P21 [Waf1/Cip1] gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in northeastern iran: a preliminary study

The incidence of esophageal squamous cell carcinoma [ESCC] is very high in northeastern Iran. However, the genetic predisposing factors to ESCC in this region have not been clearly defined. The P21 [waf1/cip1] gene is involved in the arrest of cellular growth, as induced by the p53 tumor suppressor gene. Two polymorphisms of p21 gene in codon 31 [p21 C98A, dbSNP rs1801270] and the 3'UTR [p21 C70T, dbSNP rs1059234] ma-y affect protein expression and play a role in cancer susceptibility. The present study aimed to investigate the association of p21 polymorphisms in codon 31 and the 3'UTR, and cigarette smoking on the risk of ESCC in northeastern Iran. A case-control study was carried out to detect the p21 polymorphism in the 3'UTR and codon 31 of samples from 126 ESCC cases and 100 controls from 2006 to 2007. There were no significant differences of age and sex between cases and controls. Genotyping of p21 polymorphisms were determined with the PCR-RFLP method. Conditional logistic regression was used to adjust for potential confounders. None of the p21 genotypes were significantly associated with risk of ESCC, even after adjusting for age and gender [P=0.52, OR=1.24; 95%CI: 0.63-2.42]. However, the presence of these polymorphisms in combination with cigarette smoking had a synergistic interaction in ESCC carcinogenesis in northeastern Iran [P=0.02, OR=8.38; 95%CI: 1.03-67.93]. Our data suggests that these two p21 polymorphisms, both alone and in combination, are not genetic susceptibility biomarkers for ESCC. However, their interaction with cigarette smoking may influence the susceptibility to ESCC development in northeastern Iran

Prevalence of esophageal cancer risk factors among Turkmen and non-Turkmen ethnic groups in a high incidence area in Iran

Golestan Province in north-eastern Iran has one of the highest incidence rates for esophageal squamous cell carcinoma [ESCC] worldwide. Earlier studies have reported higher incidence rates in the areas of Golestan which are mainly inhabited by individuals of the Turkmen ethnic group. However, it is not clear whether in those areas the incidence among Turkmens is higher in comparison to non-Turkmens. Some previous studies have suggested that environmental factors might play a more essential role in ESCC carcinogenesis in Golestan than a genetic background. If environmental factors instead of a genetic background are the major risk factors, therefore the prevalence of known environmental risk factors would not significantly differ among ESCC cases of different ethnic groups. To investigate the role of environmental factors versus genetic background by using the above concept, we have compared the prevalence of known risk factors for ESCC among Turkmen and non-Turkmen ESCC cases. Study participants were histopathologically proven ESCC cases from Golestan Province. They were recruited in the study from December 2003 to June 2007. The prevalence of the most important known risk factors for ESCC in Turkmen and non-Turkmen ESCC cases was compared using Chi-squared and Fisher's exact tests. Of 300 ESCC cases recruited in the study, 171 [57.0%] and 129 [43.0%] cases were Turkmen and non-Turkmen, respectively. In the majority of the investigated risk factors which included tobacco, nass, and opium use, hot and extremely hot tea consumption, as well as decreased levels of education; there was no significant difference between Turkmen and non-Turkmen ESCC cases in the prevalence of exposure. Our findings support the suggestion that a substantial difference between Turkmens and non-Turkmens in terms of genetic susceptibility to ESCC is unlikely. Nevertheless, the moderate effect of genetic factors cannot be ruled out. Further studies to investigate potential environmental and genetic risk factors of ESCC in Golestan and the interaction between environmental and genetic factors are warranted