Review ArticleReview
Open Access

Inflammatory Cytokine Genotypic Markers and Ovarian Cancer Risk

WEN-SHIN CHANG, CHIA-WEN TSAI, JAW-CHYUN CHEN, YUN-CHI WANG and DA-TIAN BAU
Anticancer Research May 2026, 46 (5) 2863-2876; DOI: https://doi.org/10.21873/anticanres.18165

Abstract

Ovarian cancer is the most lethal gynecological malignancy worldwide, largely due to late diagnosis and lack of effective population-level screening tools. Inflammatory cytokines regulate proliferation, apoptosis, angiogenesis, and immune surveillance, making inherited variation in cytokine pathways biologically plausible determinants of ovarian cancer susceptibility and progression. Since the early 2000s, numerous candidate-gene studies have evaluated polymorphisms of genes such as the interleukin (IL) families, tumor necrosis factor alpha (TNFA), transforming growth factor beta 1 (TGFB1), and components of the nuclear factor kappa B (NFKB) signaling pathway and adhesion pathways, across diverse populations. In this review, we summarize these potential markers to give readers an overview showing accumulated evidence supports a coherent model in which genetically modulated inflammation is an integral driver of epithelial ovarian carcinogenesis. Collectively, studies reveal recurrent patterns of risk-increasing and risk-protective variants. Risky genotypes predicted to enhance pro-inflammatory, pro-angiogenic, or immunosuppressive signaling include IL1B rs16944 CC, IL6 rs1800795, IL8 rs2227306 TT, IL8 rs1126647 TT, IL16 rs11556218 GT/GG, IL16 rs4778889 CT/CC, IL23R rs10889677 AC/CC, IL31 rs4758680 CA/AA, IL32 rs28372698 TT, TNFA rs1800629 GA/AA, and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282 CG genotypes. Conversely, protective variants tend to dampen inflammatory tone or rebalance cytokine networks, including IL1A rs17561 GT/TT, IL1A rs4848300 CT/CC, IL1A rs3783553 insertion/insertion, IL1B rs7596684 CT/CC, IL6 rs1880242 GT/TT, IL31 rs7977932 CG/GG, TGFB1 rs1800469 CT/TT, selectin E (SELE) rs5361 AC, intercellular adhesion molecule 1 (ICAM1) rs5498 AG genotypes and specific IL6 haplotypes. Beyond risk per se, several polymorphisms appear predictive of clinical features, including tumor stage, cytoreductive resectability and recurrence, highlighting potential prognostic relevance. Notably, associations are often population-specific, reflecting differences in allelic frequencies and linkage disequilibrium across ethnic groups, underscoring the need for cross-ethnic replication. Further investigations may ultimately enable further improved the prevention, early detection, and personalized management of ovarian cancer.

Keywords:

Introduction

Ovarian cancer is the most lethal among all gynecological malignancies in women worldwide (1, 2), and affects 1.1-1.5% of women during their lifespan (3, 4). Its poor prognosis is largely driven by late diagnosis and the lack of effective population-level screening tools and practical markers (5-7). While high-penetrance mutations in breast cancer 1 DNA repair-associated (BRCA1) and breast cancer 2 DNA repair-associated (BRCA2) and mismatch-repair genes account for a subset of familial cases, most ovarian cancer arises sporadically and is thought to reflect the combined effects of environmental exposures and multiple low-penetrance genetic variants (8, 9).

Chronic inflammation is a central conceptual framework in ovarian carcinogenesis (10-12). Repeated ovulation, pelvic inflammatory disease, endometriosis and other pro-inflammatory conditions have been linked to increased ovarian cancer risk (13-16), whereas events that suppress ovulation and inflammation, such as parity and oral contraceptive use, reduce risk (17-20). Inflammatory cytokines regulate cell proliferation, apoptosis, angiogenesis, immune surveillance and stromal–tumor interactions, making them attractive candidates as indicating susceptibility to ovarian cancer (21, 22).

Since 2008, a series of candidate-gene epidemiological studies have evaluated polymorphisms in cytokine and cytokine receptor genes, including interleukin-1 (IL1) family genes (IL1A and IL1B), IL6, IL8, IL18, IL31, IL32, the interleukin 23 receptor gene (IL23R), tumor necrosis factor alpha (TNFA), transforming growth factor beta 1 (TGFB1), and components of nuclear factor kappa B (NFKB) pathway, in relation to ovarian cancer risk and clinical outcome across diverse populations (23-39). Here, we integrate the findings from such studies to provide a cohesive overview of how inherited variation in inflammatory pathways may contribute to ovarian carcinogenesis.

IL1 Axis Polymorphisms and Ovarian Cancer

As early as 2002, Hefler and colleagues started to investigated the influence of IL1A −889 (rs1800587), IL1B −511 (rs16944), IL1B exon 5 (rs114534), and an 86-bp variable number tandem repeat polymorphism in intron 2 of IL1RN (rs2234663) on ovarian cancer risk in an Austrian cohort (23). However, in their pilot analysis of allelic frequency only, they did not find any significant association (23). In 2004, Bushley and colleagues analyzed the contributions of IL1A −889 (rs1800587), +4845 (rs17561) and IL1B −3957 (rs1143634) in an American case–control cohort including 182 ovarian cancer cases and 219 controls (24). They found a significantly reduced risk of ovarian cancer risk among women with IL1A rs17561 GT/TT genotypes compared to women with wild-type GG genotype [odds ratio (OR)=0.59, 95% confidence interval (95% CI)=0.37-0.97, p=0.0143] after adjustment for age and ethnicity (24). However, the trend analysis showed no significance (p=0.100), suggesting this particular genotype cannot serve as a good predictive marker. In 2007, Braicu and colleagues evaluated the contributions of IL1A −889 (rs1800587) and IL1B −3957 (rs1143634) to ovarian cancer among 129 non-cancer control and 147 ovarian cancer cases in Germany (25). They found no significant association of either genotype with ovarian cancer, consistent with Bushley et al.’s work. In 2012, White and colleagues conducted a genome-wide analysis investigating the contributions of inherited inflammation-related genotypes to ovarian cancer in 3,972 epithelial ovarian cancer cases and 3,043 non-cancer controls from multiple sites, mainly located in the USA or UK (26). They evaluated the effects of IL1A rs17561, rs4848300, rs3783516, rs2856838, and IL1B rs7596684 genotypes on ovarian cancer risk. They found that IL1A rs17561, associated with a missense alteration of A to S in a 114 amino acid sequence, was associated with reduced risk of clear-cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. As for the 3′ untranslated region (UTR) polymorphic site rs4848300, a borderline significant association was found. Similarly, as for IL1B rs7596684 genotypes, borderline significant association was found. No association was found for IL1A rs3783516 or rs2856838 genotypes (26). In 2014, Zhang and colleagues examined a functional insertion/deletion polymorphism rs3783553 at a miR-122 binding site in the 3′UTR of IL1A in 301 Chinese women with epithelial ovarian cancer and 240 healthy controls (27). The genotypic and allelic distributions differed significantly between cases and controls, with the variant homozygote insertion/insertion associated with a reduced risk of ovarian cancer (27). Clinically, carriers of the deletion/insertion genotype tended to be diagnosed at earlier stages (I–II) and were more likely to achieve optimal cytoreductive surgery comparing with those carrying deletion/deletion genotype (OR=0.230, 95% CI=0.122-0.435, p=0.0001). In survival analyses, advanced stage and suboptimal cytoreduction were poor prognostic factors, but cytoreduction status emerged as the only independent predictor in multivariate models (27). Because rs3783553 affects miR-122 binding, the protective insertion/insertion genotype is likely to alter IL1A expression, modulating inflammatory signaling and the tumor microenvironment. In 2017, Ben Ahmed and colleagues assessed IL1 family polymorphisms in 62 Tunisian patients with ovarian cancer and 126 healthy women (28). For IL1B rs16944, the homozygous CC genotype conferred an increased risk of ovarian cancer (OR=3.08, 95% CI=1.19-7.94, p=0.0339), while the CT genotype was not associated with altered risk (OR=0.66, 95% CI=0.30-1.42, p=0.3888) (28). Given that these polymorphisms are known to influence IL1A, IL1B and IL1RA levels, the results link functionally relevant IL1 signaling variants to ovarian cancer susceptibility.

