Jun Wang1, Baocheng Wang, Jingwang Bi, Kainan Li, Jianshi Di. 1. Department of Oncology, General Hospital, Jinan Command of the People's Liberation Army, Shifan Street 25, Tianqiao District, Jinan 250031, China. ggjun2005@126.com
Abstract
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.
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 MDR1C3435T 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 MDR1C3435T 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 MDR1C3435T polymorphism is associated with cancer susceptibility, increasing the risk of breast and renal cancer.
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