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Diphenyl difluoroketone (EF-24), a synthetic curcumin analog, has enhanced bioavailability over curcumin. EF-24 acts more powerful bioactivity for anti-inflammatory and anti-cancer activity. However, the effects and mechanism of EF-24 on cervical cancer has not been fully investigated. Herein, this study evaluated the effects of EF-24 on TPA-induced cellular migration of cervical cancer. The results showed that EF-24 substantially reduced the cellular migration and cellular invasion of the HeLa and SiHa cells. Moreover, gelatin zymography, western blotting analyses and real-time PCR revealed that EF-24 suppressed Matrix metalloproteinase-9 (MMP-9) activity, protein expression and mRNA levels. Mechanistically, EF-24 inhibited the phosphorylation of the p38 signaling pathway. In conclusion, EF-24 inhibited TPA-induced cellular migration and cellular invasion of cervical cancer cell lines through modulating MMP-9 expression via downregulating signaling p38 pathway and EF-24 may have potential to serve as a chemopreventive agent of cervical cancer.

Endometriosis has been shown to increase the risk of gynecological cancers. However, the effect of gestrinone, a clinical endometriosis drug, on gynecological cancers remains unclear. This study aimed to understand the effect of gestrinone on gynecological cancers. A retrospective study was conducted using the Longitudinal Health Insurance Database 2000 of the Taiwan National Health Insurance Research Database (NHIRD) to observe the risk of gynecological cancers. Medication records from the Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital CSMUH and cancer records from the Taiwan Cancer Registry were collected to analyze the correlation between gestrinone use and gynecological cancers. Subsequently, human cell lines were used to investigate the effect of gestrinone on gynecological cancers. A total of 8330 endometriosis patients were enrolled, and analyses revealed that endometriosis patients had a higher risk of developing ovarian and endometrial cancer. However, the rate of cervical cancer was not statistically different (P = 0.249). Analyses of both the NHIRD and CSMUH databases revealed that gestrinone may reduce the risk of gynecological cancer. Cellular experiments verified the anticancer effects of gestrinone, which effectively and specifically inhibited the growth of HeLa cervical cancer cells, decreased P21 expression via JNK phosphorylation, and induced apoptosis. Combining the results of clinical database analysis and cell experiments, our findings prove that gestrinone has the potential to protect against cancer through regulation of the JNK-P21 axis. Repurposing the anticancer efficacy of gestrinone may be a strategy for targeted therapy in the future.

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.

The relationship between uterine corpus cancer and endometriosis was conflicting. We aimed to determine the risk of uterine cancer in patients with endometriosis or pelvic inflammatory disease (PID). In this population-based cohort study, a total of 135,236 females with endometriosis (n = 20,510) or PID (n = 114,726), as well as 135,236 age-matched controls, were included. Cox regression models estimated the risk of uterine cancer in each group. Sub-outcomes of risk for uterine corpus cancer included endometrial cancer and uterine sarcoma were analyzed. An age subgroup analysis was performed to determine the moderator effect of age. A landmark analysis depicted the time varying effect of endometriosis and PID. A propensity score matching analysis was conducted to validate the findings. Patients with endometriosis had significantly higher risk of endometrial cancer (adjusted hazard ratio, aHR = 2.92; 95% CI = 2.12–4.03) and uterine sarcoma (aHR = 5.83; 95% CI = 2.02–16.89), while PID was not associated with the risk of uterine cancer. The increased risk of uterine cancer in patients with endometriosis persisted after propensity score matching (aHR = 2.83, 95%CI = 1.70–4.71). The greatest risk of endometrial cancer occurred in patients who had endometriosis for 37 to 60 months (adjusted relative risk, aRR = 9.15, 95% CI = 4.40–19.02). Females aged 12 to 35 years were at the greatest risk of endometriosis-associated uterine cancer (RR = 6.97, 95% CI = 3.41–14.26). In conclusion, patients with endometriosis were at great risk of uterine cancer, including endometrial cancer and uterine sarcoma, compared with propensity score-matched populations and compared with patients of PID. Younger females with endometriosis and patients who had endometriosis for three to five years were at the greatest risk of endometriosis-associated uterine cancer.

The aims of this study were to explore the involvement of Aurora kinase A (AURKA) gene single nucleotide polymorphisms (SNPs) in uterine cervical cancer that has not yet been investigated. One hundred and six patients with cervical invasive cancer and 94 patients with precancerous lesions, and 302 Taiwanese female individuals were included. AURKA SNPs rs2273535, rs6024836, rs2064863 and rs1047972 were analyzed for genotypic distributions using real-time polymerase chain reaction. There were no statistically significant differences in the genetic frequencies of AURKA SNPs among patients with invasive cancer and those with precancerous lesions of uterine cervix and control women. There were no associations among AURKA SNPs and clinicopathologcal variables and recurrence and survival events. However, in a multivariate analysis, cervical cancer patients with adenocarcinoma (HR: 3.18, 95% CI: 1.23-8.23; p=0.017) and larger tumor (HR: 5.61, 95% CI: 2.10-14.95; p=0.001) had poorer recurrence-free survival. In conclusion, tumor size and pelvic lymph node status rather than AURKA SNPs were the most obvious independent parameter that could significantly predict 5 years survival rate in Taiwanese women with cervical cancer.