IL6 Polymorphisms in Ovarian Cancer

In 2004, using the American cohort described above, Bushley and colleagues evaluated IL6 −174 (rs1800795) (24). The variant CG or GG genotypes were not associated with altered ovarian cancer risk (24). In 2012, White et al. examined IL6 rs10242595 genotype profile in a large multi-center consortium, reporting no significant association (26). In 2016, Lu and colleagues assessed IL6 rs1800795 in a Chinese Han population comprising 687 cases and 687 controls (29). Interestingly, IL6 rs1800795 itself did not show any association in this cohort (29), consistent with the previous finding of Bushley et al. (24). In 2020, Ben Ahmed and colleagues adapted the strategy, although they collected a smaller cohort (71 patients with ovarian cancer and 74 controls). However, they assessed eight IL6 single nucleotide polymorphisms (SNPs), rs1880242, rs2069827, rs1800797, rs1800796, rs1800795, rs1474348, rs1474347 and rs2069845, systematically at the same time (39). They found that the major G allele at rs1880242 of IL6 was positively associated with ovarian cancer (OR=1.88, 95% CI=1.03-3.46, p=0.0275). Conversely, the presence of the minor T allele at this locus (GT+TT) appeared to be protective (OR=0.38, 95% CI=0.17-0.88, p=0.021). Haplotype analysis identified IL6 haplotypes GGAGGGGA and GGAGGGTA as risky haplotypes, whereas TGGGCCTA was negatively associated with ovarian cancer risk (39). In 2021, Hashemzehi and colleagues assessed IL6 rs1800795. In addition, they evaluated the association of another promoter polymorphic site, IL6 −572 (rs1800796), with susceptibility to ovarian cancer in an Iranian population consisting of 131 ovarian cancer cases and 140 non-cancer healthy controls (30). Differently from previous negative studies, they found a significant association of the IL6 rs1800795 CC genotype (OR=3.23, 95% CI=1.13-9.24, p=0.029) and C allele (OR=1.915; 95% CI=1.27-2.90, p=0.002) with an increased risk of ovarian cancer. As for the IL6 rs1800796 genotype, no association was found (30). IL6 has been reported to be multi-functional pro-inflammatory cytokine that has crucial roles in tumor progression through tumor growth promotion, anti-apoptotic activity, and modulation of immune function (40-42). These data highlight the complexity of IL6 signaling in ovarian cancer, with context-dependent pro- and antitumor effects and important roles for multi-SNP haplotypes.

IL8 Polymorphisms in Ovarian Cancer

In 2015, Koensgen and colleagues evaluated four IL8 SNPs, −251 (rs4073), +781 (rs2227306), +1633 (rs2227543), +2767 (rs1126647) in 268 patients with ovarian cancer and 426 healthy women in Germany (31). They observed the TT genotype of IL8 rs2227306 was significantly associated with an increased risk of ovarian cancer (p=0.0048), whereas the CC genotype was associated with significantly reduced risk (p=0.0003). In addition, the TT genotype of IL8 rs1126647 was also associated with elevated ovarian cancer risk (p=0.0177) (31). In 2024, Watrowski and colleagues validated Koensgen et al.’s finding focused on menopausal status and endometriosis-related subtypes of ovarian cancer in a cohort of women of Central European descent, consisting of 200 patients with ovarian cancer and 213 healthy controls (32). Overall, none of the four SNPs were associated with ovarian cancer risk in co-dominant, dominant, recessive, over-dominant, nor allelic frequency analysis models (all p>0.05). Among postmenopausal women, genotypes of three out of the four investigated SNPs, rs4073, rs2227306, and rs2227543, were associated with altered ovarian cancer risk (32). The positive results of the studies led to bioinformatical research focusing on predictive IL8 markers which affect the protein structure (43). These findings support genotypes of IL8 as having most potential, compared with other IL members, as both a biomarker and functional mediator of ovarian cancer pathogenesis. However, further investigations of their functional role and impact on susceptibility to ovarian cancer remains uncertain in different populations, for instance Asia populations, for IL8 polymorphisms to serve as potential biomarkers for ovarian cancer risk assessment.

IL10 Polymorphisms in Ovarian Cancer

In 2004, Bushley and colleagues also investigated the influence of IL10 rs1800896 and rs1800871 genotypes on ovarian cancer risk in the American cohort described above (24). Although no association with overall risk was identified, variant carriers were less likely to present with advanced-stage disease (24). Three years later, Braicu and colleagues also assessed the contribution of IL10 genotypes to ovarian cancer risk in 129 non-cancer controls and 147 ovarian cancer cases in Germany (25). The authors not only aimed at validating the contributions of IL10 rs1800896 and rs1800872 genotypes to ovarian cancer, but also at evaluating the influence of another promoter −819 (rs1800871) polymorphic site (24). To date, all the results regarding the association of IL10 genotype with ovarian cancer susceptibility have given negative findings. Although seeking IL10 genotypic markers for ovarian cancer seemed not to be the focus of epidemiological studies, scientists have maintained an interest in revealing the involvement of IL10 in ovarian carcinogenesis and prognosis. For instance, IL10 has been shown to be present at high levels in the ascites of ovarian cancer cases (44, 45), and patients with high ascites levels of IL10 have worse outcomes (46). The significant alterations at its proteomic level among patients with ovarian cancer highlights the potential role of IL10 as an immunomodulator in the tumor microenvironment, leading to immune evasion of ovarian cancer.

