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Genetic polymorphisms and gene-dosage effect in ovarian cancer risk and response to paclitaxel/cisplatin chemotherapy

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, January 2015
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Title
Genetic polymorphisms and gene-dosage effect in ovarian cancer risk and response to paclitaxel/cisplatin chemotherapy
Published in
Journal of Experimental & Clinical Cancer Research, January 2015
DOI 10.1186/s13046-015-0124-y
Pubmed ID
Authors

Karolina Tecza, Jolanta Pamula-Pilat, Zofia Kolosza, Natalia Radlak, Ewa Grzybowska

Abstract

BackgroundOvarian malignancies are often diagnosed in advanced stage and at the same time resistance to treatment, both intrinsic and developed during treatment, is sometimes observed. These facts underscore the need for new markers of ovarian cancer risk, as well as markers of treatment effectiveness.MethodsIn this study we genotyped 225 ovarian cancer patients, 64 breast and ovarian cancer patients and 348 healthy controls. In total, 12 polymorphic variants and 2 deletions in PGR, ABCB1, ABCG2, GSTT1, GSTM1, GSTP1, ATM, TP53 and ATP7B genes were analyzed using ASA-PCR, RFLP-PCR, multiplex-PCR and sequencing.ResultsTen genetic polymorphisms were significantly associated with the risk of developing ovarian carcinoma in at least one of the groups under study. Impact of PGR gene polymorphisms on ovarian cancer risk was specific only for the group of the BRCA1 mutation carriers (in presence of p.Val660Leu variant- OR 2,82; p¿=¿0,010), which confirms the difference in modulation of ovarian cancer risk between sporadic and hereditary malignancies, including the breast-ovarian cancer group (as a cancer-prone group). The analyses showed also the importance of ATP7B gene in ovarian carcinogenesis, both studied variants of which significantly modulated the ovarian cancer risk in all groups excluding the group with BRCA1 mutation. Cumulative risk analysis revealed 3 unfavorable variants that increased significantly the risk of developing ovarian cancer (p.Ile1145¿=¿ABCB1+ p.Asp1853Asn ATM+ p.Ser406Ala ATP7B- OR 7,47; p¿=¿0,002) and significantly modified the progression free survival (PFS) of the patients, and also two favorable genotypes which protected against ovarian cancer (p.Arg952Lys ATP7B+ p.Arg72Pro TP53- OR 0,50; p¿=¿0,008). PFS analysis for carriers of favorable versus unfavorable genotypes emphasized the impact of the regulation of cell cycle (p.Asp1853Asn ATM) and active transport of xenobiotics (p.Ser894Ala/Thr ABCB1) on the risk of disease progression (HR 3,81; p¿=¿0,010) after paclitaxel/cisplatin chemotherapy.ConclusionsThe unfavorable genetic variants could facilitate carcinogenic process and once their carriers developed malignancy, their chances of survival were smaller. Our analyses also showed a strong gene-dosage effect with the decrease of progression-free survival for the carriers of two unfavorable genetic factors.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 18%
Student > Bachelor 5 18%
Researcher 4 14%
Student > Doctoral Student 2 7%
Student > Ph. D. Student 2 7%
Other 4 14%
Unknown 6 21%
Readers by discipline Count As %
Medicine and Dentistry 7 25%
Biochemistry, Genetics and Molecular Biology 7 25%
Agricultural and Biological Sciences 4 14%
Psychology 1 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Other 0 0%
Unknown 8 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 January 2015.
All research outputs
#22,758,309
of 25,373,627 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#1,967
of 2,378 outputs
Outputs of similar age
#307,792
of 360,070 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#19
of 28 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,378 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 360,070 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.