Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers.
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.
Osswald
Elena
E
Institute of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Campus Mitte, Humboldt University of Berlin, Berlin, Germany.
Johne
Andreas
A
Laschinski
Gabriele
G
Arjomand-Nahad
Farhad
F
Malzahn
Uwe
U
Kirchheiner
Julia
J
Gerloff
Thomas
T
Meisel
Christian
C
Mrozikiewicz
Przemyslaw M
PM
Chernov
Jury
J
Roots
Ivar
I
Köpke
Karla
K
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*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1