ABCB1 gene polymorphisms and expression of P-glycoprotein and long-term prognosis in colorectal cancer.

BACKGROUND

P-glycoprotein (Pgp), encoded by the ATP-binding cassette B1 (ABCB1) gene, is an efflux transporter located on the luminal side of intestinal epithelial cells, which protects the gut from endogenous and exogenous toxins. The association of two ABCB1 polymorphisms with the occurrence of colon cancer and long-term prognosis was evaluated in a selected patient population. The expression of Pgp in neoplastic and normal intestinal mucosa was also studied.

PATIENTS AND METHODS

Archival material from 51 patients, in Dukes stage B2 or C, treated for 6 months with 5-fluorouracil plus leucovorin was retrieved. The G2677T and C3435T polymorphisms were studied and immunohistochemical analysis of the tumor and adjacent normal tissue was performed.

RESULTS

The distribution of wild-type and polymorphic genotypes was similar in the patients and controls and in the patients who relapsed and those who remained event-free for 5 years. Cox proportional hazard model indicated an increased probability of relapse for older patients (p = 0.042) and C stage tumors (p = 0.030). Pgp expression was significantly lower in cancer tissue compared to normal mucosa (p < 0.001) and was related to grading, being lower in poorly-differentiated tumors (p < 0.05); however, no relationship was seen between Pgp expression, genotype and long-term prognosis.

CONCLUSION

G2677T and C3435T polymorphisms are not associated with colon cancer risk and prognosis in a selected patient population.