Dioscorea nipponica Makino has been used for the treatment of chronic bronchitis, rheumatoid arthritis, cough, and asthma. Several studies have established the antitumor effect of D. nipponica Makino extract (DNE). However, no investigations have considered the antimetastatic potential of DNE in cervical cancer cells. The present study examined the effects of DNE on cervical cancer cells treated with 12-O-tetradecanoylphorbol-13-acetate and characterized the possible molecular mechanisms. MTT assay results indicated that DNE exhibited very low cytotoxicity, and DNE significantly reduced the invasion and migration abilities of cervical cancer cells. Gelatin zymography analysis revealed that DNE significantly inhibited matrix metalloproteinase-9 (MMP-9) activity. Reverse transcription-polymerase chain reaction assay results revealed that DNE treatment inhibited the MMP-9 mRNA levels of HeLa and SiHa cells. Western blot results revealed that DNE significantly diminished the ERK1/2 phosphorylation. In conclusion, we revealed that the antimetastatic effects of DNE on cervical cancer cells are due to its inhibition of MMP-9 expression through the ERK1/2 pathway.

The purposes of the investigation were to examine the implications of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in progression and clinicopathological factors of uterine cervical cancer, and patient survival in Taiwan. Genotypic distributions of two GAS5 genetic variants rs145204276 and rs55829688 were detected in 208 patients including 111 patients with invasive cancer, 97 with precancerous lesions as well as 307 control women using real-time polymerase chain reaction. It explored that patients with cervical precancerous lesion had lower rate of AGGCA deletion (Del) in both alleles (Del/Del) of GAS5 rs145204276 as compared with control women. Patients with invasive cancer did not exhibit higher rate of Del/Del. Meanwhile, there were no different genotypic distributions in rs55829688 among patients with cervical invasive cancer and those with precancerous lesions as well as control women. Moreover, cervical cancer patients with Ins (insertion, AGGCA)/Del and Del/Del (-/-) in GAS5 rs55829688 tended to have poorer hazard ratio (HR) of 5 years survival. In addition, lymph node metastasis status exerted the most significantly predictive of 5 years survival rate. Conclusively, GAS5 polymorphism rs145204276 is probably applicable to predict 5 years survival HR of cervical cancer patients. However, the mechanism elucidating the methylation status and transcription function of rs145204276 in uterine cervical cancer needs to be delineated for its unique implication in uterine cervical cancer.

Objective to compare the urine protein-to-creatinine ratios (uPCRs) during labor at term between normal and women with pregnancy-induced hypertension (PIH), and to evaluate the patterns of change in uPCRs. Design observational study Setting Tertiary referral hospital in Taiwan Population normal pregnant or women only with PIH at term were enrolled Methods and Main outcome measures uPCRs in four phases (latent, active, recovery and early postpartum) and related clinical data at delivery were collected. Multivariate analysis with a linear regression model were performed to analyze continuous variables after adjusting for clinical data between two groups. Results 68 normal and 24 pregnant women with PIH were included. There were no differences in the uPCR or the proportion cases of uPCRs ≥ 300 mg/g between normal and PIH group in the latent, active, recovery or early postpartum phases. There was a statistically significant tendency for the proportion of uPCRs ≥ 300 mg/g to increase from the latent to the early postpartum phase in both groups. The proportion of uPCRs ≥ 300 mg/g significantly increased from the active to the recovery phase and then declined from the recovery to the early postpartum phase in normal pregnant women.Thus no differences in uPCRs cases change between any two phases in women with PIH, except the duration above stated. Conclusion. This is the first study to demonstrate that uPCRs data are not different between normal pregnant and PIH groups during the course of labor, but it did show different dynamic change patterns throughout the labor phases.

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (

The objectives of this study were to define the associations among single nucleotide polymorphisms (SNPs) of metastasis-associated in colon cancer-1 (MACC1) gene, development and clinicopathological characteristics of uterine cervical cancer, and patient survival in Taiwan. Genotypic frequencies of 5 MACC1 SNPs rs975263, rs3095007, rs4721888, rs3735615 and rs1990172 were identified for 132 patients with invasive cancer, 99 with high-grade cervical intraepithelial neoplasia and 338 normal controls using real-time polymerase chain reaction. It revealed that there were no associations of these MACC1 SNPs with cervical carcinogenesis. In the meantime, cervical cancer patients with genotype GG in MACC1 SNP rs975263 tended to display more risk to have vaginal invasion than those with AA/AG (p=0.042, OR: 8.70, 95% CI: 0.81-433.22). In multivariate analysis, positive pelvic lymph node metastasis could significantly predict worse 5 years survival rate (p=0.001; HR=9.98, 95% CI=2.64-37.77) for cervical cancer patients. In conclusion, pelvic lymph node status rather than MACC1 SNPs was the only independent parameter that could significantly predict 5 years survival rate in Taiwanese women with cervical cancer.

