the indian populations in brazil and in other countries worldwide are not well studied , with rare published reports . the study of culturally distinct indigenous populations , as well as their contact with and influence of non - indigenous groups in relation to their behavior and merging of new habits as risk factors for prostate diseases is intriguing . many studies have been reporting for many years the huge ethnical difference of the incidence of prostate diseases , including prostate cancer ( pca ) as well as the concentration of prostatic specific antigen ( psa ) in different populations around the world ( 1 ) . it is discussed if these differences are derived from biological diversity of populations or from environmental factors that would modify their hereditary traits , mainly dietary habits and lifestyle ( 2 ) . age , black race and familial history of cancer are well stablished factors for high risk of prostate cancer ( 1 ) . most studies suggest that the ingestion of fatty food , cooked food , selenium , exposure to pesticides and fertilizers , physical activity and socio - economic status are factors that can contribute to observed differences in many countries , regions or eventually races ( 3 ) . variations of frequency of pca among caucasians , native alaskans and indians are well documented in the usa ( 4 , 5 ) . however , in the indigenous population of brazil , data regarding incidence , prevalence and risk factors for prostate disease are rare and only a few studies addressed clinical and anthropometric data in that population ( 6 - 8 ) . in view of scarce information about the profile of male health of indigenous populations of extreme north of brazil , we decided to analyze gstp1 and tp53 polymorphisms , psa and testosterone serum values and digital rectal exam , correlating the results with anthropometric characteristics , lifestyle , and especially dietary habits in order to elucidate the interaction of genetic background and environmental exposure in relation to prostatic diseases . from march , 2010 , to march , 2011 , a total of 315 healthy men with 40 or more years old were prospectively evaluated by the same examiner , after signing a written consent form . 228 indians were admitted to indian house of health in boa vista , roraima , brazil ( casai / rr ) , through a campaign , and 87 non - indigenous healthy men that donated blood were included in the control group . polymorphisms of codon 72 of tp53 and gstp1 were analyzed ; they are involved in the detoxification and repair of dna ( 9 ) ( figure-1 ) . the data were correlated to anthropometric values , lifestyle habits , serum psa and testosterone and digital rectal exam ( dr ) of the indigenous populations of northern brazil . prostatic symptoms were evaluated with the ipss ( international prostate symptom score ) questionnaire validated to portuguese ( 10 ) . genomic dna was extracted using the standard protocol of phenol - chlorophorm , adapted from the cancer genetic molecular laboratory of the university of campinas - unicamp , brazil . in order to verity the dna purity and quality of the extract , the samples were quantified using the uv - spectrophotometer picodrop limited ( cambridgeshire , uk ) . genotyping of the two proposed polymorphisms gstp1 codon 105 ( rs1695 ) and tp53 codon 72 ( rs1042522 ) was conducted using taqman snp genotyping ( 7500 real time pcr systems ) essay . in order to understand the impact of the introduction of new dietary habits , lifestyle and behaviors from the non - indigenous population , we identified and compared two different ethnic groups , with bigger and smaller distance from the urban centers , with consequent greater of smaller contact and merging of habits of non - indigenous people : respectively , macuxis and yanomamis . all local authorities were officially notified ( funasa and casai ) , and agreed with this research . categorical variables were compared using the exact fisher test of chi - square test , as appropriated . non - normally distributed numerical variables were compared using the mann - whitney test ( two groups ) or kruskal - wallis ( three of more groups ) . the analysis of