Abstract
Background and ObjectiveOverexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients treated with platinum-based chemotherapy.Materials and MethodsTwo hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP) methods.ResultsThe incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (−1195G/A) polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26–4.84) and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28–6.20). No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39–0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39–0.94, respectively) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14–2.56 and P value = 0.025; OR = 1.65; 95%CI = 1.06–2.57, respectively).ConclusionThis investigation for the first time suggested that polymorphism in COX-2 rs689466 may be a potent bio-marker in predicting severe hematologic toxicity in NSCLC patients after platinum-based chemotherapy.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death in the world and NSCLC comprises the most common form of it [1,2]
The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (21195G/A) polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26–4.84) and the significance still existed after the Bonferroni correction
The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; odds ratios (OR) = 0.59; 95% confidence intervals (95%CI) = 0.39– 0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39–0.94, respectively) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14–2.56 and P value = 0.025; OR = 1.65; 95%CI = 1.06–2.57, respectively)
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death in the world and NSCLC comprises the most common form of it [1,2]. Platinum-based regimens have been used as the standard firstline chemotherapy in NSCLC patients [3,4] while the unpredictable and occasionally serious side effects, especially hematologic toxicity, continue to be an intractable problem. Searching of predictive markers that can identify patients who will benefit significantly from chemotherapy with minimal toxicity is a necessary and promising job in lung cancer research. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum-based treatment. Caspase-3(CASP3), an apoptosis-related gene, was reported to be associated with severe hematologic toxicity risk [6]. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients treated with platinum-based chemotherapy
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