the incidence rates of oral cancer are 3.7% for men 
 and 2.6% for women in the sudan .
several lifestyle risk factors 
 for the development of oral cancer are familiar , including tobacco products , alcohol , 
 infections , dietary factors , chemical irritants and frank carcinogens .
prevalence 
 of oral cancer is 3.2% in sudan and the disease is mainly attributed to n - nitrosamine 
 rich oral snuff consumption .
there are mainly 4 smokeless tobacco products : loose 
 leaf or chewing tobacco , snuff , plug tobacco and twist or roll tobacco .
chewing 
 tobacco and snuff are by far the most widely distributed types of smokeless tobacco . 

however , snuff is now 
 habitually used orally by insertion it between lower gum and cheek or lip ( dipping ) 
 .
the oral use of snuff in north america and western 
 europe is causally associated with an increased risk for cancer of the oral cavity 
 and pharynx .
snuff dipping has also been incriminated as being associated with cancer 
 of the nasal cavity , oesophagus , pancreas , kidney and urinary bladder [ 2 - 6 ] , 
 and other pre - neoplastic changes such as leukoplakia
. however , all these risk factors are beyond the scope 
 of the present review .
the main goal of this paper was to review the studied risk 
 factors that linked to aetiology of oral cancer in sudan .
in this review 33 studies published up to august 
 2012 in the aetiology of oral cancer from sudan were included .
they were identified 
 through searches of the medline database , using the keywords : " sudan " , " toombak " , 
 " infection " , " hpv " , " oral hygiene " , " alcohol " , " hot meals " , " cancer " , " oral squamous 
 cell carcinoma " and " risk factors " .
papers were also searched among those quoted 
 as references in the retrieved studies , as well as , in a few previous reviews . only 
 papers in english were considered .
in the sudan , oral snuff , known locally as toombak , 
 is home - made from finely ground leaves of nicotiana rustica , a tobacco species with 
 a particularly high content of nicotine and minor alkaloids .
this tobacco is mixed 
 with natron or atron ( sodium bicarbonate ) ( about 4:1 ) , then water is added to the 
 mixture , and after a period of about 2 hours or longer the mixture , called " saffa " 
 .
atron , opposed to lime in other parts of the world , is probably added to toombak 
 for its alkaline effects .
it has been shown that at high ph ( 11.0 - 11.8 ) nicotine 
 is completely protonated and its rate of absorption is increased . 

n - nitrosamines : the study by idris et al .  
 have analyzed the tobacco specific nittrose amine ( tsna ) levels in toombak and found 
 unusually high levels of these tsnas compared to the reported levels in any snuff 
 .
these high levels of tsnas found 
 in toombak were partially attributed to the use of tobacco species , nicotiana rustica , 
 and fermentation of toombak at elevated temperature , prolonged storage , and contamination 
 during processing [ 13 - 15 ] .
therefore , assuming chronic toombak 
 use , the minimum daily dose of nnk to which these users were exposed was 0.12 - 
 0.44 mg .
epidemiological evidence suggests that toombak is 
 a risk factor for cancer of the oral cavity and possibly of the oesophagus in the 
 sudan [ 17 - 19 ] .
data from 1,916 cases of oral neoplasms occurring 
 in the sudan in a 16-year period , from january 1970 to december 1985 , were retrieved 
 and analyzed .
the study revealed a relatively high frequency of oral neoplasms in 
 comparison with neighbouring countries .
squamous - cell carcinoma was the most common 
 oral malignancy ( 66.5% ) , followed by tumours of the salivary gland ( 14.7% ) , neoplasms 
 of non - odontogenic and non - epithelial origin ( 9.6% ) and odontogenic neoplasms ( 8.6% ) . 

