RESUMO
Background: This study aimed to evaluate for the first time whether certain genetic and clinical factors could serve as minimally invasive predictors of survival and toxicity to platinum-based chemotherapy in advanced lung adenocarcinoma. Methods: The study included 121 advanced lung adenocarcinoma patients treated with platinum-based dublets until progression or unacceptable toxicity. Response was evaluated using standard radiological methods and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Genotyping was performed using PCR-RFLP. Statistical significance was set at P < .05. Results: No significant influence of the examined polymorphisms on the occurrence of high-grade toxicity was detected. However, TP53 72Pro allele carriers were more prone to nausea (P = .037) and thrombocytopenia (P = .051). Anemia and neuropathy occurred more frequently in XRCC1 399Arg allele carriers (Pearson χ2 test, P = .025 and P = .004 respectively). RAD51 135CC carriers were significantly more prone to neutropenia (P = .027). Conclusions: A set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.
RESUMO
AIM: TP53 and DNA repair polymorphisms have been proposed as cancer risk factors. This study evaluated the usability of TP53 Arg72Pro single-nucleotide polymorphism, X RCC1 Arg399Gln and RAD51 G135C as a low-cost lung adenocarcinoma screening tool. PATIENTS AND METHODS: This case-control study included 78 atients with lung adenocarcinoma and 79 healthy matched controls. TP53, XRCC1 and RAD51 genotyping was done by PCR followed by restriction length polymorphism. Descriptive analyses included genotype and allelic frequencies and deviations of the frequencies from those expected under Hardy-Weinberg equilibrium were assessed using the χ2 test. The OR and 95% CIs were calculated as an estimate of relative risk, with significance set at p value <0.05. RESULTS: The TP53 codon 72 Pro allele and the XRCC1 codon 399 Arg allele in a homozygous state were associated with lung adenocarcinoma (p=0.037; OR (95% CI) 2.42 (1.10 to 5.31)), that is, p=0.037; OR (95% CI) 2.16 (1.08 to 4.33), respectively. Also, carriers of the TP53 codon 72 Pro allele and the XRCC1 codon 399 ArgArg genotype older than 50 showed an even higher risk of developing lung adenocarcinoma (p=0.03 in both cases). CONCLUSIONS: The TP53 codon 72 Arg allele and XRCC1 codon 399 Gln allele are likely to have a protective effect against lung adenocarcinoma, especially in individuals older than 50 years of age. XRCC1 and TP53 genotyping might be a useful low-cost tool for evaluating individual lung cancer risk, leading to earlier detection and management of this disease.
