MDR1 C3435T polymorphism and cancer risk: a meta-analysis based on 39 case-control studies.
Multidrug resistance 1 (MDR1) gene encodes the ATP-dependent cellular efflux pump P-glycoprotein (P-gp) which efflux of a variety of substances across the membrane. P-gp could serve a role in cancer etiology based on its physiological role of protecting cells from xenobiotics or metabolites. The C3435T (rs1045642) polymorphism of the MDR1 gene which could influence the P-gp expression and function have been implicated in the cancer risk. However, the results from the published studies on the association between this polymorphism and cancer risk are conflicting. To drive a more precise estimation of this association, we performed a meta-analysis of 39 case-control studies, including a total of 9,265 cancer cases and 13,502 controls. We used odds ratios (ORs) with their 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the MDR1 3435TT genotype were associated with an increased cancer risk than those with the CC (OR = 1.29, 95% CI: 1.10-1.51) or CT/CC (OR = 1.18, 95% CI: 1.04-1.34) genotypes, similar to the CT or CT/TT compared with the CC genotype. In the stratified analyses, the increased risks were more pounced among hematologic malignances (OR = 1.27, 95% CI: 1.10-1.46, P (heterogeneity) = 0.415), breast cancer (1.42, 1.04-1.94, 0.018), renal cancer (1.77, 1.28-2.46, 0.307), Caucasians (1.21, 1.07-1.38, 0.000) and population-based studies (1.20, 1.05-1.36, 0.000) in a dominant model. The results suggested that the MDR1 C3435T polymorphism may contribute to cancer risk.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Xiaojing
X
Sheng
Limei
L
Zhang
Na
N
Tong
Dewei
D
Luo
Meilin
M
Wang
Min
M
Xu
Zhengdong
Z
Zhang
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1