Correlates of total plasma homocysteine: folic acid, copper, and cervical dysplasia.

We examined correlates of total plasma homocysteine (tHcy) in 294 subjects with cervical intraepithelial neoplasia and 170 control subjects. Associations of tHcy with risk factors for cervical intraepithelial neoplasia and 24-h intakes and biochemical indices of nutrients were examined. Plasma and red blood cell folate and plasma B(12) were strong inverse correlates of tHcy (r = -0.35, -0. 31, and -0.27, respectively). Plasma copper and severity of dysplasia were positively correlated with tHcy (r = 0.14 and 0.21, respectively). A stepwise regression model that included red blood cell folate, plasma copper, grade of dysplasia, ethnicity, intake of polyunsaturated fatty acids, plasma vitamin B(12), intake of fat, and oral contraceptive use explained 29% of the variation in tHcy. Two hundred thirty-five subjects with cervical intraepithelial neoplasia were randomized to receive folic acid (10 mg/d) or placebo for 6 mo. After 2, 4, and 6 mo, mean tHcy in the folate-supplemented group (7.2 +/- 1.8, 7.0 +/- 1.9, and 7.0 +/- 2.3 micromol/L, respectively) was significantly lower than baseline and the placebo group at 2, 4, and 6 mo (8.9 +/- 3.1, 8.4 +/- 3.0, and 8.9 +/- 3.1 micromol/L, respectively). Supplementation lowered tHcy even in subjects in the highest quintile of baseline folate. Folate, vitamin B(12), copper, and severity of dysplasia are associated with tHcy. Folate supplementation significantly lowers tHcy even in folate-replete subjects.

Effect of total plasma homocysteine on cervical dysplasia risk.

We investigated whether total plasma homocysteine (tHcy) is associated with risk for cervical intraepithelial neoplasia (CIN). tHcy was evaluated, along with numerous risk factors for CIN and biochemical indexes of nutrients, in a previously reported study population of 294 subjects with CIN and 170 female controls without CIN. tHcy was significantly higher in cases than in controls (9.1 vs. 8.3 mumol/l, p = 0.002). Human papillomavirus type 16 infection [odds ratio (OR) = 6.7], oral contraceptive use (OR = 6.0), parity (OR = 2.2), and cigarette smoking (OR = 1.9) were significantly associated with CIN after adjustment for each other and for age, number of sexual partners, and plasma tHcy, folate, iron, and zinc. Human papillomavirus type 16 positivity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.7) than when it was < or = 9.12 mumol/l (OR = 3.0). Cigarette use increased risk for CIN when tHcy was > 9.12 mumol/l (OR = 3.9), but not when tHcy was < or = 9.12 mumol/l (OR = 1.5). Parity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.0) than when tHcy was < or = 9.12 mumol/l (OR = 2.0). These results suggest that elevated plasma tHcy is a risk factor for cervical dysplasia and that it enhances the effects of other risk factors. It is unknown whether tHcy is serving as a marker of folate deficiency or is acting through other mechanisms.