Is there a dose-dependent effect of genetic susceptibility loci for gastric cancer on prognosis of the patients?
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.
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.
Lei
L
Cheng
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.
Li-Xin
LX
Qiu
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.
Ming
M
Jia
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.
Fei
F
Zhou
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.
Meng-Yun
MY
Wang
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.
Ruo-Xin
RX
Zhang
Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
Yajun
Y
Yang
Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
Xiaofeng
X
Wang
Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
Jiucun
J
Wang
Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
Li
L
Jin
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Xuhui, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Xuhui, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Qing-Yi
QY
Wei
D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D011379:Prognosis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics*
gastric cancer; genetic risk score; genome-wide association study; prognosis