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M. Cavic



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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-007 - TP53 and DNA-Repair Gene Polymorphisms as Risk Factors for the Development of Advanced Lung Adenocarcinoma in Serbia (ID 9060)

      09:30 - 16:00  |  Author(s): M. Cavic

      • Abstract

      Background:
      TP53 and DNA repair genes polymorphisms have been proposed as clinically significant cancer risk factors. The TP53 gene, coding for a known tumor suppressor, is found to be mutated in over 30% of human cancers. Impaired DNA repair efficiency caused by differences in expression, methylation and polymorphisms of DNA repair genes XRCC1 and Rad51 is likely to affect cancer occurence. This study aimed to evaluate the association of the TP53 Arg72Pro single-nucleotide polymorphism (SNP) (rs1042522), XRCC1 Arg399Gln SNP (rs25487) and Rad51 G135C SNP (rs1801320) with the occurrence of lung adenocarcinoma in Serbia, both individually and in combination.

      Method:
      This case-control study included 65 advanced lung adenocarcinoma patients treated at two Institutes in Serbia, stage IIIB or IV, and ECOG performance status 0, 1 or 2, and 68 healthy matched controls. All subjects were of Caucasian descent. TP53, XRCC1 and Rad51 genotyping was done by polymerase chain reaction followed by restriction length polymorphism (PCR-RFLP). Statistical analysis was performed using the Chi-square test and descriptive analyses included genotype and allelic frequencies. Deviations of the genotype frequencies from those expected under Hardy-Weinberg equilibrium were assessed using the χ2 test. The odds ratio (OR) and 95 % confidence intervals (CI) were also calculated as an estimate of relative risk, with significance set at p < 0.05 for all analyses.

      Result:
      The frequencies of XRCC1 alleles in patients vs. controls were 0.75 vs. 0.6 for Arg, and 0.25 vs. 0.4 for Gln. XRCC1 Arg allele was significantly associated with the development of lung adenocarcinoma only in the recessive model [p=0.019; OR (95% CI) = 2.47 (1.21 - 5.05)]. The frequencies of Rad51 alleles in patients vs. controls were 0.78 vs. 0.76 for G, and 0.22 vs. 0.24 for C. The frequencies of TP53 alleles in patients vs. controls were 0.52 vs. 0.63 for Arg, and 0.48 vs. 0.37 for Pro. We found no statistically significant associations of Rad51 and TP53 polymorphisms with lung adenocarcinoma. Investigating all possible gene-gene interactions, we also found no statistically significant associations with lung adenocarcinoma.

      Conclusion:
      In this study, homozygous carriers of the XRCC1 Arg allele were found to be more susceptible to the development of lung adenocarcinoma during lifetime. Thus, XRCC1 genotyping might be useful as an additional tool for predicting individual lung cancer risk