female toombak use 
 is considered social stigma in sudan , consequently the 95% of toombak users were 
 males , which supports its etiological effects . in sweden ,
snus ( locally known as snus ) , was introduced 
 since the year 1637 .
the study by idris et al . compared between snus ( sweden ) and 
 toombak .
snus and toombak dippers develop a clinically and histologically characteristic 
 lesion at the site of dipping .
snus was associated with a lower risk of cancer of 
 the oral cavity ( relative risk : rr 5 - 6-fold ) compared to high risk of toombak ( rr 
 7.3 - 73.0-fold ) . clinical ( n = 281 ) and histopathological ( n = 141 ) 
 characteristics of toombak - associated oral mucosal lesions detected in an epidemiological 
 study in northern sudan in 1992/93 found parakeratosis , pale surface staining of 
 the epithelium and basal cell hyperplasia were commonly observed , but epithelial 
 dysplasia was infrequent ( 10/141 ) .
ultra structural features 
 oral toombak dipper s lesions with distinctive sub epithelial hyaline deposits their 
 bulk is made up of collagen , as typical cross - striated fibrils . the pathogenesis 
 of this deposit could therefore be interpreted as over - production and/or reduced 
 turnover of collagen by resident fibroblasts , which is further altered by the ingredients 
 of toombak . in a study investigated the effects of toombak on 
 primary normal human oral keratinocytes , fibroblasts , and a dysplastic oral keratinocytic 
 cell line , compare to swedish snuff , a potential for toombak , higher than for swedish 
 snuff , to damage human oral epithelium .
furthermore , in 
 oscc , apoptosis was associated with bax expression and was unaffected by p53 gene 
 status or toombak use in oscc from the sudan .
the study by ibrahim et al .  
 analyzed 14 oral squamous - cell carcinomas ( osccs ) and 8 pre - malignant oral lesions 
 from different sudanese patients for prevalence of mutations in exons 5 to 9 of 
 the p53 gene in relation to toombak - dipping status .
osccs ( 14 from sudan , 28 from 
 scandinavia ) , and 3 pre - malignant oral lesions from sudanese non - dippers were used 
 as controls .
a statistically significant ( p < 0.05 ) increased incidence in mutations 
 of the p53 gene was found in osccs from toombak dippers ( 93% ; 13/14 ) , as compared 
 with those from non - dippers in sudan ( 57% ; 8/14 ) and in scandinavia ( 61% ; 17/28 ) 
 respectively .
several studies from sudan have proved that toombak 
 use is a major risk factor that responsible of high frequencies of potential malignant 
 oral lesions and oral cancers and in particular osccs in the sudan .
most of tumours 
 were observed at the site of dip application ( lower lip ) .
oral cancer seems to be 
 gender - specific , as the majority of cases were males [ 26 - 31 ] .
however , all of the preceded discussed literatures 
 support the criminal role of toombak in the aetiology of oral cancer in the sudan . 

probably toombak has a major role but it is not alone responsible of oral cancer 
 in the sudan , particularly in the recent years with dramatic increase in overall 
 cancer risk .
most oral cancer cases and deaths are due to both 
 individual predisposition , linked to specific genetic characteristics , and exposure 
 to carcinogens , caused by lifestyle behaviours , particularly tobacco .
nicotine is only a minor component of tobacco leaves 
 and constitutes about 5% of the total weight of dry plant leaves .
when tobacco smoke is inhaled , 25% 
 of the nicotine reaches the brain in about seven seconds .
nicotine functions by 
 binding to nicotinic acetylcholine receptors , causing increased heart rate , vasoconstriction , 
 and alertness .
nicotine induces dependence among genetically , 
 mentally and socially predisposed individuals with addictive personalities .
tobacco carcinogenicity is more than evident and 
 about one fourth of oral cancer cases are attributable to cigarette smoking . 

