title: Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers.
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 > 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).
  
  
  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.
authors.affiliation: Institute of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Campus Mitte, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Osswald
authors.forename: Andreas
authors.initials: A
authors.lastname: Johne
authors.forename: Gabriele
authors.initials: G
authors.lastname: Laschinski
authors.forename: Farhad
authors.initials: F
authors.lastname: Arjomand-Nahad
authors.forename: Uwe
authors.initials: U
authors.lastname: Malzahn
authors.forename: Julia
authors.initials: J
authors.lastname: Kirchheiner
authors.forename: Thomas
authors.initials: T
authors.lastname: Gerloff
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Przemyslaw M
authors.initials: PM
authors.lastname: Mrozikiewicz
authors.forename: Jury
authors.initials: J
authors.lastname: Chernov
authors.forename: Ivar
authors.initials: I
authors.lastname: Roots
authors.forename: Karla
authors.initials: K
authors.lastname: Köpke
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000375:Aging; D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012426:Russia; D012907:Smoking / Q000009:adverse effects*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1