Carcinogenesis Advance Access published online on May 10, 2007
Carcinogenesis, doi:10.1093/carcin/bgm113
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BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma
1 Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences
2 State Key Laboratory of Oncology in Southern China, Cancer Center
3 Department of cardiology, the Fifth Affiliated Hospital, School of public health, Sun Yat-Sen University, P. R. China
4 Department of Medical Statistics and Epidemiology, School of public health, Sun Yat-Sen University, P. R. China
* Corresponding author: Shi-Mei Zhuang, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, P. R. China. Tel: +86-20-84112164; Fax: +86-20-84112169; E-mail: lsszsm{at}mail.sysu.edu.cn
To date, the biological significance of BCRP G34A and C421A polymorphisms is largely unknown. Analysis of these two polymorphisms in 156 diffuse large B-cell lymphoma (DLBCL) patients and 376 control subjects revealed an increased risk of DLBCL associated with variant BCRP 421 genotypes (CA and AA), when compared with the wild type CC genotype (OR = 1.49, 95% CI 1.02-2.17, P = 0.042). Moreover, the increased risk was more evident in younger patients (
50 years, OR = 2.14, 95% CI 1.25-3.68, P = 0.006). Further evaluation for the association of these polymorphisms with overall survival of DLBCL showed that patients with 34AA alleles displayed worse survival compared with those carrying GG/AG genotypes (HR = 3.69, 95% CI 1.56-8.71, P = 0.001). Significant association between 421CC genotypes and poorer survival of DLBCL was observed in patients younger at diagnosis ( 50 years, HR = 5.80, 95% CI 1.16-28.90, P = 0.015) or with bulky tumor (HR = 4.36, 95% CI 1.04-18.31, P = 0.027). Furthermore, we found the combined effects of BCRP G34A and C421A on the overall survival. Compared with patients carrying BCRP 34(GG+GA)421(AA+CA) genotype, the individual with 34AA421CC displayed the worst survival (HR = 7.55, 95% CI 2.36-24.17, P = 0.001), while those with 34(GG+GA)421CC and 34AA421(AA+CA) combinations showed the intermediate survival. These results suggest that the BCRP G34A and C421A polymorphisms are associated with the risk and survival of DLBCL. Our finding warrants further investigations on the association of BCRP polymorphisms with susceptibility and clinical outcome of cancer.
Key Words: BCRP • single nucleotide polymorphism • diffuse large B-cell lymphoma • risk • survival
Present Address: Tumor Hospital of Fudan University, P. R. China Received March 15, 2007; revised April 29, 2007; accepted May 6, 2007.