specifically , tobacco products are causally linked to a variety of cancers , including 
 those of the lung , oral cavity , nasal cavity , larynx , oropharynx , hypopharynx , oesophagus , 
 stomach , liver , pancreas , bladder , ureter , kidney , cervix , and myeloid leukaemia
. more than 60 carcinogens are present in cigarette 
 smoke and at least 16 in unburned tobacco have been identified . the most important 
 are tobacco - specific nitrosamines , such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 
 ( nnk ) and n - nitrosonornicotine ( nnn ) , polycyclic aromatic hydrocarbons
in particular , nnk , nnn and pah have been causally 
 linked to oral cancer .
few women admit to tobacco use due to cultural norms 
 in the society , and among males the estimated prevalence is around 20% . 
 in most samples from indoor air polluted with environmental tobacco smoke ( ets ) , 

the highest concentration of an individual tsna is that of nnk . when nonsmokers 
 had remained for up to 2 hours in a test laboratory with high ets pollution , they 
 excreted measurable amounts of nnk metabolites in the urine , indicative of the uptake 
 of tsna .
a house to house cross - sectional survey of a random 
 population sample of 4,535 households was performed , as the first survey on tobacco 
 in the sudan .
of the 23,367 household members identified , 21,648 ( 92.6% ) eligible 
 individuals were questioned about tobacco use .
results showed that , among children 
 and adolescents ( 4 - 17 years ) prevalence of tobacco use was quite low ( 2% , range 
 1 - 2% ) , but there was an abrupt increase up to 25% in late adolescence . among the 
 adult population aged
18 years and older the prevalences of toombak use ( 34% ) and 
 cigarette smoking ( 12% ) among males were significantly higher than among females 
 ( 2.5 and 0.9% , respectively ) .
as part of the development of a screening procedure 
 for oral cancer and precancer , exfoliative cytology ( efc ) was applied to a retrospective 
 cohort to assess the presence and severity of oral epithelial atypia ( et ) in 300 
 subjects ( 100 toombak dippers ; 100 cigarette smokers ; 100 non - tobacco users ) without 
 prior knowledge of the subjects tobacco exposure .
et was ascertained in 29 subjects 
 and could not be ascertained in the remaining 271 . among the 29 subjects with et , 
 there were 11 ( 38% ) toombak dippers , 14 ( 48% ) cigarette smokers and 4 ( 14% ) non - tobacco 
 users .
among the 271 subjects without et , there were 89 ( 33% ) toombak dippers , 86 
 ( 32% ) cigarette smokers and 96 ( 35% ) non - tobacco users .
for the et among toombak 
 dippers and cigarette smokers , adjusted or and the 95% ci were found to be 3 ( 0.91 
 - 9.7 ) and 4 ( 1.2 - 12.3 ) , respectively .
both in tobacco smoke and smokeless tobacco , carcinogenic 
 n - nitroso compounds ( noc ) are implicated as dna - damaging agents in cancers of the 
 aerodigestive tract and the pancreas .
poor oral hygiene was found to contribute 
 to the formation of nitrosamines in the oral cavity .
the evidence so far accumulated 
 demonstrates that tobacco habits increase endogenous noc formation , thus adding 
 to the burden of exposure by preformed carcinogenic noc in tobacco products . however , in view of these studies , smoked tobacco 
 has a role in aetiology of oral cancer , but how far this is contributing in oral 
 cancer in sudan and how far it is significant is unknown , since there is lack of 
 data in this context .
alcoholic beverages are a heterogeneous group of 
 beverages , with variable number , type and concentration of components .
carbon dioxide , minerals ( mostly potassium , phosphates 
 and sodium ) , amino - acids , organic and inorganic acids , polyphenols and carbohydrates 
 are prevailing in beers .
alcohols , carbohydrates ( mainly sugar and pectin ) , organic 
 acids , minerals ( mostly potassium , iron , phosphates and calcium ) , polyphenols , vitamins 
 and carbon dioxide are the major wine components , while spirit and liqueur composition 
 is very assorted , with common components being alcohols , acids ( mainly fatty and 
 acetic acid ) , esters , aldehydes , terpenes , ethereal oils and volatile bases .
indeed , among 
 individuals consuming 4 - 5 drinks daily , the risk for cancer of the oral cavity 
 is 2 - 3 folds higher than among non - drinkers [ 44 - 47 ] .
overall , 7 - 19% oral cancer cases are attributable 
 to heavy alcohol drinking .
. 
 the major alcohol metabolising enzymes are alcohol dehydrogenase , that oxidises 
 ethanol to acetaldehyde , and aldehyde dehydrogenase , that detoxifies acetaldehyde 
 to acetate .
acetaldehyde is responsible for the oral carcinogenic effect of ethanol , 
 owing to its multiple mutagenic effects on dna .
in addition , 
 ethanol is not the only carcinogen present in alcoholic drinks , other minor components , 
 such as nitrosamines , acrylamide , oxidized polyphenols are classified as probable 
 carcinogenic to humans , with animal experiments showing mutagenic activity on oral 
 epithelial cells . since alcohol consumption is considered illegal in 
 sudan , no available data about the relationship between alcoholic beverage consumption 
 and oral cancerous development .
the study evaluated cytological atypical changes in apparently 
 healthy oral mucosa exposed to smoking , alcohol , hot meals , and peppers .
the features 
 of cytological atypia were verified among 10 individuals , including 5 smokers , 2 
 alcohol users , 2 hot meals and peppers consumers , and one non - exposed . for atypia 
 among tobacco smokers ,
the adjusted odds ratio ( or ) and the 95% ci were found to 
 be 2 ( 0.246 - 16.24 ) .
increased keratinisation was detected among 27 ( 45% ) of the 
 smokers ( p < 0.0001 ) , 17 ( 32.7% ) of the pepper and hot meals consumers ( p < 0.005 ) , 
 4 ( 11.8% ) of the alcohol consumers , and among 2 ( 3.7% ) of the non - exposed group . 