allelic and genotypic frequencies was made using the laws of equilibrium of hardy - weinberb . categorical variables were compared using the exact fisher test of chi - square test , as appropriated . non - normally distributed numerical variables were compared using the mann - whitney test ( two groups ) or kruskal - wallis ( three of more groups ) . the analysis of allelic and genotypic frequencies was made using the laws of equilibrium of hardy - weinberb . no indian reported prostatic symptoms ; median age was 54.7 years , abdominal circumference was 86.6 cm and bmi was 23.9 kg / m2 ; 64.8% had normal bmi ( 18.5 to 25,0 kg / m ) , 29.5% overweight ( 25,0 to 30 kg / m ) , 3.5% obesity ( 30.0 kg / m ) and 2.2% low weight ( < 18.5 kg / m ) . median psa was 0.52 with values 2.5 ng / ml in 91.3% , > 2.5 ng / ml in 9 cases ( 8.7% ) , and 5.8% with psa 4 table 1clinical and laboratory characteristics of indians ( n=228).characteristicvalue or nage , years  interval40 to 91  meansd54.6912.06  median52.5bmi , kg / m 
 interval17.3 to 33.8  meansd23.943.11  meann23.9abdominal circumference , cm  interval62 to 110  meansd86.648.25  median86smoking  yes78 ( 34.2 )  no150 ( 65.8)alcohol abuse  yes95 ( 41.7 )  no133 ( 58.3)testosterone , ng / dl ( n=65 )  interval14 to 889  meansd4951.78  median472digital rectal exam , grams ( n=224 )  interval10 to 80  meansd21.568.74  median20psa , ng / ml ( n=103 )  interval0.02 to 13.95  meansd1.101.89  median0.52 
 
 table 2demographic characteristic of non - indians ( controls).characteristicn ( % ) age , years ( n=87 )  interval18 to 86meansd41.115.3median ( iqr)39 ( 30 - 51)ethnical group ( n=87 )  white66 ( 75.9%)non - white21 ( 24.1%)smoking ( n=45 )  yes9 ( 20.0%)no36 ( 80.0% ) 
 iqr= 
 interval interquartis ; 
 sd= 
 standard deviation 
 
 iqr= 
 interval interquartis ; 
 sd= 
 standard deviation 83 indians completed the question form ; mean age was 53 years . most informed absence of symptoms or light symptoms ( score 7 ) and only 15% moderate symptoms ( score 8 - 19 ) ; ipss varied from 3 to 19 , median 7 . cassava ( manioc ) ( 98.7% ) , fish ( 25.2% ) and animal hunt meat ( 86.4% ) were the most frequent food ingested during basic indian meals , followed by flour ( 41.7% ) , fruits ( 28.9% ) and vegetables ( 27.2% ) . meat , chicken and pork were referred only by 17.1% , 16.7% and 5.7% respectively . when the ethnic groups were compared , the yanomamis were younger with lower values of bmi and lower prostate volume at dr . there were no differences between testosterone and psa levels , and psa increased with age ( table-3 ) . table 3demographic and clinical characteristic of macuxis , yanomamis and  others ethnical groups.characteristicmacuxi n ( % ) yanomami n ( % ) other ethnical groupsp ( macuxi x yanomami)p ( macuxi x yanomami x other ethnical groups)age , yearsn=99n=33n=95  interval40 to 9140 to 7340 to 810.0020.0034meansd57.713.150.09.753.311.0median ( iqr)56 47 - 6548 42.5 - 55.752 44 - 60bmi , kg / mn=99n=33n=95  interval17.4 to 33.817.3 to 26.918.3 to 31.0<0.001<0.001meansd24.83.221.42.323.32.9prostatic volume ( dr ) ( g)n=99n=32n=93  interval10 to 4510 to 3010 to 80<0.0010.0014median ( iqr)20 15 - 3015 15 - 2020 15 - 25prostatic volume ( dr ) ( g)n=99n=32n=93  2052 ( 52.5)27 ( 84.4)57 ( 61.3 )  0.0058>2047 ( 47.5)5 ( 15.6)36 ( 38.7 )  total testosterone ( ng / dl)n=34n=8n=23  interval99 - 82666 - 55014 - 8890.2070.390meandp502.2177.7414.4155.6512.2185.0psa ( ng / ml)n=54n=11n=38  interval0.1 - 13.90.03 and 6.20.02 - 5.10.3490.3573median ( iqr)0.6 0.4 - 1.00.48 0.11 - 1.020.41 0.23 - 0.96psa ( ng / ml)n=54n=11n=38  2.549 ( 90.7)10 ( 90.9)35 ( 92.1 )  0.9734>2.55 ( 9.3)1 ( 9.1)3 ( 7.9 )  free psa ( ng / ml)n=54n=11n=38  < 0.5223 ( 42.6)6 ( 54.5)22 ( 57.9 )  0.33060.5231 ( 57.4)5 ( 45.4)16 ( 42.1 ) 
 n= 
 number of individuals with available data ; 
 dr= 
 digital rectal exam ; 
 iqr 
 = interval interquartis ; 
 psa= 
 prostatic specific antigen ; 
 sd 
 = standard deviation 
 
 n= 
 number of individuals with available data ; 
 dr= 
 digital rectal exam ; 
 iqr 
 = interval interquartis ; 
 psa= 
 prostatic specific antigen ; 
 sd 
