Polymorphism in the P-glycoprotein drug transporter MDR1 gene in colon cancer patients.
OBJECTIVE
The P-glycoprotein, a product of MDR1 (multiple drug resistance 1) gene, is a membrane efflux pump localized in epithelial cells in the small and large intestine, a part of the gastrointestinal barrier that protects cells against xenobiotics from our diet, bacterial toxins, drugs and other biologically active compounds, possibly carcinogens. In the present study, an association of MDR1 gene polymorphism and the occurrence of colon cancer were evaluated.


METHODS
The study population consisted of 184 unrelated sporadic colon cancer patients and 188 healthy unrelated controls. Colon cancer patients were also subdivided into two subgroups, i.e., diagnosed before and after 50 years of age, and compared with age-stratified controls. The C3435T MDR1 gene polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism method.


RESULTS
The distribution of wild-type and mutated genotypes was similar in the colon cancer patients and in the healthy controls. However, when patients diagnosed before 50 years of age were compared with the healthy population, carriers of MDR1 3435TT genotype or 3435T allele were at 2.7-fold (P<0.05) and 1.7-fold (P<0.05) higher risk of the disease development, respectively.


CONCLUSIONS
Genetic testing for C3435T MDR1 gene polymorphism may be a suitable test to evaluate the risk for colon cancer in patients under 50 years of age.
Kurzawski
Mateusz
M
Department of Pharmacology, Pomeranian Medical University, Powstańców Wlkp. 72 Str, 70-111, Szczecin, Poland. mkurz@op.pl
Droździk
Marek
M
Suchy
Janina
J
Kurzawski
Grzegorz
G
Białecka
Monika
M
Górnik
Wanda
W
Lubiński
Jan
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1