statistical analyses revealed a greater mean number of agnors per nucleus in smokers 
 ( 3.68 ) followed by ( 2.82 ) alcohol consumers , compared to the habitual peppers and 
 hot meal consumers ( 2.28 ) and the non - exposed group ( 2.00 ) . 
 
however , no available data about alcoholic consumers 
 in the sudan , approximately 95% of the habitual use to drink in hide , since it is 
 considered as illegal and social stigma . consequently , nobody can estimated or even 
 imagine its burden as a risk contributes to the aetiology of oral cancer in the 
 sudan .
human papilloma viruses ( hpv ) infection the hpv are a large family of non - enveloped dna viruses , 
 mainly associated with cervical cancers .
recent epidemiologic evidence has suggested 
 that hpv may be an independent risk factor for oropharyngeal cancers . 

hpv has a wide disease spectrum affecting the cutaneous and mucosal areas of the 
 body , ranging from benign common warts to invasive carcinoma .
hpv infections have 
 been reported in a number of body sites , including the anogenital tract , urethra , 
 skin , larynx , tracheobronchial mucosa , nasal cavity , paranasal sinus , and oral cavity 
 .
hpv is one of the most prevalent infections in the world 
 with several new cases diagnosed every year .
there are more than 120 genetically different , 
 yet closely related hpvs that are referred to as genotypes . by definition ,
each 
 type is defined by having less than 90% dna base pair homology with any other identified 
 hpv type .
the hpv genome encodes dna sequences for six early 
 ( e1 , e2 , e4 , e5 , e6 , and e7 ) proteins associated with viral gene regulation and 
 cell transformation , two late ( l1 and l2 ) proteins which form the shell of the virus , 
 and one region of regulatory dna sequences .
the different hpv types are characterized 
 by genotypic variations in the dna base - sequences of e6 and e7 .
it is these genotypic 
 differences that permit stratification of the virus oncogenic phenotype into high , 
 intermediate- , and low - risk types . in the case of high - risk hpv infection and under 
 favourable conditions ,
the viral genome is integrated into the host genome , which 
 is the necessary event for the keratinocytes immortality . during this process of 
 integration , the circular form of viral genome breaks at the level of the e1 and 
 e2 regions , never at the level of the e6 or e7 region .
different studies have shown 
 that the integrated part of the genome corresponds to e1 , e6 , and e7 , while the 
 regions from e2 to e5 are lost and are not transcribed in the tumours .
the loss 
 of e2 during this process of integration produces the loss of e6 and e7 control . 

