A two-sample Mendelian randomization analysis: causal association between chemokines and pan-carcinoma

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Cancer is a leading cause of mortality worldwide, necessitating the identification of novel risk and protective factors.
• The precise causal relationship between chemokines and cancer remains unclear due to complex biological mechanisms.

Purpose of the Study:

• To investigate the potential causal associations between serum chemokine levels and the risk of developing various cancers.
• To identify specific chemokines that may serve as biomarkers or therapeutic targets for cancer.

Main Methods:

• A bidirectional Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) data from public databases.
• The inverse-variance weighted (IVW) method was the primary analytical approach, with Bonferroni correction applied for multiple hypothesis testing.
• Sensitivity analyses, including leave-one-out methods, were performed to ensure the robustness of the findings, assessing for heterogeneity and pleiotropy.

Main Results:

• Several chemokines, including CCL1, CCL2, CCL8, CCL14, CCL22, CCL23, CCL27, and CXCL9, were identified as potential risk factors for pan-carcinoma.
• Specific associations were noted for certain chemokines with particular cancer types (e.g., CCL20 with lung and thyroid cancer, CXCL14 with colon cancer).
• A reverse causal association was observed between CCL1 and CCL18 with breast cancer, indicating a protective effect.

Conclusions:

• Chemokines are implicated as potential upstream factors in cancer pathogenesis.
• These findings suggest that chemokines could be valuable targets for future cancer prevention and treatment strategies.
• Changes in serum chemokine concentrations may serve as indicators of precancerous lesions.