Causal effects of genetically predicted CCL25 signaling on ovarian cancer risk : A 2-sample Mendelian randomization study
- 1Bao’an Clinical Institute of Shantou University Medical College, Guangdong, Shenzhen, China
- 2Shenzhen Bao’an Shiyan People’s Hospital, Guangdong, Shenzhen, China.
Abstract
Ovarian cancer (OC) is a common and highly malignant neoplasm in women, characterized by a poor prognosis and posing a significant threat to both health and quality of life. Despite the unclear pathogenesis of OC, there is growing evidence suggesting an association between OC and inflammatory cytokines. Nevertheless, this potential causal relationship remains insufficiently explored. To enhance early clinical diagnosis and inform therapeutic strategies, we conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the causal relationship between inflammatory cytokines and OC. We identified genetic instrumental variables for inflammatory cytokines and OC utilizing publicly accessible genome-wide association study data. Causal relationships between inflammatory cytokines and OC were assessed using inverse variance weighting as the primary analytical approach. The robustness and validity of the observed causal relationships were further substantiated through multiple sensitivity analyses, including Cochran Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis. Additionally, a random-effects meta-analysis was conducted to enhance statistical power and further identify causal proteins. Finally, colocalization analysis was employed to reinforce the evidence regarding the sharing of common etiological variants. MR analysis indicated that genetically predicted elevated levels of serum C-C motif chemokine 25 (CCL25) were inversely correlated with the risk of developing OC (inverse variance weighting: odds ratio = 0.95, 95% confidence interval = 0.91–0.99, P = .038). The direction of the beta coefficient was consistent across all MR methodologies. There was no evidence of horizontal pleiotropy (Egger intercept = 0.016, P = .145) or heterogeneity (Cochran Q = 8.857, P = .635). A meta-analysis confirmed that the inverse causal relationship between CCL25 and OC remained statistically significant (odds ratio = 0.94, 95% confidence interval = 0.90–0.99, P = .001). Colocalization analysis revealed no shared genetic factors between CCL25 and OC (the sum of the posterior probabilities of hypothesis 3 and hypothesis 4 is equal to 0.05.). Combined MR and meta-analyses indicate that CCL25 functions as a protective factor for OC. Future research should therefore conduct more comprehensive investigations into this relationship.
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BibTeX
@article{zhang2026causal,
title = {{Causal effects of genetically predicted CCL25 signaling on ovarian cancer risk : A 2-sample Mendelian randomization study}},
author = {Yuqiang Zhang and Li Tang and Juan Chen and Ling Yang and Zhaomei Zhong},
journal = {Medicine},
year = {2026},
month = oct,
doi = {10.1097/md.0000000000051310},
url = {https://europepmc.org/article/PMC/PMC13727187},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Causal effects of genetically predicted CCL25 signaling on ovarian cancer risk : A 2-sample Mendelian randomization study
AU - Yuqiang Zhang
AU - Li Tang
AU - Juan Chen
AU - Ling Yang
AU - Zhaomei Zhong
PY - 2026
DA - 2026/10/30
JO - Medicine
DO - 10.1097/md.0000000000051310
UR - https://europepmc.org/article/PMC/PMC13727187
AB - Ovarian cancer (OC) is a common and highly malignant neoplasm in women, characterized by a poor prognosis and posing a significant threat to both health and quality of life. Despite the unclear pathogenesis of OC, there is growing evidence suggesting an association between OC and inflammatory cytokines. Nevertheless, this potential causal relationship remains insufficiently explored. To enhance early clinical diagnosis and inform therapeutic strategies, we conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the causal relationship between inflammatory cytokines and OC. We identified genetic instrumental variables for inflammatory cytokines and OC utilizing publicly accessible genome-wide association study data. Causal relationships between inflammatory cytokines and OC were assessed using inverse variance weighting as the primary analytical approach. The robustness and validity of the observed causal relationships were further substantiated through multiple sensitivity analyses, including Cochran Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis. Additionally, a random-effects meta-analysis was conducted to enhance statistical power and further identify causal proteins. Finally, colocalization analysis was employed to reinforce the evidence regarding the sharing of common etiological variants. MR analysis indicated that genetically predicted elevated levels of serum C-C motif chemokine 25 (CCL25) were inversely correlated with the risk of developing OC (inverse variance weighting: odds ratio = 0.95, 95% confidence interval = 0.91–0.99, P = .038). The direction of the beta coefficient was consistent across all MR methodologies. There was no evidence of horizontal pleiotropy (Egger intercept = 0.016, P = .145) or heterogeneity (Cochran Q = 8.857, P = .635). A meta-analysis confirmed that the inverse causal relationship between CCL25 and OC remained statistically significant (odds ratio = 0.94, 95% confidence interval = 0.90–0.99, P = .001). Colocalization analysis revealed no shared genetic factors between CCL25 and OC (the sum of the posterior probabilities of hypothesis 3 and hypothesis 4 is equal to 0.05.). Combined MR and meta-analyses indicate that CCL25 functions as a protective factor for OC. Future research should therefore conduct more comprehensive investigations into this relationship.
SN - 0304-5412
SN - 1536-5964
SN - 0025-7974
ER -