Significant association between ABCB1 gene C3435T polymorphism and breast cancer risk

Abstract

We read with great interest a recent article entitled ‘‘Association between two polymorphisms of ABCB1 and breast cancer risk in the current studies: a meta-analysis’’ by Lu et al. [1] published online in Breast Cancer Research and Treatment. The meta-analysis by Lu et al. was aimed to derive a more precise assessment of this relevance between two ABCB1 polymorphisms (C3435T and rs2214102) and breast cancer susceptibility. A total of seven studies were included in the meta-analysis [2–8]. The results indicated that the ABCB1 C3435T polymorphisms was not associated with increased risk of breast cancer (T vs. C: OR = 1.15, 95% CI = 0.89–1.48; CT vs. CC: OR = 1.12, 95% CI = 0.86–1.46; TT vs. CC: 1.30, 95% CI = 0.79–2.15; the domain model: 0.80, 95% CI = 0.63–1.02; the recessive model: 0.83, 95% CI = 0.57–1.22). However, in Caucasian women the T allele contrast model (OR = 1.26, 95% CI = 1.04–1.52) and the TT genotype (OR = 1.48, 95% CI = 1.04–2.11) were associated with increased cancer risk. Thus, the authors concluded that ABCB1 C3435T polymorphism did not significantly correlated with breast cancer risk. However, the conclusion and some methodological issues should be addressed concerning this meta-analysis. First, non-English studies were excluded in the study. Unpublished studies and studies in abstract form were not explicitly mentioned in Materials and methods. Thus, selection, language, and publication biases are potential threats to the validity of the reported meta-analysis due to the limited search strategy. Second, there were incorrect data provided by Lu et al. For example, the genotypes of ABCB1 C3435T (study by George et al.) were 8 of CC and 39 of TT, not 39 of CC and 8 of TT in cases in Table 2. Genotypes of this polymorphism were 15 of CC and 21 TT, not 21 of CC and 15 TT in controls. Here, we retrieved the correct data from the published articles and conducted a new meta-analysis (Table 1). Based on our present results, there were significantly increased risks of breast cancer (OR = 1.66, 95% CI = 1.24–2.21, Pheterogeneity = 0.21 for TT vs. CC; OR = 1.41, 95% CI = 1.10–1.81, Pheterogeneity = 0.14 for the domain model and OR = 1.46, 95% CI = 1.05-2.04, Pheterogeneity = 0.14 for the recessive model) in population with ABCB1 C3435T polymorphism. Finally, the only study [3] derived from Hardy–Weinberg equilibrium was not excluded when the ORs of different studies were combined. Actually, when the study was excluded, the results were in agreement with the findings from foregoing analysis (TT vs. CC: OR = 1.83, 95% CI: 1.32–2.55, Pheterogeneity = 0.23; the domain model: OR = 1.46, 95% CI: 1.12–1.90, Pheterogeneity = 0.84; the recessive model: OR = 1.58, 95% CI: 1.08–2.32, Pheterogeneity = 0.13). Although the authors stated that information was carefully extracted from all eligible publications independently by two of the authors, some incorrect data occurred in this review. Therefore, we believe that the results of this study need to be interpreted with caution given the many methodological deficiencies and incorrect data extracted from articles in the review. Our findings were in the opposite direction to those observed in the study by Lu et al. In general, the results should strongly support a significant association between ABCB1 gene C3435T polymorphism and the risk of breast cancer. Especially, the raw data J. Wang (&) B. Wang J. Bi Department of Oncology, General Hospital, Jinan Command of the People’s Liberation Army, Shifan Street 25, Tianqiao District, Jinan, China e-mail: ggjun2005@126.com