Roles of ABCB1 gene polymorphisms and haplotype in susceptibility to breast carcinoma risk and clinical outcomes.

Abstract

PURPOSE:

Genetic variants of ABCB1 gene contributed to cancer susceptibility and interindividual differences in chemotherapy response. Therefore, we investigated the relevance between genetic variations in ABCB1 gene and both risk and clinical outcomes of breast carcinoma.

METHODS:

A case-control study was performed on the SNPs C3435T, C1236T and G2677T/A in 1,173 Chinese breast carcinoma patients and 1,244 age- and sex-matched controls. These SNPs were typed by PCR-restriction fragment length polymorphism assays.

RESULTS:

We found the following: (1) ABCB1 C3435T, G2677T/A variants and haplotype 3435T-1236T-2677T significantly increased the risk of breast carcinoma [adjusted OR (95 % CI): 1.281 (1.021-1.285), 1.326 (1.182-1.487) and 1.707 (1.498-1.945), respectively]. (2) A significantly enhanced therapeutic response was observed in both C3435T variants and haplotype 3435T-1236T-2677T after neoadjuvant anthracycline-based chemotherapy (n = 148) [adjusted OR (95 % CI): 2.695 (1.172-6.211) and 8.064 (1.085-58.823), respectively]. (3) Cox proportional hazards regression models showed that the hazards ratio (HR) for progression-free survival (PFS) associated with C3435T CC genotype was 1.664 (95 % CI: 1.022-2.708, P = 0.041). Kaplan-Meier curve showed that C3435T CC carriers had a poor prognosis than those with CT/TT carriers after anthracycline-based chemotherapy (P = 0.043, n = 762). Furthermore, ABCB1 C3435T variants showed a significantly prolonged both PFS and overall survival (OS) in patients with triple-negative (ER-/PR-/HER2-) status (P = 0.001 and P = 0.016, respectively; n = 135). In addition, there was a significantly longer OS in patients with HER2-negative status who had G2677T/A variants (P = 0.036, n = 487). However, we did not find statistically significant association between C1236T genotypes and the risk or prognosis of breast carcinoma.

CONCLUSIONS:

These results suggest that ABCB1 gene C3435T, G2677T/A variations and haplotype 3435T-1236T-2677T relate to the risk and clinical outcomes of breast carcinoma and may function as candidate molecular markers of anthracycline chemosensitivity in breast carcinoma.

• Authors: Huizhe Wu, Hui Kang, Yong Liu, Weiwei Tong, Duo Liu, Xiuli Yang, Minqiong Lian, Weifan Yao, Haishan Zhao, Desheng Huang, Xianzheng Sha, Enhua Wang, Minjie Wei
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 9 Pg. 1449-62 (Sep 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22526155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Anthracyclines

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adult
• Aged
• Aged, 80 and over
• Anthracyclines (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease (genetics)
• Haplotypes
• Humans
• Lymphatic Metastasis
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Outcome Assessment, Health Care (statistics & numerical data)
• Polymorphism, Single Nucleotide
• Prognosis
• Proportional Hazards Models
• Risk Factors
• Survival Analysis
• Young Adult