Cyclosporin A is an immunosuppressive drug with anti-cancer effect. Arsenic trioxide (As

To compare the rate and risk of ovarian cancer in patients with endometriosis or pelvic inflammatory disease (PID). A nationwide population cohort research compared the risk of ovarian cancer in 135,236 age-matched comparison females, 114,726 PID patients, and 20,510 endometriosis patients out of 982,495 females between 1 January 2002 and 31 December 2014 and ended on the date of confirmation of ovarian cancer, death, or 31 December 2014. In order to reduce the unbalanced characteristics, propensity score matching (PSM) was performed for 20,478 females in each subgroup. The incidence rate (per 100,000 person–years) of ovarian cancer was 8.74 (95% CI, 7.16–10.66) in comparison, 9.26 (7.54–11.39) in PID, and 28.73 (21.07–39.16) in endometriosis cohorts. The adjusted hazard ratio (aHR) of ovarian cancer was 1.17 (p = 0.296) in PID and 3.12 (p &lt, 0.001) in endometriosis cohorts, compared with the comparison cohort in full cohort, using the multiple Cox regression model. The aHR of ovarian cancer was 0.83 (p = 0.650) in PID and 3.03 (p = 0.001) in endometriosis cohorts, compared with the comparison cohort after performing PSM. In the full cohort and PSM population, the cumulative incidence rate of ovarian cancer was significantly higher in patients with endometriosis than in those with PID or in the comparison cohort (p &lt, 0.001 and p &lt, 0.001). In conclusion, after considering the differences in the impacts of exposure to endometriosis or PID, patients with endometriosis were more likely to develop ovarian cancer.

Simple Summary The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. Metformin exerts anticancer effects, alone or in combination with other agents, on cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Abstract Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

Simple Summary Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy. Abstract Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIXhigh/PFKFB4high expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.

Endometrial cancer (EC) is the second most common gynecological malignancy worldwide. Tribbles pseudokinase 3 (TRIB3) is a scaffolding protein that regulates intracellular signal transduction, and its role in tumor development is controversial. Here, we investigated the biological function of TRIB3 in EC. We found that the messenger RNA (mRNA) expression level of TRIB3 was significantly and positively correlated with shorter overall survival of EC patients in The Cancer Genome Atlas database. The protein expression of TRIB3 was found to be significantly increased in EC cancer stem cells (CSCs) enriched by tumorsphere cultivation. Knockdown of TRIB3 in EC cells suppressed tumorsphere formation, the expression of cancer stemness genes, and the in vivo tumorigenesis. The expression of &beta, catenin at both the protein and the mRNA levels was downregulated upon TRIB3 silencing. TRIB3 was found to interact with E74 Like ETS transcription factor 4 (ELF4) in the nucleus and bound to ELF4 consensus sites within the catenin beta 1 (CTNNB1) promoter in EC cell lines. These data indicated that TRIB3 may regulate CTNNB1 transcription by enhancing the recruitment of ELF4 to the CTNNB1 promoter. In conclusion, our results suggest that TRIB3 plays an oncogenic role in EC and positively regulates the self-renewal and tumorigenicity of EC-CSCs. Targeting TRIB3 is considered as a potential therapeutic strategy in future EC therapy.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC.

It has been reported that oxidative and nitrative stress might be the pathogenesis of endometriosis. This prospective case-control study attempted to check the connection between single nucleotide polymorphism (SNP) of three antioxidant enzymes (glutathione peroxidase 4 (GPX4), thioredoxin 2 (TXN2), thioredoxin reductase 1 (TXNRD1)) and endometriosis. We recruited 90 patients with histology-approved endometriosis as the case group and 130 age-matched women for an annual pap smear examination as the control group. The stage of endometriosis was evaluated with revised ASRM score. Both groups were genotyped in the peripheral leukocytes for the SNP of GPX4 (rs713041), TXN2 (rs4821494) and TXNRD1 (rs1128446) by PCR-based methods. An X2 test was used to analysis of the difference of allele frequency and SNP distribution between two groups. The results revealed GPX4 (rs713041) has a significantly different distribution between two groups (C:T = 116 (44.6%):144 (55.4%) in control and C:T = 104 (57.8%): 76 (42.2%) in endometriosis groups, p = 0.007). The SNP in TXN2 (rs4821494) also showed a difference in allele frequency (G:T = 180 (69.2%):80 (30.8%) in control and G:T = 141 (78.3%):39 (21.6%) in endometriosis group, p = 0.030). In addition, the SNP GPX4 (rs713041) was associated with the severity of the endometriosis. Women who have advanced stage endometriosis were different from mild endometriosis in genetic variants of GPX4 gene (p = 0.001). In conclusion, the relationship between endometriosis and SNP of antioxidant enzymes, GPX4 and TXN2, was confirmed by the present study. According to the result, we suggested that the GPX4 might contribute to the pathogenesis of endometriosis.

It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08–1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86–1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16–4.44] and 2.00 [95% CI, 1.13–3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.

The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.

To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.

To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.