Background: P-glycoprotein, the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of environmental toxins and xenobiotics. Epidemiological studies have evaluated the association between MDR1 C3435T polymorphism and cancer susceptibility. However, published data are still inconclusive.
Methods: To derive a more precise assessment of this relevance, we performed a meta-analysis, up to September 2010, of 5,196 cases with different cancer types and 6,827 controls from 34 published case-control studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for MDR1 C3435T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate.
Results: The overall results suggested that the variant was associated with a moderately increased cancer risk in all comparison models tested (OR = 1.26, 95% CI: 1.06-1.50 for TT vs. CC; OR = 1.19, 95% CI: 1.04-1.37 for CT vs. CC; OR = 1.15, 95% CI: 1.01-1.32 for recessive model; OR = 1.21, 95% CI: 1.06-1.38 for domain model, and OR = 1.14, 95% CI: 1.04-1.26 for allele contrast). In the subgroup analysis by cancer types, significant associations were found in breast cancer (OR = 1.66, 95% CI: 1.24-2.21 for TT vs. CC; OR = 1.44, 95% CI: 1.14-1.82 for recessive model; OR = 1.41, 95% CI: 1.10-1.81 for domain model; and OR = 1.31, 95% CI: 1.13-1.52 for allele contrast) and renal cancer (OR = 1.99, 95% CI: 1.37-2.90 for TT vs. CC; OR = 1.74, 95% CI: 1.25-2.42 for domain model; OR = 1.43, 95% CI: 1.09-1.88 for recessive model; and OR = 1.40, 95% CI: 1.17-1.68 for allele contrast). However, no significant associations were found in colorectal cancer, gastric cancer, and acute lymphoblastic leukemia for all genetic models. In the ethnicity subgroup analysis, a significant association with cancer among Caucasians was found under the dominant model, homozygote comparison, CT versus CC comparison, and allele comparison.
Conclusions: In summary, this meta-analysis suggests that the MDR1 C3435T polymorphism is associated with cancer susceptibility, increasing the risk of breast and renal cancer.