A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

Daniele Campa; Phillip Müller; Lutz Edler; Lena Knoefel; Roberto Barale; Claus P Heussel; Michael Thomas; Federico Canzian; Angela Risch

doi:10.1002/ijc.27567

A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

Int J Cancer. 2012 Dec 15;131(12):2920-8. doi: 10.1002/ijc.27567. Epub 2012 Jul 3.

Authors

Daniele Campa¹, Phillip Müller, Lutz Edler, Lena Knoefel, Roberto Barale, Claus P Heussel, Michael Thomas, Federico Canzian, Angela Risch

Affiliation

¹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

PMID: 22473764
DOI: 10.1002/ijc.27567

Abstract

ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression-free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression-free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics*
Antineoplastic Agents / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Small Cell / drug therapy
Carcinoma, Small Cell / pathology
Female
Haplotypes
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / pathology
Male
Middle Aged
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins / genetics*
Neoplasm Proteins / genetics*
Polymorphism, Genetic*
Prognosis

Substances

ABCB1 protein, human
ABCC2 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Antineoplastic Agents
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
Neoplasm Proteins