Sex- and Ethnic-Specific Associations of Serum Lipids with Risk of 12 Cancers: Findings from 506,381 Adults in Two Large Cohorts

The contribution of serum lipids to carcinogenesis, including their effects on inflammation and oxidative stress, remains debated due to inconsistent evidence across populations. This study aimed to elucidate sex- and ethnic-specific associations between serum lipid indices and the risk of 12 common cancers in two large, distinct populations. We conducted a pooled analysis of 506,381 participants from the UK Biobank (UKB) and the Korean Cancer Prevention Study-II (KCPS-II) cohort, with median follow-ups of 12.0 and 13.0 years, respectively. Multivariable-adjusted Cox hazards models were used to estimate hazard ratios (HRs) for the association between baseline lipids and cancer incidence. In the UKB, a one-standard deviation (1-SD) increase in HDL-C was associated with a decreased overall cancer risk (HR 0.982, 95% CI: 0.969-0.995); meanwhile, a 1-SD increase in LDL-C was associated with an increased risk (HR 1.021, 1.009-1.034); higher HDL-C was linked to an increased risk of cervical cancer (HR 1.167, 1.019-1.337) and prostate cancer (HR 1.025, 1.001-1.049). These associations were not significant in the KCPS-II. The association between serum lipids and cancer risk is substantially modified by sex and ethnicity, suggesting that universal lipid-based prevention strategies may be inappropriate and underscoring the need for population-specific research.