Characteristics of 840 subjects were summarized in Table 2. A total of 342 cervical cancer patients and 498 healthy controls were enrolled with mean ages of 43.27 ± 11.78 and 43.46 ± 13.03 years, respectively. There was no significant differences in age distribution between cases and controls. According the 2009 FIGO staging system, we divided 342 cervical cancer cases into different clinical stages, 132 cases (39%) were in stage I and II, 80 cases (23%) were in stage III and IV.
Detail information of RIPK1 polymorphisms, including chromosome, position, allele, genotype and allele distribution, MAF and HWE p value were listed in Table 3. The distribution frequencies of four SNPs were in HWE (p > 0.05). HaploReg showed that RIPK1 polymorphisms were related to the regulations of Enhancer histone marks, Motifs changed, and Selected eQTL hits. The relationship between RIPK1 polymorphisms and cervical cancer risk was shown in Table 4. Compared with the healthy controls, the individuals who carried with CC genotype of rs2077681 had higher risk of cervical cancer (codominant: OR = 3.14, 95% CI = 1.40-7.07, p = 0.006; recessive: OR = 3.20, 95% CI = 1.43-7.16, p = 0.005). FDR analysis verified the reliability of these results (codominant: FDR-p = 0.018; recessive: FDR-p = 0.018). There were no significant associations between other SNPs and cervical cancer risk in this study (p > 0.05).
We then performed stratification analysis on the association of RIPK1 polymorphisms with cervical cancer susceptibility (Table 5). In the subgroup of age > 43 years, individuals carrying the genotype CC in rs2077681 (codominant: OR = 3.38, 95% CI = 1.15-9.99, p = 0.027; recessive: OR = 3.46, 95% CI = 1.18-10.15, p = 0.024) and TT in rs17548629 (codominant: OR = 3.99, 95% CI = 1.04-15.32, p = 0.044; recessive: OR = 4.09, 95% CI = 1.07-15.63, p = 0.040) were more likely to suffer from cervical cancer, whereas FDR analysis showed the strong linkages of rs2077681 and rs17548629 with cervical cancer may not be reliable (FDR- p > 0.05). Moreover, we found that rs6907943 and rs17548629 exerted protective roles in higher grade cervical cancer among Uyghur population (rs6907943, allele: OR = 0.47, 95% CI = 0.24-0.90, p = 0.021; dominant: OR = 0.46, 95% CI = 0.23-0.93, p = 0.031; log-additive: OR = 0.46, 95% CI = 0.23-0.89, p = 0.022; rs17548629, allele: OR = 0.41, 95% CI = 0.21-0.83, p = 0.011; dominant: OR = 0.44, 95% CI = 0.21-0.93, p = 0.031; log-additive: OR = 0.43, 95% CI = 0.22-0.87, p = 0.018). However, allele (OR = 3.42, 95% CI = 1.55-7.56, p = 0.001), dominant (OR = 3.57, 95% CI = 1.55-8.22, p = 0.003) and log-additive (OR = 3.53, 95% CI = 1.56-7.98, p = 0.002) models revealed the remarkable associations of rs9503400 and increased risk of stage III/IV cervical cancer. Haplotype analysis did not show blocks in RIPK1 polymorphisms (Supplemental Figure 1), and no associations with risk of cervical cancer.