Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women

Objectives: To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer. Methods: A large case-control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls. Results: Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (> 6.31 μmol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable. Conclusions: Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B₁₂ and/or B₆ inadequacy, or genetic polymorphisms affecting one-carbon metabolism.