Abstract
Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.
Highlights
Lung cancer is the leading etiology of cancer death in both males and females with a 1.6 million deaths worldwide in 2013 [1]
The Carbonic anhydrase 9 (CA9) single nucleotide polymorphism (SNP) rs2071676 AG + GG was correlated to a lower tumor stage and lower risk for developing lymph node metastasis in lung carcinoma accompanied by wide type of epidermal growth factor receptor (EGFR)
The appearance of CA9 SNP rs2071676 is negatively associated with the rate of EGFR
Summary
Lung cancer is the leading etiology of cancer death in both males and females with a 1.6 million deaths worldwide in 2013 [1]. The lung adenocarcinoma accounts for about 30%–50% of all lung cancers and is predominant in the male population [2]. In the Eastern Asian population, the incidence lung cancers was 190.63 per 100,000 person-years in China [3], while a numerically lower rate of lung cancers was found in Taiwan with the incidence of 49.86 per 100,000 person-years [4]. Percent of all the lung cancers worldwide (including Japan and Hong Kong) and is predominant in the male population [2]. 54% in previous research [4,5], and a lower smoking rate, earlier clinical T-status, as well as greater metastasis tendency was observed in lung adenocarcinoma compared to lung squamous cell carcinoma in Taiwanese [5]. The adjuvant of target therapy can elevate the longer progression-free survival and overall survival compared to the traditional management only [8]
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