Carcinogenesis Advance Access originally published online on May 10, 2007
Carcinogenesis 2007 28(8):1740-1744; 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
4 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou 510275, P. R. China
5 Present address: Tumor Hospital of Fudan University, Shanghai, 200032, P. R. China
* To whom correspondence should be addressed. Tel: +86 20 84112164; Fax: +86 20 84112169; Email: lsszsm{at}mail.sysu.edu.cn
To date, the biological significance of breast cancer resistance protein (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 [odds ratio = 1.49, 95% confidence interval (CI) 1.02–2.17, P = 0.042]. Moreover, the increased risk was more evident in younger patients (
50 years, odds ratio = 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/GA genotypes [hazard ratio (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.
Abbreviations: BCRP, breast cancer resistance protein; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism
Received March 15, 2007; revised April 29, 2007; accepted May 6, 2007.