vitamin-b-12 and Uterine-Cervical-Dysplasia

In the process of progression to cancer from atypical squamous cells of undetermined significance (ASCUS), mostly Human Papilloma Virus (HPV) is responsible. Additionally, patients with cell cycle disorders are thought to be at risk. The aim of this prospective cohort trial was to analyze the association between presence of ASCUS and HPV persistence with folate and vitamin B12 levels. 200 patients who had Papanicolaou (PAP) smear test were divided into a ASCUS group (n:100) and control group (n:100). Control group consisted of women who did not have intraepithelial neoplasia, based on PAP smear results. HPV testing was also done in study group. Serum vitamin B12 and folate levels in ASCUS (+) HPV (+) patients were significantly lower than that of ASCUS (-) or ASCUS (+) HPV (-) patients (

Topics: Alphapapillomavirus; Atypical Squamous Cells of the Cervix; DNA, Viral; Female; Folic Acid; Humans; Papillomaviridae; Papillomavirus Infections; Prospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12

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.

Topics: Case-Control Studies; Contraceptives, Oral; Copper; Diet; Dietary Fats; Dietary Supplements; Erythrocytes; Ethnicity; Fatty Acids, Unsaturated; Female; Folic Acid; Homocysteine; Humans; Linear Models; Risk Factors; Uterine Cervical Dysplasia; Vitamin B 12

We performed the deoxyuridine suppression test (dUST) along with assessment of folate and vitamin B-12 status in blood specimens from 136 normal women and 109 women with cervical dysplasia. All tests were repeated at 2, 4, and 6 mo in subjects with dysplasia during a randomized, double-blind intervention trial in which 50 received a 10-mg daily oral folic acid supplement (F group) and 59 received a placebo (P group). Median folate concentration increased fivefold in plasma and threefold in erythrocytes of F group beginning at the second months and remained elevated whereas concentrations of the P group remained unchanged. Vitamin B-12 values did not vary significantly in either group. The dUST value decreased from 10.4 +/- 4.6% (means +/- SD) pretreatment to 4.5 +/- 4.7% in F group after 2 mo (p less than 0.001). The dUST values had significant negative correlation with plasma and erythrocyte folate concentrations. However, erythrocyte folate had the greatest power to distinguish P group from F group.

Topics: Adult; Deoxyuridine; DNA; Erythrocytes; Female; Folic Acid; Humans; Male; Middle Aged; Nutritional Status; Random Allocation; Thymidine; Uterine Cervical Dysplasia; Vitamin B 12

To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42-8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46-18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

Topics: Carbon; Female; Folic Acid; Humans; Papillomaviridae; Papillomavirus Infections; Polymorphism, Genetic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12

Diet and lifestyle play an important role in etiology of various tumors. Serum concentration of folate and vitamin B12may be associated with carcinogenesis since they are involved in DNA methylation and nucleotide synthesis. However, the role of these micronutrients on development of cervical cancer is still controversial. Thus, the aim of this study was to analyze the association of lower status of folate and vitamin B12 with the risk of pre-neoplastic cervical lesions.. Our sample group was divided in Control group (n = 120) - women with normal cytology, and Case groups (n = 57) - women presenting Atypical Squamous Cells of Undetermined Significance (ASC-US, n = 21), Low Grade Squamous Intraepithelial Lesion (LSIL; n = 16), and High-Grade lesions (n = 20). We obtained cervical samples for cytology analysis and HPV detection, and blood samples for evaluation of serum concentration of folate and vitamin B12.. No difference of serum folate was observed among Cases and Control groups. On the other hand, women with High-Grade lesions presented significant lower median concentration of vitamin B12 if compared to another groups. Then, we observed increased risk of High-Grade lesions among participants with low vitamin B12 levels was observed in relation to women that presented high levels of the micronutrient and from Control group [OR (95% CI): 2.09 (0.65-6.76), p = 0.216], ASC-US [OR (95% CI): 3.15 (0.82-12.08), p = 0.095], and LSIL [OR (95% CI): 3.10 (0.76-12.70), p = 0.116].. Low concentration of vitamin B12 was associated with an increased risk of High-Grade cervical lesions. Besides, we did not observe any difference of serum folate among women with normal cytology and women with pre-neoplastic cervical lesions.