IL16 Polymorphisms in Ovarian Cancer

In 2024, Watrowski and colleagues investigated the contribution of IL16 rs11556218, rs4778889, rs4072111, and rs1131445 genotypes to ovarian cancer in the previously mentioned cohort (33). They found significant associations of IL16 rs11556218 with elevated ovarian cancer risk in the whole cohort (OR=2.76, 95% CI=1.84-4.14, p=0.0001) and in both premenopausal (p=0.001) and postmenopausal (p=0.001) subgroups. In the whole cohort, the CT+CC genotypes of IL16 rs4778889 were associated with ovarian cancer risk (OR=1.65, 95% CI=1.08-2.50, p=0.020), and the IL16 rs4778889 CC genotype was associated with ovarian cancer risk predominantly in premenopausal women (p<0.0001). In addition, IL16 rs4778889 CC genotype was associated with high-grade serous ovarian cancer (p=0.036) and endometriosis-related ovarian cancer subtypes (p=0.002). It is highlighted that IL16 genotypes were found to serve as predictive markers for subtypes of ovarian cancer. For IL16 rs4072111 and rs1131445, no significant associations with ovarian cancer risk were found for either genotype (33).

IL18 Polymorphisms in Ovarian Cancer

Bushley and colleagues were also the first group to investigate the contribution of IL18 genotype to ovarian cancer risk. They evaluated the influence of IL18 −137 (rs187238) in their American cohort mentioned above (24). They found that IL18 variant genotypes at rs187238 were not associated with ovarian cancer risk (p for trend=0.73). Interestingly, cases with IL18 GC or CC genotypes at rs187238 were less likely to be diagnosed with disease at regional/distant stages (OR=0.51, 95% CI=0.28-0.90, p=0.04). The results raised translational scientists’ interest in IL18 as a predictive marker for ovarian cancer. In 2008, Palmieri and colleagues conducted a multi-center case–control study within the Ovarian Cancer Association Consortium, genotyping 1,536 SNPs in inflammation and related pathways in 848 ovarian cancer cases and 798 controls from the North Carolina Ovarian Cancer Study, followed by replication in additional cohorts (34). They identified the G allele of rs1834481 of IL18 as being associated with ovarian cancer risk in non-Hispanic White women (OR=1.24, 95% CI=1.06-1.45, p=0.0007), it emerging from a broader pathway-based screen of candidate genes. However, when extended to multiple cohorts from various countries, including USA, German, Denmark, and Australia, the significant association seemed to be null (OR=1.24, 95% CI=1.06-1.45, p=0.7665). One explanation may be that the rs1834481 genotype of IL18 as an ovarian cancer marker is ethnic-specific. This work provides early evidence that variation in IL18, a key interferon-γ-inducing cytokine, may modulate ovarian cancer susceptibility. In the year after, Dehaghani and colleagues examined two promoter SNPs in IL18, −607 (rs1946518) and −137 (rs187238), in 85 Iranian women with ovarian cancer and 158 healthy controls. They found no significant association between these promoter variants and ovarian cancer risk, from the aspects of allelic frequency, genotypic, and haplotypic analysis (35). However, serum IL18 levels measured by enzyme-linked immunosorbent assay were significantly higher in patients than in controls (p=0.008), independent of genotype or stage. Taken together, these findings suggest that dysregulation of IL18 expression is a feature of ovarian cancer (elevated serum levels), but not all IL18 polymorphisms contribute equally to risk. Promoter variants rs1946518 and rs187238 may have a neutral effect in some populations. In 2012, White and colleagues conducted a genome-wide analysis study investigating the contributions of inherited inflammation-related genotypes to ovarian cancer in the international cohorts described above (26). They found that neither IL18 rs4937113 nor rs2043055 genotypes were associated with ovarian cancer risk (26). Functionally, IL18 can support anti-tumor Th1 and natural killer responses, but in certain microenvironments, it also promotes angiogenesis, immune evasion and metastasis (47, 48). The net effect of IL18 variants likely depends on their impact on expression and on the cytokine milieu.

IL23 Polymorphisms in Ovarian Cancer

In 2010, Zhang and colleagues analyzed three tag SNPs in IL23 receptor (IL23R) in 96 Han Chinese women with histologically confirmed ovarian cancer and 115 healthy controls (36). They found a significant association for rs10889677 in the 3′UTR of IL23R. The C allele was more frequent in cases (0.281) than controls (0.183; OR=1.75, 95% CI=1.11-2.77). This suggests that IL23R rs10889677 C allele carriers are at higher risk for ovarian cancer in this population. When stratified by stage, they also observed that allelic frequencies at rs11465817 differed between early (I-II) and advanced (III-IV) disease. The A allele was enriched in those with advanced-stage tumors (OR=2.09, 95% CI=1.08-4.02, p=0.027), implying a potential role in disease progression. Because IL23/IL23R signaling promotes Th17 differentiation, chronic inflammation and angiogenesis (49), these data support the concept that genetically driven variations in IL23/IL23R-related pathway influence both ovarian cancer susceptibility and its aggressiveness.

IL31 and IL32 Polymorphisms in Ovarian Cancer

In 2018, Liu and colleagues studied two IL31 SNPs, rs7977932 and rs4758680, in 412 patients with ovarian cancer and 428 controls in a Chinese population (37). For rs7977932, the CG and GG genotypes were less frequent in ovarian cancer cases than controls (9.9% vs. 16.8% and 0.7% vs. 1.2%, respectively), suggesting a protective effect (OR=0.54, 95% CI=0.36-0.82, p=0.0045; and OR=0.57, 95% CI=0.14-2.44, p=0.4972). CG and GG genotypes combined were also significantly associated with reduced ovarian cancer risk (OR=0.55, 95% CI=0.37-0.81, p=0.0035). For rs4758680, the CA and AA genotypes were more frequent in patients with ovarian cancer (34.2% vs. 26.6% and 4.6% vs. 4.0%, respectively), indicating increased susceptibility (OR=1.45, 95% CI=1.09-1.96, p=0.0162; and OR=1.32, 95% CI=0.67-2.56, p=0.5293). CA and AA genotypes combined were also significantly associated with increased ovarian cancer risk (OR=1.45, 95% CI=1.09-1.92, p=0.0150). Clinically, rs7977932 CG/GG carriers were more likely to have less advanced ovarian cancer (earlier stage), and Kaplan–Meier analysis showed that these genotypes were associated with a reduced risk of recurrence compared to CC homozygotes (37). In 2020, Luo and colleagues analyzed the IL32 rs28372698 genotypes in the Chinese Han cohort mentioned above (38). The TT homozygous genotype was significantly more frequent in cases than in controls (12.9% vs. 6.2%; OR=2.09, 95% CI=1.06-4.14, p=0.0483), indicating that TT is a risky genotype for ovarian cancer (38). Since IL31 and IL32 are both pro-inflammatory cytokines associated with multiple malignancies, these studies provide initial evidence that genetic variation of IL31 and/or IL32 may contribute to ovarian cancer susceptibility and might serve as markers of progression.

TNFA Polymorphisms in Ovarian Cancer

In 2017, Ben Ahmed and colleagues also assessed TNF genotypes in addition to IL1 genotypes among 62 Tunisian patients with ovarian cancer and 126 healthy women (28). The authors found that TNFA −308 (rs1800629) heterozygous variant G/A genotype was associated with increased ovarian cancer risk (OR=3.88, 95% CI=1.52-9.90, p=0.0052), and the TNFA rs1800629 homozygous variant AA genotype was also risky (OR=4.87, 95% CI=1.48-16.05, p=0.0156) (28).

