Is there a dose-dependent effect of genetic susceptibility loci for gastric cancer on prognosis of the patients?

Cheng, Lei

Qiu, Li-Xin

Jia, Ming

Zhou, Fei

Wang, Meng-Yun

Zhang, Ruo-Xin

Yang, Yajun

Wang, Xiaofeng

Wang, Jiucun

Jin, Li

Wei, Qing-Yi

2021-07-08T15:51:56Z

2021-07-08T15:51:56Z

2017-03

2021-07-08T15:51:55Z

Literature suggests that genetic variants associated with increased susceptibility to gastric cancer (GCa) are mostly located in genes involved in carcinogenesis and possibly tumor progression. Therefore, we hypothesize that high genetic susceptibility is also associated with prognosis of the patients. To test this hypothesis, we selected a total of 42 common genetic variants that were reportedly associated with GCa risk with a high level of evidence obtained from either genome-wide association studies (GWASs) or meta-analyses and performed survival analysis of patients used in a case-control analysis. We first used 1115 GCa cases and 1172 cancer-free controls of ethnic Han Chinese to construct a weighted genetic risk score (GRS). Then, we included 633 GCa cases with available clinical information, fit GRS in a fractional polynomial Cox proportional hazards regression model to investigate whether there is a dose-dependent effect of GRS on risk of death in survival analysis. Dynamic predictive value of genetic risk for prognosis was also calculated. The results showed that the increase of GRS had no effect on risk of death in these GCa patients. Compared with GCa patients with the medium GRS, there was no significant difference in survival in patients with either a low (P = 0.349) or a high (P = 0.847) GRS. The results unchanged when data were stratified by tumor stage and Lauren's classification. Time-dependent predictive value for prognosis in considering both clinical factors and GRS was comparable with that in considering clinical factors alone, for either all patients (P = 0.986) or stage- and Laruen type-based subgroups (P > 0.05 for all). In conclusion, higher polygenic susceptibility loci for GCa may not indicate worse prognosis of Chinese patients. Additional variants of relevant genes modulating GCa patients' survival need to be further identified.

13123

1949-2553

1949-2553

https://hdl.handle.net/10161/23439

eng

Impact Journals, LLC

Oncotarget

10.18632/oncotarget.13123

Humans

Stomach Neoplasms

Genetic Predisposition to Disease

Prognosis

Risk Factors

Case-Control Studies

Genetic Variation

Genome-Wide Association Study

Is there a dose-dependent effect of genetic susceptibility loci for gastric cancer on prognosis of the patients?

Journal article

Wei, Qing-Yi|0000-0002-3845-9445

18435

18443

11

School of Medicine

Duke Cancer Institute

Population Health Sciences

Duke Global Health Institute

Medicine, Medical Oncology

Duke

Institutes and Centers

Basic Science Departments

University Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Clinical Science Departments

Published

8