therefore , the sequences e6 and e7 are directly involved in the cellular cycle by 
 inhibiting the normal functions of p53 and prb , respectively .
the protein p53 is 
 known as the " genome s guard " and in the case of dna damage , the p53 can provoke 
 the arrest of cellular division and assure the time necessary for dna repair . if 
 damage can not be repaired , p53 is able to induce the programmed cellular death and 
 prevent the propagation of dna damage in subsequent generations of cells . in the 
 case of other types of tumours ,
p53 is usually mutated and acts as a real oncogene . 
 in the case of hpv infection
, e6 suppresses the properties of p53 gene product , 
 achieving the functional equivalent of the two hits required to knock out both alleles 
 of a tumour suppressor gene .
the e7 
 protein interacts with retinoblastoma protein ( prb ) , which is the crucial factor 
 for the cellular cycle control .
this interaction causes the release of the transcription 
 factor e2f , which is now free to act and can stimulate the cellular division .
e7 
 is also able to bind and inactivate the protein kinase inhibitors p21 and p27 and 
 can interact with different proteins whose significance has still not been determined 
 . hpv has gained much interest recently , 
 because it is accepted as important correlates of cervical cancer .
oral hpv infections 
 have not been studied to the degree as those of the genital tract , although the 
 evidence of association between certain tumours and hpv infection today is indisputable . 

oncogenic hpvs are associated with oral malignancies , but its prevalence varies 
 widely in different studies .
although study results are mixed , it seems possible 
 that smoking and alcohol use may interact with hpv infection to increase a person s 
 risk of oral cancer .
so , oral hpv infections need to be studied and investigated 
 deeply so that it can guide us for future cancer prevention programs , including 
 oral hpv vaccination for oral hpv infections .
nevertheless , few studies have investigated the role 
 of viruses in general and hpv in particularly in the aetiology of oral cancer in 
 the sudan .
the first study investigated potentially malignant oral mucosal lesions 
 from sudanese patients ( 9 hyperplasias/40 dysplasias ) .
hpv was found in only 2 sudanese 
 cases , both of which harboured both type 6 and type 11 : both these cases demonstrated 
 mild epithelial dysplasia .
another study from sudan investigated 
 a total of 40 cases ( patients with osccs ) and 15 controls ( patients with benign 
 lesions ) were included in the study .
the cases included ; carcinomas of the oral 
 cavity proper , carcinomas of the lip vermilion .
hpv was detected among 6 ( 15% ) of 
 the cases , four were hpv type 16 and two were hpv type 18 . 

a recent study from sudan reported the presence of hpv in head and neck cancers 
 ( hncs ) in general and in oral in particular .
hpv16 was the most prevalent type , with single infections present in 3/6 ( 50% ) cases , 
 whereas hpv18 and hpv33 were detected in 2/6 ( 33% ) and 1/6 ( 17% ) , respectively . 

hpv infections were detected in 3 ( 50% ) cases of oral cavity and 3 ( 50% ) cases of 
 pharynx .
furthermore , very limited studies have investigated 
 the role of other viruses such as , epstein - barr virus ( ebv ) and herpes simplex virus 
 ( hsv ) in the aetiology of oral cancer in sudan beside hpv .
using pcr / dna sequencing , 
 a study has investigated the prevalence of hpv , hsv and ebv dna in brush biopsies 
 obtained from 150 sudanese toombak dippers and 25 non - toombak dippers in formalin - fixed 
 paraffin - embedded tissue samples obtained from 31 patients with oral dysplasias 
 ( 25 toombak users and 6 non - users ) , and from 217 patients with oral cancers ( 145 
 toombak users and 72 non - users ) . in the brush tissue samples from toombak users
, 
 hpv was detected in 60 ( 40% ) , hsv in 44 ( 29% ) and ebv in 97 ( 65% ) of the samples . 

