Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women.
OBJECTIVE
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 micromol/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.
Weinstein
S J
SJ
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Ziegler
R G
RG
Selhub
J
J
Fears
T R
TR
Strickler
H D
HD
Brinton
L A
LA
Hamman
R F
RF
Levine
R S
RS
Mallin
K
K
Stolley
P D
PD
D000328:Adult; D000407:Alabama; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003120:Colorado; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005431:Florida; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007087:Illinois; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D010414:Pennsylvania; D011237:Predictive Value of Tests; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
D006710:Homocysteine; D025101:Vitamin B 6; D014805:Vitamin B 12