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

S. J. Weinstein, R. G. Ziegler, J. Selhub, T. R. Fears, H. D. Strickler, L. A. Brinton, R. F. Hamman, R. S. Levine, K. Mallin, P. D. Stolley

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalCancer Causes and Control
Issue number4
StatePublished - 2001


  • Cervix neoplasms
  • Homocysteine
  • Nutrition

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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