Abstract LB-449: The relationship between CHRNA5 gene polymorphism and the strength of nicotine addiction in lung cancer, COPD and healthy smokers

Abstract

Introduction. A rare variant of chromosomal region 15q25.1, marked by rs16969968 (substitution 1354G>A or D398N in CHRNA5 gene), was found to be associated with increased lung cancer risk and nicotine dependence appearance. We attempted to confirm the relationship between polymorphism of gene for nicotine acetylocholine receptor A subunit 5 (CHRNA5) and stage of nicotine dependence measured by the result of Fagerström test and cotinine level in serum in lung cancer, COPD and healthy smokers. Methods. Polymorphism of CHRNA5 gene was analised using PCR-RFLP method in the group of 97 lung cancer patients, 99 COPD patients and 98 healthy volunteers. The Fagerström Test for Nicotine Dependence was used as a standard instrument for assessing the intensity of this physical addiction. Cotinine serum level was measured using ELISA method. Results. In all analyzed subjects, the frequency of AA, AG and GG genotypes were 11%, 47% and 42%, respectively. The polymorphism of CHRNA5 gene does not have a significant influence on the elevated risk of lung cancer and COPD. The presence of GG genotype decreased the risk of strength of nicotine addiction (HR=0.238, 95%CI:[0.066–0.857], p<0.05). We observed that allele A was presented more frequently in the subjects with high level of nicotine dependence and in the subjects with early (<25 years) onset of addiction (p<0.05). Moreover, cotinine serum level significantly correlated with results of Fagerström test (p<0.001). The carriers of allele A expressed significantly higher level of serum cotinine when compared with the carriers of GG genotype (p=0.05). Conclusion. In the presented abstract we report for the first time the relationship between the polymorphism of CHRNA5 gene and the strength of nicotine addiction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-449. doi:10.1158/1538-7445.AM2011-LB-449

Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer

“…Six meta-analyses have evaluated the influence of ERCC1 C118T polymorphism [11][12][13]33,101,102] and the two largest (23 studies/3231 patients and 21 studies/1281 patients, respectively), have not found any association between the ERCC1 C118T polymorphism and ORR (OR=0.94; CI95%=0.72, 1.23; I 2 =60%; Pheterogeneity <0.01; CT/TT vs CC and OR=0.95; CI95%=0.85, 1.06; I 2 =66.90%; Pheterogeneity=0.386; CT/TT vs CC) [13,102]. The same contradictory results have been reported in the case of PFS and OS, with some studies finding an association of the CC genotype with a better outcome and others reaching opposite conclusions [13,49,70,72,75,[77][78][79][80][81][82][83][84]96]. Finally, a meta-analysis including 13 studies, found a significant association of ERCC1 C118T polymorphism with a longer OS (OR=1.26; CI95%=1.02, 1.55; I 2 =67%; Pheterogeneity<0.01; CT/TT vs CC) but not with PFS (OR=1.23; CI95%=0.90, 1.69; I 2 =70.7%; Pheterogeneity <0.01; CT/TT vs CC) [13].…”

“…Regarding ERCC1 C118T, its association with clinical outcome to platinum-based chemotherapy remains unclear (Table 1) [13,24,44,49,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][92][93][94][95][96][97][98][99][100], with some studies reporting better overall response rate (ORR) in patients carrying the C allele [49,[69][70][71][72], and others in patients with the TT genotype [44,[73][74][75][76][77]. Six meta-analyses have evaluated the influence of ERCC1 C118T polymorphism [11][12][13]33,…”