TGFB1 Polymorphisms in Ovarian Cancer

In the same Tunisian cohort mentioned above, Ben Ahmed and colleagues also assessed three SNPs of TGFB1 (rs1800470, rs1800472, rs1800469) (39). They found no difference in minor allelic frequencies for the three TGFB1 SNPs overall, but a significant negative association between the rs1800469 CT genotype and ovarian cancer (OR=0.24, 95% CI=0.15-0.58, p=0.0035), suggesting a protective effect. Furthermore, patients carrying TGFB1 CT or TT genotype had a substantially reduced risk for ovarian cancer (OR=0.33, 95% CI=0.15-0.74, p=0.0166) (39).

NFKB and Polymorphisms of Genes for Adhesion Molecules in Ovarian Cancer

In 2016, Lu and colleagues investigated six polymorphisms in inflammatory response genes, peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala (rs1801282), selectin E (SELE) S128R (rs5361), transforming growth factor beta 1 (NFKB1) −94 ATTG insertion/deletion (rs28362491), nuclear factor kappa B inhibitor alpha (NFKBIA) −826C/T (rs2233406), and intercellular adhesion molecule 1 (ICAM1) K469E (rs5498), in 687 Chinese ovarian cancer cases and 687 controls (29). They have several key findings. Regarding PPARG rs1801282, the CG genotype was associated with increased risk (OR=1.52, 95% CI=1.01-2.29, p=0.040). For SELE rs5361, the AC genotype conferred reduced risk (OR=0.57, 95% CI=0.34-0.94, p=0.0345). For NFκB1 rs28362491, the insertion/insertion homozygote was associated with increased risk (OR=1.39, 95% CI=1.00-1.92, p=0.050). Regarding ICAM1 rs5498, the AG genotype was associated with reduced risk (OR=0.77, 95% CI=0.60-0.98, p=0.0422) (29). Lastly, a combined genotype of NFKB1 deletion/deletion plus NFKBIA TT was associated with a substantially reduced risk (OR=0.12, 95% CI=0.01-0.95, p=0.040) (29). All the above results implicate NFκB transcriptional activity in modulation of ovarian cancer susceptibility via ICAM1 and SELE.

Limitations

There are several methodological constraints should be kept in mind. The first concerns the candidate-gene design. Most studies tested a limited number of genotypic variants selected a priori, which risks missing causal ovarian cancer and is vulnerable to publication bias. Secondly, the sample size and analytical power were limited. While some cohorts were moderately sized (usually with a total of 500 to 700 cases and controls), several studies recruited fewer than even 100 ovarian cancer cases, limiting their power to detect modest effects and increasing false-positive risk. Thirdly, there is the heterogeneity of inclusion/exclusion criteria. Differences in inclusion criteria, such as “all ovarian cancer” versus “epithelial high-grade”, or “ovarian cancer” broadly defined, inclusion/exclusion of borderline tumors, and in treatment eras introduce heterogeneity. Other common limitations for epidemiological studies also suggest the need for improvement. For instance, not all studies adjusted thoroughly for multiple comparisons, and independent replication across populations was often lacking. In addition, for many SNPs examined, functional consequences were inferred but not directly demonstrated in ovarian tissue or relevant immune cells.

Summary and Discussion

Across the studies mentioned above, we found consistent patterns for risky and protective variant genotypes. Risky variant genotypes often map to that are known or predicted to enhance pro-inflammatory or pro-angiogenic signaling in ovarian cancer, such as IL1B rs16944 CC, IL6 rs1800795, IL8 rs2227306 TT, IL8 rs1126647 TT, IL16 rs11556218 GT/GG, IL16 rs4778889 CT/CC, IL23R rs10889677 AC/CC, IL31 rs4758680 CA/AA, IL32 rs28372698 TT, TNFA rs1800629 GA/AA, and PPARG rs1801282 CG genotypes (Table I). Regarding protective variant genotypes, they frequently correspond to those alleles that reduce inflammatory tone or rebalance cytokine networks, such as IL1A rs17561 GT/TT, IL1A rs4848300 CT/CC, IL1A rs3783553 insertion/insertion, IL1B rs7596684 CT/CC, IL6 rs1880242 GT/TT, IL31 rs7977932 CG/GG, TGFβ1 rs1800469 CT/TT, SELE rs5361 AC, ICAM1 rs5498 AG genotypes and specific IL6 haplotypes (Table I).

View this table:
Table I.

Overview of potential inflammatory cytokine genotypic markers for ovarian cancer.

Beyond risk per se, several polymorphisms are predictive markers for ovarian cancer features. They may include IL23R rs11465817 A allele for advanced stage disease (36). IL1A rs3783553 deletion/insertion for earlier stage and more frequent optimal cytoreduction (27). IL31 rs7977932 CG/GG for earlier stage and reduced recurrence (37). These point toward potential roles of these specific genotypes in influencing tumor biology, surgical resectability and long-term outcomes.

As shown in Table I, these studies focused on investigating the inflammatory-related genotypes in mixed non-Hispanic White (34), Iranian (IL18 promoters, serum IL18) (35), Chinese Han (IL1F, IL23R, IL31, IL32, and NFKB genes for adhesion molecules) (27, 29, 36-38), German (IL8) (31), and Tunisian (IL1B, IL6, TNFA and TGFB1) (28, 39) women. Both sample sizes and representation for various populations in the previous literature are far from satisfying. Allelic frequencies and linkage disequilibrium patterns differ substantially across these populations, which can influence both statistical power and the observed magnitude/direction of associations. As such, replication across ethnicities is crucial before incorporating any given cytokine SNP into universal risk models.

Conclusion and Future Directions

The collective evidence from these 10 studies supports the concept that inherited variation in inflammatory cytokine networks, spanning the IL1 family, IL6, IL8, IL16, IL18, IL23R, IL31, IL32, TNFA, TGFB1 and NFKB/genes for adhesion molecules, contributes to ovarian cancer susceptibility and, in some cases, to disease progression and recurrence. Most risk-increasing alleles are consistent with a pro-inflammatory, pro-angiogenic, or immunosuppressive microenvironment, while protective variants tend to dampen or rebalance these signals.

For future work, several directions appear particularly promising. Firstly, epidemiological scientists are encouraged to establish pathway-level and polygenic modeling. Rather than focusing on single SNPs, constructing polygenic risk scores specific to inflammatory pathways, combined with reproductive and environmental risk factors, may improve risk stratification. Secondly, more functional studies are needed. Functional assays on ovarian surface epithelium, fallopian tube epithelium, tumor cells and immune/stromal cells are needed to clarify how specific variants alter cytokine expression, downstream signaling and cellular behavior. Thirdly, genome-wide approaches with dense coverage of cytokine ovarian cancer across diverse populations can refine causal variants and distinguish true signals from linkage disequilibrium proxies. Fourthly, clinical translation from studies of inflammatory cytokine genotypic markers for ovarian cancer should catch up with other types of cancer, such as lung, breast and colorectal cancer. That is to say, polymorphisms that influence not only risk but also tumor stage, surgical resectability or recurrence (for instance, IL1A rs3783553 and IL31 rs7977932) merit evaluation as components of prognostic models or as biomarkers for selecting patients for cytokine-targeted or immunomodulatory therapies.