the corresponding figures for the 25 samples from non - users were 17 ( 68% ) positive 
 for hpv , 6 ( 24% ) positive for hsv and 21 ( 84% ) for ebv .
the formalin - fixed samples 
 with oral dysplasias were all negative for hpv . in the 145 oral cancer samples from 
 toombak users ,
hpv was detected in 39 ( 27% ) , hsv in 15 ( 10% ) and ebv in 53 ( 37% ) 
 of the samples .
the corresponding figures for the samples from non - users were 15 
 ( 21% ) positive for hpv , 5 ( 7% ) for hsv and 16 ( 22% ) for ebv .
these findings illustrate 
 that prevalence of hsv , hpv and ebv infections are common and may influence oral 
 health and cancer development .
these observations warrant further studies involving 
 toombak - associated oral lesions , to uncover the possible mechanisms of these viral 
 infections in the development of oral cancer , and the influence of toombak on these 
 viruses . in another study
investigated the prevalence of 
 hpv , hsv and ebv in 155 osccs from eight different countries from different ethnic 
 groups , continents and with different socioeconomic backgrounds , the highest prevalence 
 of hpv was seen in sudan ( 65% ) .
genetic factors have enhancing roles in many cancers 
 including oral cancer . limited studies have dealt with the investigation of association 
 between genetic factors and level of risk for development of oral cancer in sudan . 
 in a study aiming to explore possible range of gene expression profiles in head 
 and neck squamous cell carcinomas ( hnscc ) and pair wised normal controls from sudanese 
 ( n = 72 ) and norwegian ( n = 45 ) patients using a 15k cdna microarray and to correlate 
 the findings with clinicopathologic variables .
analysis of the two population 
 groups revealed a common set of 73 genes within three main biological pathways . 

this indicates that the development of hnsccs is mediated by similar biological 
 pathways regardless of differences related to race , ethnicity , lifestyle , and/or 
 exposure to environmental carcinogens .
of particular interest , however , was the 
 valuable association of gene expression signature found with toombak use and anatomic 
 site of the tumours .
the prevalence of mutations in exons 2 and 3 of the 
 s100a4 gene was analyzed in the 14 osccs from toombak - dippers and in 25 cases of 
 osccs from the control non - snuff - dippers .
of the 14 osccs investigated from toombak - dippers , 
 mutations in the p21waf1 exon 2 were found in 43% ( 6 out of 14 ) , compared to 14% 
 ( 2 out of 14 ) , 22% ( 6 out of 27 ) and 14% ( 5 out of 35 ) found in those from non - snuff - dippers 
 from the sudan , scandinavia and the usa / uk , respectively . 

the study by lazarus et al .   suggested that toombak components 
 such as tsnas may induce p53 mutations in head and neck sccs and are likely contributors 
 to the tobacco - induced carcinogenic load in humans .
a recent study investigated the prevalence of p53 
 codon 72 polymorphism in brush biopsies obtained from a sudanese population . a total 
 of 174 individuals
were included in the study ; chronic toombak users ( n = 152 ) and 
 non - users ( n = 22 ) .
dna was extracted from all the samples and genotyped for the 
 codon 72 polymorphism by polymerase chain reaction / restriction fragment length polymorphism . 