Topics: Female; Folic Acid; Humans; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12

We previously reported that a higher degree of methylation of CpG sites in the promoter (positions 31, 37, 43, 52, and 58) and enhancer site 7862 of human papillomavirus (HPV) 16 was associated with a lower likelihood of being diagnosed with HPV 16-associated CIN 2+. The purpose of this study was to replicate our previous findings and, in addition, to evaluate the influence of plasma concentrations of folate and vitamin B12 on the degree of HPV 16 methylation (HPV 16m). The study included 315 HPV 16-positive women diagnosed with either CIN 2+ or ≤CIN 1. Pyrosequencing technology was used to quantify the degree of HPV 16m. We reproduced the previously reported inverse association between HPV 16m and risk of being diagnosed with CIN 2+. In addition, we observed that women with higher plasma folate and HPV 16m or those with higher plasma vitamin B12 and HPV 16m were 75% (P < 0.01) and 60% (P = 0.02) less likely to be diagnosed with CIN 2+, respectively. With a tertile increase in the plasma folate or vitamin B12, there was a 50% (P = 0.03) and 40% (P = 0.07) increase in the odds of having a higher degree of HPV 16m, respectively. This study provides initial evidence that methyl donor micronutrients, folate and vitamin B12, may play an important role in maintaining a desirably high degree of methylation at specific CpG sites in the HPV E6 promoter and enhancer that are associated with the likelihood of being diagnosed with CIN 2+.

Topics: Adult; Biopsy; CpG Islands; DNA Methylation; DNA, Viral; Enhancer Elements, Genetic; Female; Folic Acid; Genotype; Human papillomavirus 16; Humans; Male; Micronutrients; Middle Aged; Oncogene Proteins, Viral; Papillomavirus Infections; Promoter Regions, Genetic; Repressor Proteins; Risk Factors; Sequence Analysis, DNA; Uterine Cervical Dysplasia; Vitamin B 12; Young Adult

We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.. This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years).. Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels.. Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Topics: Adult; Aged; Case-Control Studies; Female; Folic Acid; Genetic Predisposition to Disease; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12; Young Adult

The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN ≥ 2).. This study included 376 women who tested positive for high-risk human papillomaviruses and were diagnosed with CIN ≥ 2 (cases) or CIN ≤ 1 (non-cases). CIN ≥ 2 (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥ 70% versus <70%) and CC LINE-1 methylation (≥ 54% versus <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.. Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN ≥ 2 (odds ratio 0.44, 95% confidence interval 0.24-0.83, P = 0.011), whereas there was no significant association between degree of CC LINE-1 methylation and CIN ≥ 2 (odds ratio 0.86, 95% confidence interval 0.51-1.46, P = 0.578). Among non-cases, women with supraphysiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared with women with lower folate and lower vitamin B12 (odds ratio 3.92, 95% confidence interval 1.06-14.52, P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.. These results suggest that a higher degree of LINE-1 methylation in PBMCs, a one-carbon nutrient-related epigenetic alteration, is associated with a lower risk of developing CIN.

Topics: Adult; Biomarkers; Carbon; Case-Control Studies; Cervix Uteri; Confidence Intervals; Deoxyribonuclease I; DNA Methylation; Epigenomics; Female; Folic Acid; Follow-Up Studies; Humans; Leukocytes, Mononuclear; Logistic Models; Methylation; Middle Aged; Odds Ratio; Papillomavirus Infections; Premenopause; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Surveys and Questionnaires; Uterine Cervical Dysplasia; Vitamin B 12; Vitamin B Complex; Young Adult

The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or 19.8 ng/mL) who also had sufficient plasma vitamin B12 (>or=200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of

Topics: Ascorbic Acid; Biopsy; Carotenoids; Female; Folic Acid; Follow-Up Studies; Food, Fortified; Humans; Premenopause; Prospective Studies; Risk; Tocopherols; Uterine Cervical Dysplasia; Vitamin A; Vitamin B 12

Human papillomavirus (HPV) infections are the cause of most, if not all, cervical cancers. Women consistently positive for oncogenic type HPV infections have a greater risk of developing cervical dysplasia compared with women transiently infected. HPV infection alone appears to be insufficient to produce disease, suggesting that other cofactors may be needed. Folate, vitamin B12, and homocysteine, through their role in DNA methylation, may be involved in cervical neoplasia.. This study examined the associations between HPV persistence and circulating folate, vitamin B12, and homocysteine levels among 91 low-income Hispanic women. Further, the relation of these nutrients to cervical pathology was evaluated. HPV status was determined at two visits approximately 3 mo apart.. Adjusted mean circulating concentrations of folate, vitamin B12, and homocysteine were not statistically different between women with two positive HPV tests, one positive test, or two negative HPV tests. No association was observed between tertiles of folate, vitamin B12, or homocysteine and HPV persistence risk. Further, adjusted mean levels of these nutrients were not statistically different between cytologic grades.. Results from this small study did not support a role for folate, vitamin B12, or homocysteine in HPV persistence or cervical dysplasia.

Topics: Adolescent; Adult; Cervix Uteri; DNA, Viral; Female; Folic Acid; Homocysteine; Humans; Nutritional Status; Papillomaviridae; Papillomavirus Infections; Tumor Virus Infections; Uterine Cervical Dysplasia; Vitamin B 12

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.. 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.. 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.. 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.

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