Overall, the current body of work provides a biologically coherent, although still incomplete, picture. Chronic, genetically modulated inflammation is not merely a bystander but an integral driver of epithelial ovarian carcinogenesis. Further rigorous, multi-disciplinary research will be needed to translate these insights into tangible tools for prevention, early detection and personalized management. Moreover, further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management.

Footnotes

  • Authors’ Contributions

    WSC, CWT, JCC, YCW and DTB contributed to the conceptualization, drafting and revision of the manuscript. WSC, YCW and CWT contributed to reviewing and editing. JCC and DTB contributed to the supervision. All Authors contributed to the article and approved the submitted version.

  • Conflicts of Interest

    All the Authors declare no conflicts of interest regarding this study.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received January 27, 2026.
  • Revision received February 24, 2026.
  • Accepted February 26, 2026.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

References

  1. ↵
    1. Siegel RL,
    2. Kratzer TB,
    3. Giaquinto AN,
    4. Sung H,
    5. Jemal A
    : Cancer statistics, 2025. CA Cancer J Clin 75(1): 10-45, 2025. DOI: 10.3322/caac.21871
    OpenUrlCrossRefPubMed
  2. ↵
    1. Bray F,
    2. Laversanne M,
    3. Sung H,
    4. Ferlay J,
    5. Siegel RL,
    6. Soerjomataram I,
    7. Jemal A
    : Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3): 229-263, 2024. DOI: 10.3322/caac.21834
    OpenUrlCrossRefPubMed
  3. ↵
    1. Zhou Z,
    2. Wang X,
    3. Ren X,
    4. Zhou L,
    5. Wang N,
    6. Kang H
    : Disease burden and attributable risk factors of ovarian cancer from 1990 to 2017: findings from the Global Burden of Disease Study 2017. Front Public Health 9: 619581, 2021. DOI: 10.3389/fpubh.2021.619581
    OpenUrlCrossRefPubMed
  4. ↵
    1. Marth C,
    2. Abreu MH,
    3. Andersen KK,
    4. Aro KM,
    5. de Lurdes Batarda M,
    6. Boll D,
    7. Ekmann-Gade AW,
    8. Haltia UM,
    9. Hansen J,
    10. Haug AJ,
    11. Høgdall C,
    12. Korach J,
    13. Lassus H,
    14. Lindemann K,
    15. Van Nieuwenhuysen E,
    16. Ottevanger PB,
    17. Polterauer S,
    18. Schnack TH
    : Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial). Cancer 128(16): 3080-3089, 2022. DOI: 10.1002/cncr.34350
    OpenUrlCrossRefPubMed
  5. ↵
    1. Matsas A,
    2. Stefanoudakis D,
    3. Troupis T,
    4. Kontzoglou K,
    5. Eleftheriades M,
    6. Christopoulos P,
    7. Panoskaltsis T,
    8. Stamoula E,
    9. Iliopoulos DC
    : Tumor markers and their diagnostic significance in ovarian cancer. Life (Basel) 13(8): 1689, 2023. DOI: 10.3390/life13081689
    OpenUrlCrossRefPubMed
    1. Philpott S,
    2. Raikou M,
    3. Manchanda R,
    4. Lockley M,
    5. Singh N,
    6. Scott M,
    7. Evans DG,
    8. Adlard J,
    9. Ahmed M,
    10. Edmondson R,
    11. Woodward ER,
    12. Lamnisos A,
    13. Balega J,
    14. Brady AF,
    15. Sharma A,
    16. Izatt L,
    17. Kulkarni A,
    18. Tripathi V,
    19. Solomons JS,
    20. Hayes K,
    21. Hanson H,
    22. Snape K,
    23. Side L,
    24. Skates S,
    25. McGuire A,
    26. Rosenthal AN
    : The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2. J Med Genet 60(5): 440-449, 2023. DOI: 10.1136/jmg-2022-108741
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Erol A,
    2. Niemira M,
    3. Krętowski AJ
    : Novel approaches in ovarian cancer research against heterogeneity, late diagnosis, drug resistance, and transcoelomic metastases. Int J Mol Sci 20(11): 2649, 2019. DOI: 10.3390/ijms20112649
    OpenUrlCrossRefPubMed
  8. ↵
    1. Chen H,
    2. Zhai Z,
    3. Xie Q,
    4. Lai Y,
    5. Chen G
    : Correlation between SNPs of PIK3CA, ERBB2 3′UTR, and their interactions with environmental factors and the risk of epithelial ovarian cancer. J Assist Reprod Genet 38(10): 2631-2639, 2021. DOI: 10.1007/s10815-021-02177-2
    OpenUrlCrossRefPubMed
  9. ↵
    1. Pearce CL,
    2. Rossing MA,
    3. Lee AW,
    4. Ness RB,
    5. Webb PM, for Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group,
    6. Chenevix-Trench G,
    7. Jordan SM,
    8. Stram DA,
    9. Chang-Claude J,
    10. Hein R,
    11. Nickels S,
    12. Lurie G,
    13. Thompson PJ,
    14. Carney ME,
    15. Goodman MT,
    16. Moysich K,
    17. Hogdall E,
    18. Jensen A,
    19. Goode EL,
    20. Fridley BL,
    21. Cunningham JM,
    22. Vierkant RA,
    23. Weber RP,
    24. Ziogas A,
    25. Anton-Culver H,
    26. Gayther SA,
    27. Gentry-Maharaj A,
    28. Menon U,
    29. Ramus SJ,
    30. Brinton L,
    31. Wentzensen N,
    32. Lissowska J,
    33. Garcia-Closas M,
    34. Massuger LF,
    35. Kiemeney LA,
    36. Van Altena AM,
    37. Aben KK,
    38. Berchuck A,
    39. Doherty JA,
    40. Iversen E,
    41. McGuire V,
    42. Moorman PG,
    43. Pharoah P,
    44. Pike MC,
    45. Risch H,
    46. Sieh W,
    47. Stram DO,
    48. Terry KL,
    49. Whittemore A,
    50. Wu AH,
    51. Schildkraut JM,
    52. Kjaer SK, Ovarian Cancer Association Consortium
    : Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer Epidemiol Biomarkers Prev 22(5): 880-890, 2013. DOI: 10.1158/1055-9965.EPI-12-1030-T
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Edwards RP,
