Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as markers of cervical dysplasia

Cancer. 2000 Jul 15;89(2):376-82. doi: 10.1002/1097-0142(20000715)89:2<376::aid-cncr24>;2-o.


Background: An association between B-complex vitamins and related compounds with the development of cervical neoplasia is biologically plausible, yet to the authors' knowledge epidemiologic investigations of these potential biomarkers are limited.

Methods: A case-control study was designed to examine the relation between plasma folate, homocysteine, vitamin B(12), and cysteine and early, premalignant changes in cervical epithelial cells among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated cervical cells for human papillomavirus DNA testing by polymerase chain reaction, and a personal interview were obtained from 185 women with atypical squamous cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous intraepithelial lesions (SIL), and 191 women with cytologically normal (Papanicolaou) smears.

Results: Age-adjusted and ethnicity-adjusted mean plasma concentrations of cysteine, but not other nutrients, were significantly lower among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive trend in the odds ratio for SIL but not ASCUS was found for increased plasma homocysteine concentrations, but this finding was not statistically significant. High plasma levels of cysteine were associated with a reduced risk of ASCUS (P value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2-0.7) for the highest compared with the lowest quartile of cysteine concentration. A weak, negative relation between cysteine and the development of low grade SIL (LSIL) but not high grade SIL (HSIL) also was found.

Conclusions: The results of the current study do not support the hypothesis that folate, homocysteine, or B(12) are markers of cervical dysplasia risk. A possible inverse association between plasma cysteine concentrations and the risk of cervical dysplasia needs further study.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alcohol Drinking
  • Case-Control Studies
  • Contraceptives, Oral
  • Cysteine / blood*
  • DNA, Viral / analysis
  • Female
  • Folic Acid / blood*
  • Gravidity
  • Homocysteine / blood*
  • Humans
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomavirus Infections
  • Regression Analysis
  • Risk Factors
  • Tumor Virus Infections
  • Uterine Cervical Dysplasia / blood*
  • Vitamin B 12 / blood*


  • Contraceptives, Oral
  • DNA, Viral
  • Homocysteine
  • Folic Acid
  • Cysteine
  • Vitamin B 12