Abstract: Objective The purpose of this study was to systematically evaluate the relationship between the ratio of ω-6/ω-3 polyunsaturated fatty acids(omega-6/omega-3 polyunsaturated fatty acids)and the risk of various types of tumors. Methods A systematic search was carried out in 9 databases(Pubmed, Embase, Web of Science, Cochrane Library, Medline, CNKI, VIP, Wanfang, CBM)up to January 31, 2024, for studies related to the association between the ratio of ω-6/ω-3PUFAs and tumor incidence risk. The quality of the finally included literature was assessed using the Newcastle-Ottawa Scale(NOS). Meta-analysis was performed using the R version 4.3.3 software. Results A total of 27 studies investigating the effect of the ratio of ω-6/ω-3PUFAs on different tumor incidence rates were included, comprising 7 cohort studies and 20 case-control studies. A total of 197,401 subjects were involved, with 81,950 cases and exposed participants and 115,451 controls and unexposed participants.Meta-analysis results showed that there was no statistically significant association between the ratio of ω-6/ω-3 PUFAs and the incidence risk of different tumors(OR=1.03, 95%CI:0.98-1.09, P=0.18). Subgroup analysis revealed that a higher ratio of ω-6/ω-3 PUFAs was associated with an increased risk of breast cancer incidence(OR=1.05, 95%CI:1.01-1.10,P=0.01), but not with prostate cancer(OR=1.26, 95%CI:0.67-2.38, P=0.47)or colorectal cancer(OR=0.99, 95%CI:0.89-1.10,P=0.85). In non-European and American regions, a higher ω-6/ω-3PUFAs ratio significantly increased the risk of various tumor incidences(OR=1.24, 95%CI:1.01-1.51, P=0.04), while in European and American regions, this association was not statistically significant(OR=1.02, 95%CI:0.97-1.07, P=0.46). When evaluating the relationship between exposure indicators and the incidence risk of various cancers, neither dietary intake(OR=1.04, 95%CI:0.98-1.09, P=0.17)nor the ratio of ω-6/ω-3PUFAs measured in blood components(red blood cells, serum, plasma)(OR=1.00, 95%CI:0.92-1.09, P=0.96)showed statistically significant associations with cancer risk. Subgroup analysis focusing on breast cancer revealed that in European and American regions, a higher ω-6/ω-3PUFAs ratio was associated with an increased risk of breast cancer incidence(OR=1.05, 95%CI:1.011.11, P=0.03), but this link was not statistically significant in non-European and American regions(OR=1.05, 95%CI:0.97-1.14, P=0.22). A higher dietary intake ratio of ω-6/ω-3PUFAs was correlated with an elevated risk of breast cancer incidence(OR=1.05, 95%CI:1.01-1.10, P=0.02), whereas the ratio of ω-6/ω-3PUFAs in blood(red blood cells, serum, plasma)did not show a statistically significant association with breast cancer risk(OR=1.07, 95%CI:0.93-1.23, P=0.37). Conclusion The influence of the ratio of ω-6/ω-3PUFAs on the risk of different tumors remains inconclusive. However, a higher ω-6/ω-3PUFAs ratio is associated with an increased risk of breast cancer, particularly in the European and American regions. In non-European and American regions, a higher ratio was found to significantly increase the risk of various types of tumor. Furthermore, a higher dietary ratio of ω-6/ω-3PUFAs intake is also associated with an increased risk of breast cancer development. These findings warrant further confirmation through additional prospective interventional studies.

Key words: ω-3 polyunsaturated fatty acids, ω-6/ω-3 polyunsaturated fatty acids ratio, Risk of carcinogenesis, Breast cancer, Meta-analysis