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血型、ABO基因变异与卵巢癌生存率

Blood type, ABO genetic variants, and ovarian cancer survival.

作者信息

Cozzi Gabriella D, Levinson Rebecca T, Toole Hilary, Snyder Malcolm-Robert, Deng Angie, Crispens Marta A, Khabele Dineo, Beeghly-Fadiel Alicia

机构信息

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville TN, United States of America.

Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville TN, United States of America.

出版信息

PLoS One. 2017 Apr 27;12(4):e0175119. doi: 10.1371/journal.pone.0175119. eCollection 2017.

Abstract

OBJECTIVE

Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited.

METHODS

We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis.

RESULTS

ABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60-0.93) or all non-A (HR: 0.77, 95% CI: 0.63-0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25-0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39-0.99) in unadjusted models.

CONCLUSIONS

Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.

摘要

目的

A型血和A1等位基因与卵巢癌风险增加有关。迄今为止,仅有两项小型研究发表,ABO血型与卵巢癌生存率之间存在关联的证据有限。

方法

我们对范德比尔特大学医学中心肿瘤登记处确诊的卵巢癌病例进行了一项回顾性队列研究,这些病例的血型来自相关实验室报告,ABO变异来自相关的Illumina外显子芯片数据。通过比例风险回归模型的风险比(HR)和置信区间(CI)对与总生存期(OS)的关联进行量化;协变量包括年龄、种族、分期、分级、组织学亚型和诊断年份。

结果

713例主要为白种人(89.3%)的病例可获得ABO表型(N = 694)和/或基因型(N = 154)数据。在多变量模型中,与O型血(HR:0.75,95%CI:0.60 - 0.93)或所有非A型血(HR:0.77,95%CI:0.63 - 0.94)病例相比,A型血的总生存期显著更长。同样,错义rs1053878次要等位基因携带者(A2)的总生存期更好(HR:0.50,95%CI:0.25 - 0.99)。在白种人中,这种表型关联得到加强,但基因型关联减弱;相反,在未调整模型中,与O型变异具有中等连锁不平衡的四个变异与更好的总生存期相关(HR:0.62,95%CI:0.39 - 0.99)。

结论

在迄今为止最大规模的此类研究中,A型血与卵巢癌更长的生存期显著相关。这一发现得到了基因分析的支持,基因分析表明是A2等位基因,尽管与O相关的变异也有提示性关联。有必要对ABO与卵巢癌生存期进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/359b/5407760/d87092bf63e7/pone.0175119.g001.jpg

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