 = standard deviation indian and non - indigenous showed super - representation of haplotype arg / arg , 74.5% versus 42.5% , p<0.0001 , polymorphism tp53 and ile / ile 35.3% versus 60.9% ; ile / val 45.9% versus 28.7% and val / val 18.8% versus 10.3% , for gstp1 , p=0.0003 , respectively ( table-4 ) . table 4frequency of variants tp53 and gstp1 in non - indians and indias.characteristicnon-indiansindiansp*tp53  arg / arg ( gg)37 ( 42.5%)152 ( 74.5% )  arg / pro ( gc)39 ( 44.8%)42 ( 20.6%)<0.0001  pro / pro ( cc)11 ( 12.6%)10 ( 4.9% )  gstp1  ile / ile ( a / a)53 ( 60.9%)73 ( 35.3% )  ile / val ( a / g)25 ( 28.7%)95 ( 45.9%)0.0003  val / val ( g / g)9 ( 10.3%)39 ( 18.8% ) 
 a= 
 adenin ; 
 arg= 
 arginin ; 
 c= 
 citosine ; 
 g= 
 guanine ; 
 ile= 
 isoleucin ; 
  pro= 
 proline ; 
 val= 
 valin.*chi - square 
 
 a= 
 adenin ; 
 arg= 
 arginin ; 
 c= 
 citosine ; 
 g= 
 guanine ; 
 ile= 
 isoleucin ; 
  pro= 
 proline ; 
 val= 
 valin . we observed an association of gstp1 genotype and serum psa , with predominance of polymorphic homozygous genotype val / val in individuals with lower psa levels ( p=0.0361 ) . tables 5 and 6 show demographic and clinical characteristics , according to variants of tp53 and gstp1 , respectively . table 5demographic and clinical characteristics according to p53 variant.factorsarg/arg n ( % ) arg / pro n ( % ) pro / pro n ( % ) pethnical groupn=151n=42n=10  macuxi70 ( 46.4)13 ( 30.9)2 ( 20 )  yanomami21 ( 13.9)7 ( 16.7)00.0637*other ethnical groups60 ( 39.7)22 ( 52.4)8 ( 80 )  smokingn=152n=42n=10  no55 ( 38.7)15 ( 35.7)4 ( 40.0)0.9674*yes97 ( 63.8)27 ( 64.3)6 ( 60.0)alcohol abusen=152n=42n=10  no65 ( 42.8)16 ( 38.1)7 ( 70)0.1840*yes87 ( 57.2)26 ( 61.9)3 ( 30)age , yearsn=152n=42n=10  interval40.0 a 91.040.0 a 81.040.0 a 78.0  median ( iiq)52.0 ( 44.0 - 63.0)54.5 ( 45.0 - 61.0)56.0 ( 47.0 - 68.0)0.7303 * * 
 iiq= 
 interval interquartil ; 
 arg= 
 arginin ; 
 pro= 
 prolin.*chi - square ; * * kruskal - wallis . table 6demographic and clinical characteristic , according to gstp1 variant.fatoresile/ile n ( % ) ile / val n ( % ) val / val n ( % ) pethnical groupn=73n=94n=39  macuxi29 ( 39.7)42 ( 44.7)16 ( 41.0)0.6513 *  yanomami12 ( 16.4)14 ( 14.9)3 ( 7.7 )  other ethnical groups32 ( 43.8)38 ( 40.4)20 ( 51.3 )  smokingn=73n=95n=39  no27 ( 37.0)33 ( 34.7)14 ( 35.9)0.9553 *  yes46 ( 63.0)62 ( 65.3)25 ( 64.1)alcohol 
  abusen=73n=95n=39  no37 ( 50.7)38 ( 40.0)15 ( 38.5)0.2997 *  yes36 ( 49.3)57 ( 60.0)24 ( 61.5 )  age , years  interval40.0 a 88.040.0 a 91.040.0 - 84.00.3975 * *  median ( iiq)50.0 ( 44.0 - 63.0)53.0 ( 45.0 - 62.0)55.0 ( 45.2 - 64.7 ) 
 iiq= 
 interval interquartil ; 
 ile= 
 isoleucin ; 
 val= 
 valin.*chi - square : * * kruskal - wallis 
 
 iiq= 
 interval interquartil ; 
 ile= 
 isoleucin ; 
 val= 
 valin . * chi - square : * * kruskal - wallis our data show that the indigenous population presents low prostate volume , bmi close to normality and healthy dietary habits , different from the brazilian population . also , indians present lower incidence of prostatic symptoms ( according to ipss , only 15% moderate ) in relation to non - indigenous brazilians with same age evaluated in a screening program of prostate cancer ( 29% , with 24% of moderate symptoms and 5% with severe symptoms ( 11 ) . among the ethnic groups , the yanomamis were younger , with lower values of bmi and prostatic volume , although with similar serum values of psa and testosterone . the analysis of polymorphism of tp53 codon 72 and gstp1 demonstrated significant differences between indians and non - indigenous and the homozigous polymorphic genotype val / val was related to significant lowers levels of serum psa . these differences may be related to age differences , but also due to behavior and dietary habits between the ethnic groups , although without clinical significant difference of age in regard to prostatic evaluation . the greater contact of the macuxi population with non - indigenous populations may have merged new behavior and dietary habits similar to non - indians . in contrast , the greater geographic distance from urban centers may have contributed to preservation of dietary habits and lifestyle of the yanomamis . in this group , all participants ate animal hunt meat and fish , none reported ingestion of bovine meat and only two reported chicken ingestion . also , genetic differences associated to racial and ethnical factors have influence on the predisposition to prostatic diseases . recently our group identified genetic polymorphisms related to the metabolism of carcinogens that can distinguish patients with high or low risk of pca or benign prostatic hyperplasia ( 12 ) . reference to this ethnical group , there were 10 cases per year ( median ) in the last 5 years . several studies have demonstrated that american indians present low risk for pca ( 13 - 15 ) . in one of the first studies that described the epidemiological profile of indians compared to white americans , dunham et al . ( 1973 ) identified similar prevalence of pca among groups ( 5 ) . on the contrary , gilland et al . ( 1998 ) found different patterns of incidence and mortality of pca among american indians , blacks , hispanics from new mexico and non - hispanic whites , with the lower incidence among indians ( 1 ) . although different incidences of pca among ethnic groups exist due to different screening methods and access to health care ( 13 ) , several exogenous risk factors may contribute to the disparity of risks , including dietary habits , lifestyle and genetic predisposition ( 16 ) . the association of prostate cancer , ingestion of saturated fat , bmi and physical activity was observed in many ethnic groups ( 14 ) , along with the association of the size of body , in particular waist - hip , with pca in chinese men ( 17 ) . changes in lifestyle and dietary habits have great impact , increasing three to seven times the incidence of pca in first generation of american japanese and chinese , whose fathers migrated to usa ( 18 , 19 ) . however , the impact of diet is still controversial and data related to indian nutritional status are rare . in men , testosterone is the main circulating androgen , with major role in male physiology , in particular prostate . we observed that yanomamis present lower levels of testosterone ( 414 ng / dl ) in relation to other ethnic groups ( 502/512 ng / dl ) , but still within normal limits ( 350 - 1000 ng / dl ) . we have also observed a particular difference of size and consistency of prostate during dr in indians in relation to non - indigenous patients . gland with a more fibroelastic consistency , sometimes not detectable during digital rectal exam in the indian population . we think that , more than isolated hormonal factors , the ingestion of several plants and the genetic background are the principal causes of this characteristic of physical exam of indians . the analysis of serum psa using different thresholds revealed that 5.8% of participants had total psa4.0 ng / ml and 8.7% > 2.5 ng / ml . in accordance to other studies ( 20 - 23 ) , we have observed a rise of psa levels with age in our population , indicating that the rise of psa with age of brazilian indians is in accordance to general population . in our casuistic abdominal circumference ( 90 cm is the threshold value ) did not correlated to lower urinary tract symptoms ( obstructive and/or irritative ) , as well as to prostatic cancer , in accordance do european results ( 24 , 25 ) . genetically , our data show that none patients of yanomami group presented the genotype pro / pro of p53 , compared to 2.02% of macuxi , 8.3% in other ethnic groups and 12.6% in the control group , highlighting the miscegenation of the genotype pro / pro of p53 . wu et al . demonstrated that genotypes arg / pro and pro / pro related to the susceptibility to pca in chinese men ( 26 ) , in accordance to quiones et al . in chilean patients ( 27 ) . however , henner et al . reported that the genotype pro / pro could be related to protection against pca in caucasian men ( 28 ) . genotypic divergence of yanomami population may be explained by intercrossing of consanguineous marriages , and the genes being transmitted from only one ancestral . another aspect is the subdivision of population in isolated groups , separated by geographic , political , socioeconomic , religious and cultural barriers , preventing the exchange of genes by interethnic marriages ( 29 ) . when we evaluated the genotypic profile results of gstp1 , again we observed difference between indians and non - indians . the frequency of variant genotypes ile / val and val / val is lower among indians , raising again the hypothesis of the above factors for p53 being related to such genotypic profile . among the yanomami studied , the homozygous genotype val / val was observed in only three cases ( 7.7% ) . a meta - analysis study of genotypes gstm1 , gstt and gstp1 including 11 studies ( 2.528 patients and 3.076 controls ) concluded that these three polymorphisms are not important factors for the susceptibility to pca ( 30 ) but indian populations were not represented . in our sample , the number of participants per ethnic group is relatively small and the estimates of race , ethnic group and comparison among groups were restricted to macuxis , yanomamis and  other ethnic groups  as a third group . on the other hand , this study so far is one with the biggest casuistic of amazon indians evaluated urologically , anthropometrically and genetically ( p53 codon 72 and gstp1 ) . although with a restrict number of controls ( n=87 ) , the results suggest differences of the genetic profile of indians , maybe related to risk - protection patterns that explain the low prostate volume and the relatively low incidence of prostatic diseases in these populations . limits of the study : although we had not compared dietary details with the ingestion of satured fat or industrial products among ethnical groups , it is evident that hunt meat is the basis of indian diet ; although the detailed comparison between ethnical groups more or less culturalized was obtained , the comparison with the control group of non - indigenous individuals was limited to genetic , age and tobacco use . new indian population studies are necessary to measure and follow the epidemiological modifications due to contact among indians and non - indians , in order to stablish health care guidelines , in particular preventive ones , directed to the new reality of the studied population . these new studies may reveal the impact of inheritance of detoxification genes as polymorphisms of gstp1 and tp53 , along with the recognition and elimination of toxic dietary products related to prostatic diseases . indians , in particular yanomamis , present low prostatic volume , lower bmi and different genotypic profile of gstp1 and tp53 codon 72 , although with similar psa and testosterone levels to other ethnic groups .
purpose to compare dietary , lifestyle , clinical , anthropometric , genetic and prostatic features of brazilian indians and non - indians ( amazon).methods 315 men , 228 indians and 89 non - indians , 40 years old were submitted to digital rectal examination , serum prostate specific antigen ( psa ) , testosterone , tp53 and gstp1 genotyping , anthropometric , lifestyle , dietary , personal and familial medical history . 
 prostatic symptoms were evaluated with the international prostate symptom score ( ipss).results macuxis and yanomamis represented 43.6% and 14.5% of indians respectively who spontaneously referred no prostate symptoms . 
 mean ipss was 7 , range 3 - 19 , with only 15% of moderate symptoms ( score 8 - 19 ) ; mean age was 54.7 years , waist circumference 86.6 cm , bmi 23.9 kg / m2 . 
 yanomamis presented both lower bmi ( 21.4 versus 24.8 and 23.3 , p=0,001 ) and prostate volume than macuxis and  other ethnic groups 
 ( 15 versus 20 , p=0.001 ) . 
 testosterone ( 414 versus 502 and 512 , p=0.207 ) and psa ( 0.48 versus 0.6 and 0.41 , p=0.349 ) were similar with progressive psa increase with aging . 
 val / val correlated with lower psa ( p=0.0361 ) . 
 indians compared to control population presented : - tp53 super representation of arg / arg haplotype , 74.5% versus 42.5% , p<0.0001 . 
 -gstp1 ile / ile 35.3% versus 60.9% ; ile 
 / val 45.9% versus 28.7% ; val / val 18.8% versus 10.3% ; p=0.0003.conclusions observed specific dietary , lifestyle , anthropometric and genetic profile for tp53 and gstp1 may contribute to brazilian indian population prostate good health .