Correlation Of Gene Polymorphisms In TGF?1 Signaling Pathway Genes And Radiation-Induced Rectal Injury In Cervical Cancer Patients

Objective: To investigate the correlation of single nucleotide polymorphisms in TGF?1 signaling pathway genes TGF?1, SMAD3 as well as SMAD4 and the occurrence of acute and chronic radiation-induced rectal injury of patients with cervical cancer in Chinese population.Methods and Materials: The study population consists of 121 cervical cancer patients, who were treated with radiation therapy(RT) to the pelvis before.RT-induced acute and chronic rectal injury was scored using the toxicity criteria of the Radiation Therapy Oncology Group(RTOG) and the European Organization for Research and Treatment of Cancer(EORTC). Genotypes were detected by the first-generation sequencing technology- dideoxy chain termination method.Univariate and multivariate two yuan logistic regression analysis were employed to assess the association between the single nucleotide polymorphisms in TGF?1(rs11466313, rs1800468, rs1800469, rs1800470, rs1800471), SMAD3(rs12901499)as well as SMAD4(rs12456284) and the risk of developing acute or chronic radiation rectal injury.Results: SNP in SMAD4 gene(rs12456284) was significantly associated with the occurance of chronic radiation rectal injury. In multivariate logistic regression analysis, patients carrying AG and GG genotypes have a significantly lower risk of developing chronic rectal injury(OR=0.308, p=0.012 and OR=0.121, p=0.007,respectively), but with acute rectal injury, there was no significant correlation(p?0.05).No significant association was found between the TGF?1(rs11466313, rs1800468,rs1800469, rs1800470, rs1800471) as well as SMAD3(rs12901499) and the development of acute or chronic radiation rectal injury(p?0.05). In addition, the total radiation dose ?85Gy significantly increased the risk of chronic radiation rectal injury(OR=2.406, p=0.036).Conclusions: The present study shows that SNP in SMAD4 gene(rs12456284) was associated with the occurance of chronic radiation rectal injury in Chinese cervical cancer patients. the AG and GG genotypes may be a protective factor. The total radiation dose ?85Gy is another risk factor of developing chronic radiation rectal injury.