    2. Huang X,
    3. Vlad AM
    : Chronic inflammation in endometriosis and endometriosis-associated ovarian cancer: New roles for the “old” complement pathway. Oncoimmunology 4(5): e1002732, 2015. DOI: 10.1080/2162402X.2014.1002732
    OpenUrlCrossRefPubMed
    1. Zeng Y,
    2. Wang C,
    3. Yang C,
    4. Shan X,
    5. Meng XQ,
    6. Zhang M
    : Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications. Hum Reprod 39(8): 1599-1607, 2024. DOI: 10.1093/humrep/deae132
    OpenUrlCrossRefPubMed
  12. ↵
    1. Kisielewski R,
    2. Mazurek A,
    3. Laudański P,
    4. Tołwińska A
    : Inflammation and ovarian cancer – current views. Ginekol Pol 84(4): 293-297, 2013. DOI: 10.17772/gp/1579
    OpenUrlCrossRefPubMed
  13. ↵
    1. Trabert B,
    2. Tworoger SS,
    3. O’Brien KM,
    4. Townsend MK,
    5. Fortner RT,
    6. Iversen ES,
    7. Hartge P,
    8. White E,
    9. Amiano P,
    10. Arslan AA,
    11. Bernstein L,
    12. Brinton LA,
    13. Buring JE,
    14. Dossus L,
    15. Fraser GE,
    16. Gaudet MM,
    17. Giles GG,
    18. Gram IT,
    19. Harris HR,
    20. Bolton JH,
    21. Idahl A,
    22. Jones ME,
    23. Kaaks R,
    24. Kirsh VA,
    25. Knutsen SF,
    26. Kvaskoff M,
    27. Lacey JV,
    28. Lee IM,
    29. Milne RL,
    30. Onland-Moret NC,
    31. Overvad K,
    32. Patel AV,
    33. Peters U,
    34. Poynter JN,
    35. Riboli E,
    36. Robien K,
    37. Rohan TE,
    38. Sandler DP,
    39. Schairer C,
    40. Schouten LJ,
    41. Setiawan VW,
    42. Swerdlow AJ,
    43. Travis RC,
    44. Trichopoulou A,
    45. van den Brandt PA,
    46. Visvanathan K,
    47. Wilkens LR,
    48. Wolk A,
    49. Zeleniuch-Jacquotte A,
    50. Wentzensen N, Ovarian Cancer Cohort Consortium (OC3)
    : The risk of ovarian cancer increases with an increase in the lifetime number of ovulatory cycles: an analysis from the Ovarian Cancer Cohort Consortium (OC3). Cancer Res 80(5): 1210-1218, 2020. DOI: 10.1158/0008-5472.CAN-19-2850
    OpenUrlAbstract/FREE Full Text
    1. Phung MT,
    2. Muthukumar A,
    3. Trabert B,
    4. Webb PM,
    5. Jordan SJ,
    6. Terry KL,
    7. Cramer DW,
    8. Titus LJ,
    9. Risch HA,
    10. Doherty JA,
    11. Harris HR,
    12. Goodman MT,
    13. Modugno F,
    14. Moysich KB,
    15. Jensen A,
    16. Kjaer SK,
    17. Anton-Culver H,
    18. Ziogas A,
    19. Berchuck A,
    20. Khoja L,
    21. Wu AH,
    22. Pike MC,
    23. Pearce CL,
    24. Lee AW
    : Effects of risk factors for ovarian cancer in women with and without endometriosis. Fertil Steril 118(5): 960-969, 2022. DOI: 10.1016/j.fertnstert.2022.07.019
    OpenUrlCrossRefPubMed
    1. Gunderson CC,
    2. Ding K,
    3. Dvorak J,
    4. Moore KN,
    5. McMeekin DS,
    6. Benbrook DM
    : The pro-inflammatory effect of obesity on high grade serous ovarian cancer. Gynecol Oncol 143(1): 40-45, 2016. DOI: 10.1016/j.ygyno.2016.07.103
    OpenUrlCrossRefPubMed
  16. ↵
    1. Piao J,
    2. Lee EJ,
    3. Lee M
    : Association between pelvic inflammatory disease and risk of ovarian cancer: An updated meta-analysis. Gynecol Oncol 157(2): 542-548, 2020. DOI: 10.1016/j.ygyno.2020.02.002
    OpenUrlCrossRefPubMed
  17. ↵
    1. Sköld C,
    2. Corvigno S,
    3. Dahlstrand H,
    4. Enblad G,
    5. Mezheyeuski A,
    6. Sundström-Poromaa I,
    7. Stålberg K,
    8. Tolf A,
    9. Glimelius I,
    10. Koliadi A
    : Association between parity and pregnancy-associated tumor features in high-grade serous ovarian cancer. Cancer Causes Control 35(8): 1101-1109, 2024. DOI: 10.1007/s10552-024-01876-2
    OpenUrlCrossRefPubMed
    1. Schock H,
    2. Fortner RT,
    3. Surcel HM,
    4. Grankvist K,
    5. Pukkala E,
    6. Lehtinen M,
    7. Lundin E
    : Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study. Int J Cancer 137(2): 439-447, 2015. DOI: 10.1002/ijc.29387
    OpenUrlCrossRefPubMed
    1. Avramenko AS,
    2. Flanagan JM
    : An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use. Clin Epigenetics 15(1): 165, 2023. DOI: 10.1186/s13148-023-01584-9
    OpenUrlCrossRefPubMed
  20. ↵
    1. Wu AH,
    2. Pearce CL,
    3. Lee AW,
    4. Tseng C,
    5. Jotwani A,
    6. Patel P,
    7. Pike MC
    : Timing of births and oral contraceptive use influences ovarian cancer risk. Int J Cancer 141(12): 2392-2399, 2017. DOI: 10.1002/ijc.30910
    OpenUrlCrossRefPubMed
  21. ↵
    1. Ullah A,
    2. Chen Y,
    3. Singla RK,
    4. Cao D,
    5. Shen B
    : Pro-inflammatory cytokines and CXC chemokines as game-changer in age-associated prostate cancer and ovarian cancer: Insights from preclinical and clinical studies’ outcomes. Pharmacol Res 204: 107213, 2024. DOI: 10.1016/j.phrs.2024.107213
    OpenUrlCrossRefPubMed
  22. ↵
    1. Wang W,
    2. Wu J,
    3. Mukherjee A,
    4. He T,
    5. Wang XY,
    6. Ma Y,
    7. Fang X
    : Lysophosphatidic acid induces tumor necrosis factor-alpha to regulate a pro-inflammatory cytokine network in ovarian cancer. FASEB J 34(10): 13935-13948, 2020. DOI: 10.1096/fj.202001136R
    OpenUrlCrossRefPubMed
  23. ↵
    1. Hefler LA,
    2. Ludwig E,
    3. Lebrecht A,
    4. Zeillinger R,
    5. Tong-Cacsire D,
    6. Koelbl H,
    7. Leodolter S,
    8. Tempfer CB
    : Polymorphisms of the interleukin-1 gene cluster and ovarian cancer. J Soc Gynecol Investig 9(6): 386-390, 2002.
    OpenUrlCrossRefPubMed
  24. ↵
