Genetic polymorphisms and haplotypes of BRCA1 gene associated with quality of life and survival among patients with non-
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Genetic polymorphisms and haplotypes of BRCA1 gene associated with quality of life and survival among patients with non‑small‑cell lung cancer Tong Su1,2 · Hao Sun3 · Xiaofang Lu4 · Chen He1 · Lei Xiao1 · Jingwen He1 · Yang Yang5 · Yunxiang Tang1,2 Accepted: 16 April 2020 © Springer Nature Switzerland AG 2020
Abstract Purpose Quality of life (QoL) and prognosis of lung cancer (LC) patients are poor. Previous studies focused less on the relationship between genetic factors and the QoL of LC patients. The current study is intended to explore the association of SNPs and haplotypes of BRCA1 and the QoL and survival of patients with LC. Methods QOL of 291 non-small-cell LC patients was measured by EORTC Core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire‐Lung Cancer 13 (QLQ-LC13) before discharge. Three tag SNPs of the BRCA1 gene (rs1799966, rs3737559, rs8067269) were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The patients’ survival was followed up every six months until March 2019. Results rs8067269 was associated with physical functioning (β = 7.97, p = 0.024) and diarrhea (Odds ratios (OR) 0.32, p = 0.042). rs1799966–rs3737559–rs8067269 haplotype was associated with several domains of QoL, including physical functioning (TCG vs. CCA: β = 6.21, p = 0.010), worse dyspnea (TCG vs. CTA: OR 2.05, p = 0.031) and peripheral neuropathy (TCG vs. CTA: OR 3.91, p = 0.030). BRCA1 rs1799966 CC genotype, rs8067269 AA genotype and CCA haplotype were associated with longer survival time of LC patients (p 0.8 and MAF > 0.10. The genomic DNA was extracted using a Wizard Genomic DNA Purification Kit (Promega, Madison, Wisconsin, USA) as per the product instruction. The SNP genotyping work was performed using an improved multiplex ligation detection reaction (iMLDR) technique [34], with technical support from Genesky Biotechnologies Inc. (Shanghai, China). Negative controls and duplicate tests were designed. A random sample accounting for approximately 5% of the total DNA samples was directly sequenced using Big Dye-terminator version 3.1 and an ABI3730XL automated sequencer (Applied Biosystems) to confirm the results of iMLDR.
analyzed using the software Haploview v4.2 [35]. The association analysis between single polymorphism or haplotype and QoL was performed using the statistical program Plink v2.0 [36]. Linear regressions were performed for the continuous variables (Global health status/QoL and functional domains), and logistic regressions were performed for the dichotomized variables (symptom domains), while controlling for demographic and clinical characteristics. Statistical significance was corrected with Bonferroni methods. The principal model of association analysis was an additive model, using major alleles or major haplotype as reference. Kaplan–Meier method (Log-rank test) and Cox proportional hazard model were used to investigate potential influencing factors of survival time.
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