A MAP3k1 SNP predicts survival of gastric cancer in a Chinese population.
OBJECTIVE
Genome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis.


METHODS
We genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer.


RESULTS
Our findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P = 0.028 for AC versus AA/CC, hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.03-1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients.


CONCLUSIONS
In conclusion, we demonstrate that MAP3K1 rs889312 is closely correlated with outcome among diffuse-type gastric cancer. This raises the possibility for rs889312 polymorphisms to be used as an independent indicator for predicting the prognosis of diffuse-type gastric cancer within the Chinese population.
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Xiaowei
X
Wei
Central Laboratory, Shanxi People's Hospital, Xi'an, Shanxi Province, China.
Enke
E
Zhang
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Chun
C
Wang
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Dongying
D
Gu
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Lili
L
Shen
Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, China; Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Meilin
M
Wang
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Zhi
Z
Xu
Department of General Surgery, Yixing Tumor Hospital, Yixing, Jiangsu Province, China.
Weida
W
Gong
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Cuiju
C
Tang
Central Laboratory, Shanxi People's Hospital, Xi'an, Shanxi Province, China.
Jinglong
J
Gao
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Jinfei
J
Chen
Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, China; Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Zhengdong
Z
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002681:China; D005260:Female; D005743:Gastrectomy; D055106:Genome-Wide Association Study; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D016019:Survival Analysis
D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human