were sent for postoperative radiotherapy , 8 patients were sent for radiotherapy as they refused surgery and 1 refused radiotherapy ( table 1 ) . out of 7 cases of lip carcinoma with stage 3 , 3 patients refused treatment and 4 had wide excision with neck dissection and postoperative radiotherapy . 
   out of 18 cases of carcinoma of buccal mucosa stage 3 , 7 patients underwent wide excision with neck dissection plus radiotherapy , 11 refused surgery so they were referred to radiotherapy . 
   one case of carcinoma stage 3 had wide excision with radiotherapy and the other refused surgery but took radiotherapy . 
   two cases of lip carcinoma with stage 4 refused surgery so they were given radiotherapy . 
   all buccal mucosa carcinoma patients with stage 4 refused surgery but only 2 of them received radiotherapy . 
   a direct relation between oral cancer and duration of betel quid , gutkha and panmasala chewing was seen in our study . 
   betel nut may be consumed alone or as a betel quid in combination with betel leaf and slaked lime and may contain other substances like tobacco , catechu , spices or sweeteners [ 9 , 10 ] . 
   betel leaf that is commonly consumed with this nut contains a known carcinogen named safrole [ 9 , 10 ] . 
   the lime in the betel quid enhances the extraction of the betel nut alkaloids by salivary degradation and promotes carcinogenesis [ 9 , 10 ] . 
   the alkaloids in betel nut which are responsible for the biological actions in humans are arecoline , arecaidine , guvacine , and guvacoline [ 9 , 10 ] . asians and indians even after immigrating to western countries still continue the habit of betel nut chewing which show an addiction among these populations [ 9 , 10 ] . 
   the betel nut derived alkaloids are cholinergic agonists and they affect nervous system via acetylcholine . 
   prolonged use of betel nut causes peculiar facial and systemic features , staining of teeth , attrition of teeth , and creation of wear facets with higher incidence of periodontitis . 
   betel nut for consumption is obtained from areca catechu which is the fourth most common addictive substance after tobacco , alcohol , and caffeine . 
   it is possibly the second most consumed carcinogen after tobacco in the indian subcontinent . in india 
   , betel nut is chewed for variety of reasons such as stress reliever , mouth freshener , improving concentration , and for digestion after food . 
   addiction withdrawal symptoms are mood swings , anxiety , and irritability , loss of concentration , sleep disturbance and craving which were seen in most cases in our study . 
   betel nut psychosis has been reported in heavy users following sudden cessation of the habit . 
   india is the greatest producer of betel nut something like 330,000 million tonnes per year ( nearly half of global betel nut production ) . 
   the total area under betel nut cultivation in india is estimated to be around 372,000 hectares and total production is 340,000 tonnes . 
   it is estimated that nearly 10 million people depend on betel nut industry for their livelihood in india . 
   most of the betel nut production is consumed within india because it has limited export potential . 
   betel nut products ( gutkha , panmasala ) are being advertised as mouth fresheners which are misleading indian youth . 
   gutkha and panmasala are more dangerous than betel nut alone because they are kept in mouth for a longer time . 
   the other promoting factors in this industry are lack of statutory warning , low cost , easy availability , attractive packaging and aggressive marketing . 
   panmasala is basically a preparation of betel nut , catechu , cardamom , lime and a number of natural , artificial perfuming and flavoring materials . 
   gutkha is a variant of panmasala , in which in addition to these ingredients flavored chewing tobacco is added . 
   both products are often sweetened to enhance the taste .betel leaf is perishable and preparation of betel quid is somewhat complex or requires visits to shops selling pan / bq . with the emergence of commercial pan masala and gutkha about three decades ago , not only did the indian market witness massive growth in the sales of smokeless tobacco and betel nut products , but also a huge worldwide export market developed . 
   all our patients earlier chewed betel quid but turned to gutkha , pan masala chewing over the last two decades . just like tobacco , 
   the cancer causing properties of betel nut have been well - reported in animal , human and epidemiologic studies . 
   cancers caused by betel nut chewing also shows a strong dose - response relationship for frequency and duration of chewing . 
   n - nitroso compounds converted from betel nut alkaloids are responsible for oral and pharyngeal cancer . also betel nut chewing ( with or without tobacco ) 
   is associated with hepatocellular carcinoma , cholangiocarcinoma , cancers of the larynx , stomach , lung and cervix in humans . 
   betel nut is a synergistic carcinogen along with tobacco with which it is commonly consumed in india . 
   all patients in our study had betel quid and gutkha panmasala chewing as the etiology with smoking , alcohol consumption and working in tobacco processing factories as other etiologies . the who and international agency for research on cancer classified betel nut as a group 1 human carcinogens with sufficient evidence of increased risk of osmf ( precancerous oral lesion ) and cancers of the oral cavity , pharynx and esophagus [ 17 - 20 ] . 
   cancers caused by betel nut chewing also shows a strong dose - response relationship for frequency and duration of chewing . 
