The relationship of TNFAIP8 polymorphism with OC risk
In this case-control study, three SNPs (rs11064, rs1045241, and rs1045242) in TNFAIP8 gene were selected and analyzed. The genotype frequencies of each SNP conformed to the Hardy-Weinberg equilibrium among controls (P > 0.05 for all). Displayed in Table 2, TNFAIP8 rs11064 A-allele (COR: 0.690, 95%CI: 0.491–0.971, P = 0.033 and AOR: 0.709, 95%CI: 0.504–0.997, P = 0.048) and rs1045242 G-allele (COR: 1.619, 95%CI: 1.129–2.323, P = 0.009 and AOR: 1.628, 95%CI: 1.132–2.342, P = 0.009) are risk factors for OC. However, the allele of TNFAIP8 rs1045241 had no effect on the risk of OC (P > 0.05).
For further examination, we conducted the correlation between the genotypes of SNPs and OC risk by logistic regression analysis under the codominant, dominant, and recessive models (Table 3). Our results showed that rs11064 was significantly associated with increased OC susceptibility in codominant model (GG/AA, COR: 0.200, 95%CI: 0.057–0.706, P = 0.012 and AOR: 0.205, 95%CI: 0.058–0.726, P = 0.014) and recessive model (GG/AA + AG, COR: 0.209, 95%CI: 0.060–0.731, P = .014 and AOR: 0.212, 95%CI: 0.060–0.744, P = 0.016). Also, we demonstrated that rs1045242 was related to a higher risk of OC under codominant model (AG/AA, COR: 1.670, 95%CI: 1.091–2.558, P = 0.018 and AOR: 1.703, 95%CI: 1.108–2.618, P = 0.015) and dominant model (AG + GG/AA, COR: 1.736, 95%CI: 1.149–2.623, P = 0.009 and AOR: 1.761, 95%CI: 1.162–2.670, P = 0.008). However, there was no significant association between TNFAIP8 rs1045241 and OC risk.
Stratification analysis between TNFAIP8 SNPs and OC risk based on age, smoking history, complication, and family history
Aiming to deeply analyze the relationships of TNFAIP8 genotypes with OC susceptibility, we divided age into ≤ 54 years old and > 54 years old, whether smoking, whether complication (patients with diabetes and cardio-cerebrovascular disease), and whether there is family history of OC. It revealed that rs1045242 mutation (AG + GG/AA) would significantly increase risk of OC (OR: 2.048, 95%CI: 1.116–3.757, P = 0.021) at age ≤ 54 years old (Supplementary Table 1). In subjects with no smoking history, the rs11064 mutation (GG) was a protective factor for OC (OR: 0.164, 95%CI: 0.036–0.742, P = 0.019). On the contrary, the rs1045242 mutation (AG + GG) was a risk factor for OC (OR: 2.670, 95%CI: 1.141–6.247, P = 0.024) in subjects with smoking history (Supplementary Table 2). As showed in Supplementary Table 3 and Table 4, the rs1045242 mutation (AG + GG) was a risk factor for OC in subjects with no complication (OR: 1.829, 95%CI: 1.109–3.018, P = 0.018) and no family history of OC (OR: 1.746, 95%CI: 1.150–2.650, P = 0.009). The rs11064 GG genotype was a protective factor for OC in subjects with no family history of OC (OR: 0.205, 95%CI: 0.058–0.724, P = 0.014).