    1. Bushley AW,
    2. Ferrell R,
    3. McDuffie K,
    4. Terada KY,
    5. Carney ME,
    6. Thompson PJ,
    7. Wilkens LR,
    8. Tung KH,
    9. Ness RB,
    10. Goodman MT
    : Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer. Gynecol Oncol 95(3): 672-679, 2004. DOI: 10.1016/j.ygyno.2004.08.024
    OpenUrlCrossRefPubMed
  25. ↵
    1. Ioana Braicu E,
    2. Mustea A,
    3. Toliat MR,
    4. Pirvulescu C,
    5. Könsgen D,
    6. Sun P,
    7. Nürnberg P,
    8. Lichtenegger W,
    9. Sehouli J
    : Polymorphism of IL-1α, IL-1β and IL-10 in patients with advanced ovarian cancer: Results of a prospective study with 147 patients. Gynecol Oncol 104(3): 680-685, 2007. DOI: 10.1016/j.ygyno.2006.10.014
    OpenUrlCrossRefPubMed
  26. ↵
    1. White KL,
    2. Schildkraut JM,
    3. Palmieri RT,
    4. Iversen ES Jr.,
    5. Berchuck A,
    6. Vierkant RA,
    7. Rider DN,
    8. Charbonneau B,
    9. Cicek MS,
    10. Sutphen R,
    11. Birrer MJ,
    12. Pharoah PP,
    13. Song H,
    14. Tyrer J,
    15. Gayther SA,
    16. Ramus SJ,
    17. Wentzensen N,
    18. Yang HP,
    19. Garcia-Closas M,
    20. Phelan CM,
    21. Cunningham JM,
    22. Fridley BL,
    23. Sellers TA,
    24. Goode EL, Ovarian Cancer Association Consortium
    : Ovarian cancer risk associated with inherited inflammation-related variants. Cancer Res 72(5): 1064-1069, 2012. DOI: 10.1158/0008-5472.CAN-11-3512
    OpenUrlAbstract/FREE Full Text
  27. ↵
    1. Zhang Z,
    2. Zhou B,
    3. Gao Q,
    4. Wu Y,
    5. Zhang K,
    6. Pu Y,
    7. Song Y,
    8. Zhang L,
    9. Xi M
    : A polymorphism at miRNA-122-binding site in the IL-1α 3′UTR is associated with risk of epithelial ovarian cancer. Fam Cancer 13(4): 595-601, 2014. DOI: 10.1007/s10689-014-9739-y
    OpenUrlCrossRefPubMed
  28. ↵
    1. Ahmed AB,
    2. Zidi S,
    3. Sghaier I,
    4. Ghazouani E,
    5. Mezlini A,
    6. Almawi W,
    7. Loueslati BY
    : Common variants in IL-1RN, IL-1β and TNF-α and the risk of ovarian cancer: a case control study. Cent Eur J Immunol 42(2): 150-155, 2017. DOI: 10.5114/ceji.2017.69356
    OpenUrlCrossRefPubMed
  29. ↵
    1. Lu ZH,
    2. Gu XJ,
    3. Shi KZ,
    4. Li X,
    5. Chen DD,
    6. Chen L
    : Association between genetic polymorphisms of inflammatory response genes and the risk of ovarian cancer. J Formos Med Assoc 115(1): 31-37, 2016. DOI: 10.1016/j.jfma.2015.01.002
    OpenUrlCrossRefPubMed
  30. ↵
    1. Hashemzehi A,
    2. Karimi-Zarchi M,
    3. Parsaeian SF,
    4. Asadian F,
    5. Golestanpour H,
    6. Setayesh S,
    7. Shaker SA,
    8. Zare-Shehneh M,
    9. Neamatzadeh H
    : Association of IL-6 −174G>C and −572G>C polymorphisms with susceptibility to cervical cancer and ovarian cancer. Asian Pac J Cancer Prev 22(9): 2867-2871, 2021. DOI: 10.31557/APJCP.2021.22.9.2867
    OpenUrlCrossRefPubMed
  31. ↵
    1. Koensgen D,
    2. Bruennert D,
    3. Ungureanu S,
    4. Sofroni D,
    5. Braicu EI,
    6. Sehouli J,
    7. Sümnig A,
    8. Delogu S,
    9. Zygmunt M,
    10. Goyal P,
    11. Evert M,
    12. Olek S,
    13. Biebler KE,
    14. Mustea A
    : Polymorphism of the IL-8 gene and the risk of ovarian cancer. Cytokine 71(2): 334-338, 2015. DOI: 10.1016/j.cyto.2014.07.254
    OpenUrlCrossRefPubMed
  32. ↵
    1. Watrowski R,
    2. Schuster E,
    3. Hofstetter G,
    4. Fischer MB,
    5. Mahner S,
    6. Van Gorp T,
    7. Polterauer S,
    8. Zeillinger R,
    9. Obermayr E
    : Association of four Interleukin-8 polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with ovarian cancer risk: focus on menopausal status and endometriosis-related subtypes. Biomedicines 12(2): 321, 2024. DOI: 10.3390/biomedicines12020321
    OpenUrlCrossRefPubMed
  33. ↵
    1. Watrowski R,
    2. Schuster E,
    3. Van Gorp T,
    4. Hofstetter G,
    5. Fischer MB,
    6. Mahner S,
    7. Polterauer S,
    8. Zeillinger R,
    9. Obermayr E
    : Association of the single nucleotide polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 gene with ovarian cancer. Int J Mol Sci 25(19): 10272, 2024. DOI: 10.3390/ijms251910272
    OpenUrlCrossRefPubMed
  34. ↵
    1. Palmieri RT,
    2. Wilson MA,
    3. Iversen ES,
    4. Clyde MA,
    5. Calingaert B,
    6. Moorman PG,
    7. Poole C,
    8. Anderson AR,
    9. Anderson S,
    10. Anton-Culver H,
    11. Beesley J,
    12. Hogdall E,
    13. Brewster W,
    14. Carney ME,
    15. Chen X,
    16. Chenevix-Trench G,
    17. Chang-Claude J,
    18. Cunningham JM,
    19. Dicioccio RA,
    20. Doherty JA,
    21. Easton DF,
    22. Edlund CK,
    23. Gayther SA,
    24. Gentry-Maharaj A,
    25. Goode EL,
    26. Goodman MT,
    27. Kjaer SK,
    28. Hogdall CK,
    29. Hopkins MP,
    30. Jenison EL,
    31. Blaakaer J,
    32. Lurie G,
    33. McGuire V,
    34. Menon U,
    35. Moysich KB,
    36. Ness RB,
    37. Pearce CL,
    38. Pharoah PD,
    39. Pike MC,
    40. Ramus SJ,
    41. Rossing MA,
    42. Song H,
    43. Terada KY,
    44. Vandenberg D,
    45. Vierkant RA,
    46. Wang-Gohrke S,
    47. Webb PM,
    48. Whittemore AS,
    49. Wu AH,
    50. Ziogas A,
    51. Berchuck A,
    52. Schildkraut JM, Ovarian Cancer Association Consortium, Australian Cancer Study (Ovarian Cancer Group), Australian Ovarian Cancer Study Group
    : Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women. Cancer Epidemiol Biomarkers Prev 17(12): 3567-3572, 2008. DOI: 10.1158/1055-9965.EPI-08-0548
