lung cancer is one of the most common cancers in morocco and in the world and is the leading cause of cancer mortality in both males and females [ 1 , 2 ] . during the last few years , improvement in the knowledge of lung cancer molecular biology led to identification of several biological events crucial for tumor cell survival . in nonsmall - cell lung cancer ( nsclc ) , one of the most commonly genetic aberrations is conversion of the protooncogene kras to its activated oncogenic form . kras encodes low molecular weight gtpase binding proteins that regulate cell growth , differentiation , and apoptosis . mutations of kras are associated with impaired gtpase activity , causing increased mitogenic ras signaling . mutations in kras gene occur more frequently ( 2030% ) in adenocarcinoma and less frequently ( about 7% ) in squamous - cell carcinoma and are usually associated with a history of smoking . the incidence of kras mutation is ethnicity dependent with a higher proportion in african americans and white caucasians ( 2030% ) than in asians ( 520% ) [ 57 ] . however , such information is still lacking in some other races , such as north african patients . typically , kras mutations are a point mutation in the gene replacing an amino acid at positions 12 , 13 , or 61 . together , these two mutations account for nearly 95% of all kras mutations in lung cancer . the g12c mutation in codon 12 is by far the most frequent mutation in nsclc [ 810 ] . the main goal of this study was to report the frequency and spectrum of kras mutations in unselected group of moroccan lung adenocarcinoma patients . in addition , we have examined the relationship between the mutations and some parameters , including gender and smoking status . data of all lung adenocarcinoma samples were collected from four pathology laboratories in morocco between november 2010 and august 2012 . the participating laboratories were nations - unies pathology center , rabat ; hassan pathology center , rabat ; agdal pathology center , rabat ; casapath pathology center , casablanca . all of these laboratories outsource kras mutation testing ( molecular biology laboratory in paris , france ) and perform more than 90% of all tests requested in morocco . the histological diagnosis of adenocarcinoma was verified using the pathology report provided by participating laboratories . never smokers were defined as individuals who reported smoking fewer than 100 cigarettes in their lifetime . kras mutations in codons 12 and 13 of exon 2 were analyzed using conventional dna sequencing . the ethics committee approval was not necessary for this study , since all mutation tests were part of the routine diagnostic procedure and all patient and tumor characteristics were collected anonymously . the potential associations of kras mutation with age , gender , and smoking status were analyzed using fisher 's exact test . the study population consisted of 77 men ( 66% ) and 40 women ( 34% ) , with a median age of 59 years ( range : 37 to 87 years ) . a total of 11 kras mutations were found in this series of 117 patients ( 9% ) . kras mutations were identified in 13% of smokers ( 9/68 ) and 4% of never smokers ( 2/49 ) . there were 13% of male ( 10/77 ) and 2% of female ( 1/40 ) with kras mutations . in the population with kras mutations , there was a trend towards more male than female compared to patients with wild type kras ( 91% versus 63% , p = 0.06 ) but this did not reach statistical significance . the frequency of smokers in patients with tumors having kras mutations was higher than that observed in patients without mutations ( 82% versus 56% , p = 0.08 ) but also this did not reach statistical significance . all kras mutations were located at codon 12 , with the exception of a single patient in which kras was mutated at codon 13 . the g12c mutation was the most frequent kras mutation ( 73% ) in this series ( table 3 ) . in the present series , kras mutations were identified in 11 of 117 moroccan patients ( 9% ) . to the best of our knowledge , this study represents the first study to date reporting kras mutation rate in north african and arabs populations . some previous studies have demonstrated a genetic divergence of kras mutation rates according to ethnicity [ 1118 ] . indeed , kras mutations rate in caucasian ( 2637% ) and african - american ( 1737% ) patients is much higher than that in east - asian population ( 611% ) . kras mutation frequency in moroccan patients , as reported in this study , was comparable with the frequency observed in east - asian population ( table 4 ) . in the population with kras mutations , we found a trend towards more male than female compared to patients with wild type kras ( 91% versus 63% , p = 0.06 ) . this did not reach statistical significance , probably due to the low number of patients with kras mutations in the present study . however , these results are in keeping with some published reports showing a trend towards more mutations in males [ 19 , 20 ] . in this study , the higher frequency of kras mutations among smokers ( 82% ) supports data from some previous studies . for example , ahrendt et al . reported a strong positive association between presence of kras mutations and smoking . a meta - analysis of kras mutations in nsclc reported a frequency of 26% in tumors of current / former smokers and 6% in tumors of never smokers . on the other hand , kras mutations have been detected in a significant proportion of never smoker lung adenocarcinoma patients , with an incidence up to 15% , and thus remain not rare in this subpopulation . in lung adenocarcinomas , the majority of kras mutations have been identified in codons 12 and 13 . in our subjects , the distribution of mutations of kras at codons 12 ( 10/11 ( 91% ) ) and 13 ( 1/11 ( 9% ) ) appear to be comparable with the frequency of the other studies [ 23 , 24 ] . furthermore , the g12c mutation was the most frequent kras mutation ( 73% ) confirming previous results [ 810 ] . transversions ( substituting a pyrimidine base for a purine base or vice versa ) are more common than transitions ( substituting purine for purine or pyrimidine for pyrimidine ) . kras mutations observed in smokers are more likely to be transversions unlike the transitions more common in patients with no history of cigarette smoking . indeed , the etiology of g  t transversion in lung cancer has been attributed to the exposure to polycyclic aromatic hydrocarbons ( pah ) present in tobacco smoke . in the present study , 89% of smokers ( 8/9 ) had a transversion mutation supporting these data . till date , the clinical applicability of the kras mutation is limited . while some studies suggested that mutant kras may have a potential negative prognostic effect and could be predictive of lack of response to chemotherapy and epidermal growth factor receptor ( egfr ) inhibitors , other studies failed to confirm this result [ 6 , 26 ] . however , previous studies have shown that egfr and kras mutations are mutually exclusive [ 5 , 19 ] . kras may therefore have a role as part of an efficient testing algorithm . in summary , the present study revealed that kras mutation frequency in moroccan patients was comparable with the frequency observed in east - asian population . in keeping with the literature , further studies , in larger numbers of patients , are needed to confirm these findings .
background . in lung adenocarcinoma , the frequency of kras mutations is ethnicity dependent with a higher proportion in african americans and white caucasians than in asians . 
 the prevalence of these mutations among north africans patients is unknown . 
 the objective of this study was to report the frequency and spectrum of kras mutations in a group of moroccan lung adenocarcinoma patients . 
 methods . 
 tumor specimens from 117 moroccan patients with lung adenocarcinoma were selected to determine frequency and spectrum of kras mutations . 
 kras mutations in codons 12 and 13 of exon 2 were analyzed using conventional dna sequencing . 
 results . the overall frequency of the kras mutations was 9% ( 11/117 ) . in the population with kras mutations , there was a trend towards more male ( p = 0.06 ) and more smokers ( p = 0.08 ) compared to patients with wild type kras . 
 kras mutations were located at codon 12 in 10 out of 11 patients ( 91% ) . 
 the g12c mutation was the most frequent kras mutation ( 73% ) . 
 conclusion . 
 this is the first study to date examining the frequency and spectrum of kras mutations in lung adenocarcinomas in north african and arab populations . 
 kras mutation frequency in moroccan patients was comparable with the frequency observed in east - asian population . 
 kras mutations are more likely observed in males and smokers and to be transversions . 
 further studies , in larger numbers of patients , are needed to confirm these findings .