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

• Published in: European journal of clinical pharmacology 2007-01, Vol.63 (1), p.9-16
• Main Authors: Osswald, Elena, Johne, Andreas, Laschinski, Gabriele, Arjomand-Nahad, Farhad, Malzahn, Uwe, Kirchheiner, Julia, Gerloff, Thomas, Meisel, Christian, Mrozikiewicz, Przemyslaw M, Chernov, Jury, Roots, Ivar, Köpke, Karla
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging; Alcohol Drinking - adverse effects; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Case-Control Studies; Colorectal cancer; Colorectal Neoplasms - etiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Humans; Life Style; Male; Middle Aged; Older people; Polymorphism, Genetic; Risk Factors; Russia; Smoking; Smoking - adverse effects; Tumors
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-006-0225-9

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. 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. 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 > or =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). 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.