    OpenUrlAbstract/FREE Full Text
  35. ↵
    1. Samsami Dehaghani A,
    2. Shahriary K,
    3. Kashef MA,
    4. Naeimi S,
    5. Fattahi MJ,
    6. Mojtahedi Z,
    7. Ghaderi A
    : Interleukin-18 gene promoter and serum level in women with ovarian cancer. Mol Biol Rep 36(8): 2393-2397, 2009. DOI: 10.1007/s11033-009-9469-7
    OpenUrlCrossRefPubMed
  36. ↵
    1. Zhang Z,
    2. Zhou B,
    3. Zhang J,
    4. Chen Y,
    5. Lai T,
    6. Yan L,
    7. Liang A,
    8. Li Y,
    9. Wang Y,
    10. Chen Y,
    11. Zhang L,
    12. Xi MR
    : Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer. Cancer Genet Cytogenet 196(2): 146-152, 2010. DOI: 10.1016/j.cancergencyto.2009.09.006
    OpenUrlCrossRefPubMed
  37. ↵
    1. Liu C,
    2. Wang Y,
    3. Song H,
    4. Li Q,
    5. Zhang Y,
    6. Chen P,
    7. Song Y,
    8. Su M,
    9. Huang Q,
    10. Wang M,
    11. Zhou B,
    12. Zhang L
    : Genetic association of Interleukin-31 gene polymorphisms with epithelial ovarian cancer in Chinese population. Dis Markers 2018: 3503858, 2018. DOI: 10.1155/2018/3503858
    OpenUrlCrossRefPubMed
  38. ↵
    1. Luo X,
    2. Bai P,
    3. Li Q,
    4. Zhang Y,
    5. Song Y,
    6. Su M,
    7. Huang X,
    8. Zhou B,
    9. Zhang L,
    10. Gong Y
    : Association between interleukin-32 polymorphisms and ovarian cancer in the Chinese Han population. Int J Clin Exp Pathol 13(7): 1733-1738, 2020.
    OpenUrlPubMed
  39. ↵
    1. Ahmed AB,
    2. Zidi S,
    3. Almawi W,
    4. Ghazouani E,
    5. Mezlini A,
    6. Loueslati BY,
    7. Stayoussef M
    : Single nucleotide polymorphism of transforming growth factor-β1 and interleukin-6 as risk factors for ovarian cancer. Cent Eur J Immunol 45(3): 267-275, 2020. DOI: 10.5114/ceji.2020.101242
    OpenUrlCrossRefPubMed
  40. ↵
    1. Li ZW,
    2. Wu Y,
    3. Sun Y,
    4. Liu LY,
    5. Tian MM,
    6. Feng GS,
    7. You WC,
    8. Li JY
    : Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia. World J Gastroenterol 16(14): 1788-1794, 2010. DOI: 10.3748/wjg.v16.i14.1788
    OpenUrlCrossRefPubMed
    1. Favalli EG
    : Understanding the role of Interleukin-6 (IL-6) in the joint and beyond: a comprehensive review of IL-6 inhibition for the management of rheumatoid arthritis. Rheumatol Ther 7(3): 473-516, 2020. DOI: 10.1007/s40744-020-00219-2
    OpenUrlCrossRef
  42. ↵
    1. Chonov DC,
    2. Ignatova MMK,
    3. Ananiev JR,
    4. Gulubova MV
    : IL-6 activities in the tumour microenvironment. Part 1. Open Access Maced J Med Sci 7(14): 2391-2398, 2019. DOI: 10.3889/oamjms.2019.589
    OpenUrlCrossRef
  43. ↵
    1. Haque A,
    2. Baig GA,
    3. Alshawli AS,
    4. Wali Sait KH,
    5. Mohammed Ali HSH,
    6. Hussain Sait HK,
    7. Bibi F,
    8. Pushparaj PN,
    9. Rasool M,
    10. Naseer MI
    : Effect of novel IL-8 gene mutation on its protein structure and stability among ovarian cancer patients in Saudi Arabia. Bioinformation 20(11): 1671-1677, 2024. DOI: 10.6026/9732063002001671
    OpenUrlCrossRefPubMed
  44. ↵
    1. Liu CZ,
    2. Zhang L,
    3. Chang XH,
    4. Cheng YX,
    5. Cheng HY,
    6. Ye X,
    7. Fu TY,
    8. Chen J,
    9. Cui H
    : Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer. Chin J Cancer Res 24(2): 130-137, 2012. DOI: 10.1007/s11670-012-0130-y
    OpenUrlCrossRefPubMed
  45. ↵
    1. Santin AD,
    2. Bellone S,
    3. Ravaggi A,
    4. Roman J,
    5. Smith CV,
    6. Pecorelli S,
    7. Cannon MJ,
    8. Parham GP
    : Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG 108(8): 804-808, 2001. DOI: 10.1111/j.1471-0528.2001.00206.x
    OpenUrlCrossRefPubMed
  46. ↵
    1. Guigue PA,
    2. Brezinov Y,
    3. Yasmeen A,
    4. Mbarik M,
    5. Salvador S,
    6. Lau S,
    7. Gotlieb WH,
    8. Brodeur MN
    : Ascites and serum Interleukin-10 levels as a prognostic tool for ovarian cancer outcomes. Cancers (Basel) 16(16): 2840, 2024. DOI: 10.3390/cancers16162840
    OpenUrlCrossRefPubMed
  47. ↵
    1. Dreaden KH,
    2. Pearson SP,
    3. Gurel PS,
    4. Newman RG,
    5. Zhao Y,
    6. Wang C,
    7. Heiber JF,
    8. Donatelli SS,
    9. Chamoun J,
    10. Whitmore MM
    : Interleukin-18 (IL-18) engineered for half-life extension and resistance to IL-18 binding protein (IL-18BP) to enhance anti-cancer therapeutic potential. Cytokine 193: 156979, 2025. DOI: 10.1016/j.cyto.2025.156979
    OpenUrlCrossRefPubMed
  48. ↵
    1. Liu X,
    2. Hu J,
    3. Li Y,
    4. Cao W,
    5. Wang Y,
    6. Ma Z,
    7. Li F
    : Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model. Oncol Lett 15(5): 6265-6274, 2018. DOI: 10.3892/ol.2018.8166
    OpenUrlCrossRefPubMed
  49. ↵
    1. Guo JW,
    2. Cheng YP,
    3. Liu CY,
    4. Thong HY,
    5. Lo Y,
    6. Wu CY,
    7. Jee SH
    : Magnolol may contribute to barrier function improvement on imiquimod-induced psoriasis-like dermatitis animal model via the downregulation of interleukin-23. Exp Ther Med 21(5): 448, 2021. DOI: 10.3892/etm.2021.9876
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Inflammatory Cytokine Genotypic Markers and Ovarian Cancer Risk
WEN-SHIN CHANG, CHIA-WEN TSAI, JAW-CHYUN CHEN, YUN-CHI WANG, DA-TIAN BAU
Anticancer Research May 2026, 46 (5) 2863-2876; DOI: 10.21873/anticanres.18165
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords