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Background  The ATP-binding cassette transporter B1 ( ABCB1 ) gene codes for a membrane efflux pump localized in epithelial cells. Together with other Permeability-glycoproteins in the small and large intestine, its product represents a barrier against xenobiotics, bacterial toxins, drugs and other substances introduced with diet, including carcinogens. The aim of this investigation was to verify the possible contribution of  ABCB1  single nucleotide polymorphisms (SNPs) to the genetic risk of colorectal cancer (CRC).    Results  DNA obtained from the peripheral blood of 98 CRC patients and 100 healthy controls was genotyped for the three selected SNPs: 1236C > T (rs1128503), 2677G > T/A (rs2032582), and 3435C > T (rs1045642). Molecular data were analyzed to asses allele and haplotype association with CRC.  No evidence of an association between  ABCB1  alleles and CRC occurrence as a whole was found. However,  ABCB1  showed either association with carcinoma of the sigmoid colon, and appeared able to influence the sex ratio among CRC patients. These two effects seemed to act independently based on multivariate analysis. We showed that  ABCB1  polymorphisms were able to influence CRC susceptibility related to tumor localization and patient gender.    Conclusions  We suggest that sensitivity to undetermined risk factors could depend on the genetic background of  ABCB1  locus, with a mechanism that also depends on patient gender.    Electronic supplementary material  The online version of this article (doi:10.1186/s12929-014-0089-8) contains supplementary material, which is available to authorized users.

Colorectal cancer susceptibility: apparent gender-related modulation by ABCB1 gene polymorphisms