SET and MYND Domain-Containing Protein 3 (SMYD3) Polymorphism as a Risk Factor for Susceptibility and Poor Prognosis in Ovarian Cancer
Ting-Ting Liu, Hui Xu, Wei-Ping Gao, Shu-Xiang Zhang, Xu-Hong Zhou, Juan Tang, Qiong-Na Liu
Department of Obstetrics and Gynecology, The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, Jiangsu, China (mainland)
Med Sci Monit 2016; 22:5131-5140
We investigated the relationship of the polymorphisms of SET and MYND domain-containing protein 3 (SMYD3) with risk and prognosis of ovarian cancer.
MATERIAL AND METHODS: The polymerase chain reaction (PCR) amplification method was applied to detect the polymorphisms of variable number of tandem repeats (VNTR) in the SMYD3 gene promoter region for 156 patients with ovarian cancer (case group) and 174 healthy people (control group). Quantitative reverse transcription polymerase chain reaction and Western blot were applied to detect SMYD3 mRNA and protein expressions.
RESULTS: The frequencies of VNTR genotype 3/3 and allele genotype 3 in the case group were significantly higher than those in the control group, while the frequency of genotype 2/2 in the control group was significantly higher than that in case group (all P<0.05). The proportion of poorly differentiated patients carrying VNTR genotype 3/3 was significantly higher than the proportion of poorly differentiated patients carrying VNTR genotype 2/2+2/3, while the proportion of patients carrying genotype 3/3 with International Federation of Gynecology and Obstetrics (FIGO) stage III–IV disease was significantly higher than the proportion of patients carrying genotype 2/2 +2/3 with FIGO stage III–IV disease (all P<0.05). SMYD3 mRNA and protein expressions were higher in the patients carrying genotype 3/3 than they were in the patients with the 2/2+2/3 genotype (all P<0.05). The 5-year survival rate for patients carrying VNTR genotype 3/3 was significantly lower than that of patients carrying genotype 2/2+2/3, and Cox regression analysis showed that VNTR genotype 3/3 was an independent risk factor for ovarian cancer prognosis (all P<0.05).
CONCLUSIONS: VNTR genotype 3/3 of the SMYD3 gene was associated with the risk of ovarian cancer. The polymorphism of VNTR genotype could be recognized as an indicator for the poor prognosis of patients with ovarian cancer.
Keywords: Female, Base Sequence, Aged, Adult, Gene Frequency - genetics, Genetic Predisposition to Disease, Histone-Lysine N-Methyltransferase - genetics, Humans, Kaplan-Meier Estimate, Logistic Models, Middle Aged, Minisatellite Repeats - genetics, Multivariate Analysis, Ovarian Neoplasms - genetics, Prognosis, Proportional Hazards Models, RNA, Messenger - metabolism, Risk Assessment, Risk Factors, young adult