Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers

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Abstract

Objective: The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. Methods: Two hundred and eighty-five colorectal cancer patients and 275 controls from five hospitals in the European part of Russia were genotyped for the polymorphisms -129T > C (rs3213619) in exon 1b, 2677G > T/A (rs2032582), and 3435C > T (rs1045642) in this population-based case-control study. Genotype-phenotype analysis was performed with simultaneous consideration of lifestyle risk factors. Results: Our analysis confirmed the preponderate impact of smoking on colorectal cancer development. The risk of heavy smokers (≥60 pack years) to develop colorectal cancer by far exceeded that of lifelong non-smokers (OR = 3.9, 95% CI: 1.4 to 10.6). Smoking is a more potent risk factor than is the genetic influence of MDR1 in our study. However, a smoking and age-stratified analysis, revealed a statistically significant association between MDR1 genotypes and colorectal cancer in life-long non-smokers with an age ≥63 years (the median age in our sample). The association was stronger for rectal cancer than for colon cancer. Patients who carried the genotypes (-129TT; 2677GG; 3435CC) or (-129TT; 2677TT; 3435TT) developed more frequently colorectal cancer than others (OR = 3.9; 95% CI: 2.0 to 7.7). Conclusions: Our results show that the interaction of genetic and lifestyle risk factors should be taken into account to elucidate the genetic influence of MDR1 variability on cancer susceptibility. © 2006 Springer-Verlag.

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Osswald, E., Johne, A., Laschinski, G., Arjomand-Nahad, F., Malzahn, U., Kirchheiner, J., … Köpke, K. (2007). Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers. European Journal of Clinical Pharmacology, 63(1), 9–16. https://doi.org/10.1007/s00228-006-0225-9

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