Tohoku J. Exp. Med., 2016 April, 238(4)

Association of Single Nucleotide Polymorphisms in the Apoptosis-Related Genes TP63 and CD40 with Risk for Lung Cancer in a Chinese Han Population

WENJUN TANG,^1,3 LI XUE,² QIXING YAN,³ SHAOXI CAI,¹ YUJIE BAI,² LI LIN,³ BILIN LIN,³ MINGLONG HUANG,³ GUOHUI YI² and HUI LI³

¹Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China
²Science Research Center, Hainan Medical College, Haikou, Hainan, P.R. China
³Department of Gerontology Medicine, General Hospital of Hainan Land Reclamation, Haikou, Hainan, P.R. China

Apoptosis plays a critical role in tumorigenesis. TP63 inhibits the pro-apoptosis function of TP53, and CD40 increases expression of anti-apoptotic proteins. Two single nucleotide polymorphisms (SNPs), rs6790167 (g243059A>G) in intron 9 of TP63 and rs1535045 (g6194C>T) in intron 1 of CD40 respectively, may affect the susceptibility of lung cancer. To evaluate the association of these SNPs with lung cancer, we performed a case-control study with 258 patients, including 149 adenocarcinoma and 47 small cell lung cancer, and 270 controls. Genotyping was conducted using allele-specific polymerase chain reaction and pyrosequencing. We found that rs6790167 and rs1535045 are associated with the risk of lung adenocarcinoma (P = 0.048) and small cell lung cancer (P = 0.019), respectively. Non-smoking males carrying the GG genotype of rs6790167 had higher risk for lung adenocarcinoma than individuals carrying the AA genotype (OR = 7.58, 95% CI: 2.43-23.65). Compared to the TT genotype of rs1535045, non-smoking women with the CC genotype had higher risk for lung adenocarcinoma (OR = 4.20, 95% CI: 1.34-13.12). After stratified analysis based on clinical characteristics, the frequency of the CC genotype of rs1535045 was higher in patients at I-II stages (P = 0.013) or patients whose tumor markers were negative (P = 0.003). Individuals carrying both the GG genotype of rs6790167 and the CC genotype of rs1535045 were associated with significantly higher risk for lung adenocarcinoma. Thus, the polymorphisms in the TP63 and CD40 genes are associated with lung cancer in a Chinese Han population.

keywords —— apoptosis; CD40; lung cancer; single nucleotide polymorphism; TP63

© 2016 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2016, 238, 279-286

Correspondence: ShaoXi Cai, M.D., Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1023 Shatainan Road, Baiyun District, Guangzhou, Guangdong 510515, China.

e-mail: caishaox@fimmu.com

YuJie Bai, M.D., Science Research Center, Hainan Medical College, No.3 Xueyuan Road, Longhua District, Haikou, Hainan 571199, China.

e-mail: yujiebai@163.com