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Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

ABSTRACT: Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from the ABCC1, ABCC2, ABCB1, and ABCG2 genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only the ABCB1 SNPs showed a significant association with BC in Jordanian-Arab patients, and the ABCB1 SNP rs2032582 exhibited a strong genotypic association with BC. With regard to the clinical characteristics of BC, the ABCC2 SNPs rs2273697 and rs717620 were found to be significantly associated with age at breast cancer diagnosis and breastfeeding status, while the ABCB1 SNP rs1045642 was significantly associated with age at breast cancer diagnosis. In terms of pathological characteristics, the ABCC1 SNP rs35628 and the ABCB1 SNP rs2032582 were significantly associated with tumor size, the ABCC2 SNP rs2273697 was significantly associated with estrogen receptor status, and the ABCG2 SNP rs2231142 was significantly associated with axillary lymph node status. In this current study, we assume that significant genetic variants within the ABC superfamily may increase the risk of breast cancer among Jordanian women. Furthermore, these variants might be responsible for worse BC prognosis.

SUBMITTER: Al-Eitan LN

PROVIDER: S-EPMC6662487 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

Al-Eitan Laith N LN Rababa'h Doaa M DM Alghamdi Mansour A MA Khasawneh Rame H RH

Journal of oncology 20190717

Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from the ABCC1, ABCC2, ABCB1, and ABCG2 genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only the ...[more]

PMID: 31391850

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Project description:Plants are master regulators of rhizosphere ecology, secreting a complex mixture of compounds into the soil, collectively termed plant root exudate. Root exudate composition is highly dynamic and functional, mediating economically important interactions between plants and a wide range of soil organisms. Currently we know very little about the molecular basis of root exudate composition, which is a key hurdle to functional exploitation of root exudates for crop improvement. Root expressed transporters modulate exudate composition and could be manipulated to develop beneficial plant root exudate traits. Using Virus Induced Gene silencing (VIGS), we demonstrate that knockdown of two root-expressed ABC transporter genes in tomato cv. Moneymaker, ABC-C6 and ABC-G33, alters the composition of semi-volatile compounds in collected root exudates. Root exudate chemotaxis assays demonstrate that knockdown of each transporter gene triggers the repulsion of economically relevant Meloidogyne and Globodera spp. plant parasitic nematodes, which are attracted to control treatment root exudates. Knockdown of ABC-C6 inhibits egg hatching of Meloidogyne and Globodera spp., relative to controls. Knockdown of ABC-G33 has no impact on egg hatching of Meloidogyne spp. but has a substantial inhibitory impact on egg hatching of G. pallida. ABC-C6 knockdown has no impact on the attraction of the plant pathogen Agrobacterium tumefaciens, or the plant growth promoting Bacillus subtilis, relative to controls. Silencing ABC-G33 induces a statistically significant reduction in attraction of B. subtilis, with no impact on attraction of A. tumefaciens. By inoculating selected differentially exuded compounds into control root exudates, we demonstrate that hexadecaonic acid and pentadecane are biologically relevant parasite repellents. ABC-C6 represents a promising target for breeding or biotechnology intervention strategies as gene knockdown leads to the repulsion of economically important plant parasites and retains attraction of the beneficial rhizobacterium B. subtilis. This study exposes the link between ABC transporters, root exudate composition, and ex planta interactions with agriculturally and economically relevant rhizosphere organisms, paving the way for new approaches to rhizosphere engineering and crop protection.

Dataset Information

Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

Publications

Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

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