   it is postulated that betel nut - specific n - nitroso compounds converted from alkaloids are responsible for oral and pharyngeal cancer . 
   there are several other reports that have linked betel nut chewing ( with or without tobacco ) with hepatocellular carcinoma , cholangio - carcinoma , laryngeal cancers , stomach , lung and cervix in humans . 
   studies in mice have shown that , betel quid extract given by gavages produced carcinoma of lung , stomach , liver and salivary gland . 
   fibrosarcomas at the injection site were observed by subcutaneous injections of betelnut extracts in mice . 
   animal research has shown that panmasala in the diet led to tumors in various organs , most frequently adenocarcinoma of lung . in another experiment , 
   arecoline was given as gavage and it produced carcinoma of lung , stomach and hemangiomas of liver . 
   esophageal cancers increased 195 times , pharyngeal cancers 96.9 times and laryngeal cancers 40.3 times when betel quid chewers had habits of smoking and drinking . 
   betel quid chewing resulted in a statistically significant increase in the risk of overall mortality and cerebrovascular deaths in the elderly population [ 22 , 23 ] . 
   betelnut addiction has also been found to be associated with heart attacks , arrhythmia , metabolic syndrome and diabetes [ 24 - 27 ] . 
   chronic betel nut chewers women give birth to low weight babies similar to smoker women [ 29 , 30 ] . 
   betel nut and betel quid chewing has been a popular oral habit in india and many other southeast asian countries for a long time [ 31 , 16 ] . 
   betel nut , betel quid and gutkha chewing habit has become the top five oral habits ( including smoking , alcohol , tea , coffee , and betel chewing ) in the world . 
   there are about 200 - 600 million betel nut , betel quid and gutkha chewers in the world [ 28 , 29 ] . 
   they are proven carcinogens resulting in oral cancer , oral precancerous lesions , hepatocarcinoma , diabetes mellitus ( dm ) , cardiovascular diseases and other systemic diseases [ 31 , 16 ] . 
   india accounts for 1/3 of an estimated 3 million betel and tobacco related deaths in the world per year . in 2001 , the sale of cigarettes was banned to people under 18 . in view of high usages of betel nut , betel quid and other tobacco containing products such as gutkha and their proven role as a carcinogen , it is necessary to look into the hazardous effects of these addictions and their impact on health and society . 
   so a ban on betel nut , betel quid and tobacco in any form is immediately necessary to eradicate the menace of the morbidity . 
   panmasala and gutkha have flooded the indian market as cheap and convenient betel quid substitutes and become popular across all age groups wherever betel nut is abundantly used . 
   there is sufficient evidence that chewing of betel nut with or without tobacco and lime are carcinogenic in humans . 
   some restrictions on the manufacture and sale of these products are being implemented but because of seriousness of the situation , a permanent ban on gutkha and panmasala is necessary as they are well - established oral cancer causing agents . 
   an emphasis on health education aiming to reduce and later eliminating betel nut and tobacco products should be placed . 
   panmasala and gutkha have flooded the indian market as cheap and convenient betel quid substitutes and become popular across all age groups wherever betel nut is abundantly used . 
   there is sufficient evidence that chewing of betel nut with or without tobacco and lime are carcinogenic in humans . 
   some restrictions on the manufacture and sale of these products are being implemented but because of seriousness of the situation , a permanent ban on gutkha and panmasala is necessary as they are well - established oral cancer causing agents . 
   an emphasis on health education aiming to reduce and later eliminating betel nut and tobacco products should be placed .
summary: backgroundbetel nut and betel quid chewing are from major etiological factor for oral cancer . 
   they also increase the risk of systemic diseases such as asthma , diabetes mellitus , metabolic syndrome , myocardial infarction , hypertension , and other cardiovascular diseases . 
   methodssixty three patients of oral cancer in our institution during jan . 
   2007 to may 2011 were included in our study . 
   this study included 14 cases of lip carcinoma , 41 cases of buccal mucosa carcinoma , 7 cases of tongue carcinoma , and 1 case of carcinoma of upper alveolus . 
   duration of use of betel quid , pan masala , and gutkha were studied as well as management.resultsall patients in our study have been chewing betel - quid for 6 - 31 years ( mean19.42 years ) . 
   all of them quit betel quid and used easily available panmasala and gutkha for 4 - 13 years ( mean 8.28 years ) . 
   nine cases of lip carcinoma , 13 cases of buccal mucosa carcinoma and 3 cases of tongue carcinoma were treated with surgery . 
   seven cases of lip carcinoma , 30 cases of buccal mucosa carcinoma and 5 cases of tongue carcinoma were treated with post operative or palliative radiotherapy.conclusionbetel nut chewing with or without tobacco and lime are proven to be carcinogens in human . direct relationship between oral cancer and betel quid , gutkha , and panmasala use 
   has been shown in our study . as betel quid , panmasala and gutkha chewing 
   were proven to be carcinogens , a permanent ban on manufacturing and sale of these products should be implemented .