the arg / pro genotype was found in 53% of the 174 study participants , compared to 
 21% found with arg / arg and 26% found with pro / pro .
stratifying by toombak use , 28 
 ( 18% ) , 45 ( 29% ) and 79 ( 52% ) of the 152 samples from toombak users had arg / arg , 
 pro / pro and arg / pro respectively , compared to 9 ( 41% ) , 0 ( 0% ) and 13 ( 59% ) found 
 in the 22 samples from non users .
the differences between the samples from toombak 
 users and non users in arg / arg and pro / pro codon 72 polymorphism and hpv infection 
 were statistically significant ( p < 0.05 ) .
the study indicated that a high prevalence 
 of the genotype arg / pro at the p53 codon 72 may contribute to susceptibility to 
 oscc , especially in combination with the use of carcinogenic tobacco - specific nitrosamine 
 ( tsna)-rich toombak . in another study , 9 genes related to 
 apoptosis
, cell cycle regulation and intermediate filament proteins were selected 
 and their differential expression status was examined by real - time quantitative 
 rt - pcr in 26 samples of sudanese osccs and their matched normal controls .
the mrna levels of bcl2 , keratin 
 1 , keratin 13 and p53 were significantly lower and the level of survivin was significantly 
 higher in the oscc samples of the toombak users compared to their paired control 
 samples .
a significant down - regulation in keratin 1 and keratin 13 expression levels 
 was found in the oscc samples of the non - toombak users compared to their normal 
 control samples .
the differential expression of genes related to apoptosis , cell 
 cycle regulation and types i and ii keratin could be useful diagnostic markers and 
 provide valuable information for the understanding of oral malignancy in relation 
 to toombak use . besides tobacco and alcohol , other risk factors
have 
 been studied in relation to oral cancer in sudan . among these factors , diet and 
 nutrition
so far there is a lack of studies focusing on the prevalence of a wide spectrum 
 of oral mucosal lesions ( oml ) in patients with dermatologic diseases .
this is noteworthy 
 as skin lesions are strongly associated with oral lesions and could easily be neglected 
 by dentists .
a study from sudan found that oml were frequently diagnosed in skin 
 diseased patients and varied systematically with age , gender , systemic condition 
 and use of toombak .
epidemiological studies conducted in various populations 
 reported an inverse association between intake of fruit and vegetables and the risk 
 of cancer of the oral cavity .
thus , fruit and vegetables 
 appear to be the most consistent favourable dietary aspect on oral and pharyngeal 
 neoplasm . in a network of studies from italy , about 20 - 25% of cancers of the oral 
 cavity and pharynx
were attributed to low fruit and vegetable consumption , and the 
 population attributable risk , rose to 85 - 95% when tobacco and alcohol consumption 
 were also considered .
the evidence on the role of milk and dairy products , 
 as well as coffee and tea , on the risk of cancer of the oral cavity and pharynx 
 is scanty , and does not indicate any consistent association . 

, none of these factors has been investigated in the sudan . as sudan is very 
 large country with different climates
toombak plays a major role in the aetiology of oral 
 cancer in sudan , since it is a potent carcinogenic , as well as it acts as a synergistic 
 factor enhances the carcinogenesis of other etiological factors , such as genetic 
 factors and viruses .
the role of human papilloma virus in aetiology of oral cancer 
 is reasonable , but the question how far is it without toombak ?
the real contribution 
 of other risk factors such as viruses other than human papilloma virus , smoked tobacco 
 and alcohol still need more investigation other factors that have increased risk 
 or reverse risk need more investigation .
 abstractobjectivesto review the studied risk factors that 
 linked to aetiology of oral cancer in the sudan . 
 there have been numerous reports 
 in the increase in the incidence of oral cancer from various parts of the world . 
 a recent trend for a rising incidence of oral cancer , with the absence of the well 
 established risk factors , 
 has raised concern . 
 although , there are inconsistent data 
 on incidence and demographical factors , studies suggest that the physiologic response 
 to risk factors by men and women vary in different populations.material and methodsthis review principally examines 
 33 publications devoted to aetiology of oral cancer in the sudan , in addition to 
 some risk factors that are commonly practiced in the sudan.resultsseveral studies examining risk factors for 
 oral cancer include tobacco use ( smoked and smokeless ) , alcohol consumption , occupational 
 risk , familial risk , immune deficits , virus infection and genetic factors.conclusionstoombak use and infection with high 
 risk human papilloma virus ( hpv ) were extensively investigated and linked to the 
 aetiology of oral cancer in sudan . 
INTRODUCTION
MATERIAL AND METHODS
RESULTS
CONCLUSIONS
ACKNOWLEDGMENTS AND DISCLOSURE STATEMENTS