Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy.
Abstract
Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1)
are crucial mediators of the intestinal microenvironment and are involved in radiation-induced
acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1
were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively
evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed
the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities
after radiotherapy. Acute adverse events were scored, including dermatitis, fecal
incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The
patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute
toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and
PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate
the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%)
had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals
who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients
that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively.
The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated
with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes
of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The
CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity
compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1
genes were associated with acute injury in rectal cancer patients treated with pelvic
irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity
in patients with rectal cancer if validated in future studies.
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https://hdl.handle.net/10161/18029Published Version (Please cite this version)
10.2147/OTT.S83723Publication Info
Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; ...
Zhang, Zhen (2015). Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity
in Chinese rectal cancer patients treated with pelvic radiotherapy. OncoTargets and therapy, 8. pp. 2291-2301. 10.2147/OTT.S83723. Retrieved from https://hdl.handle.net/10161/18029.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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