Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3

Henao, Olga; Piyathilake, Chandrika J.; Waterbor, John W.; Funkhouser, Ellen; Johanning, Gary L.; Heimburger, Douglas C.; Partridge, Edward E.

doi:10.1002/ijc.20695

Cited by 33 publications

(29 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The genotyping rates in the present study were also very high for each locus, and the haplotype analysis provided a better basis for evaluating the interaction between genetic polymorphisms and cervical carcinogenesis risk. Prior studies of the MTHFR haplotype and cervical cancer were limited to only two candidate polymorphisms (C655T and A1298C) [14,32]. In the present study, Hap3 showed a significant association with CIN1.…”

Section: Discussionmentioning

confidence: 43%

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

Tong

Lee

Song

et al. 2009

Cancer Causes Control

View full text Add to dashboard Cite

The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 casecontrol samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

show abstract

Section: Discussionmentioning

confidence: 43%

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

Tong

Lee

Song

et al. 2009

Cancer Causes Control

View full text Add to dashboard Cite

show abstract

“…Using the validated FFQ, a high prevalence of folate intake inadequacy has been shown along with an increase in mutated MTHFR C677T polymorphism that may modulate the risk of cancer according to folate status (Henao et al, 2005;Piyathilake et al, 2007;Flatley et al, 2009). According to our study, healthy young women may have higher folate needs due to the increased prevalence of the T allele and reduced folate intake compared with older groups.…”

Section: Discussionmentioning

confidence: 99%

“…However, some studies have supported the existence of gene-folate status interactions in the etiology of cervical cancer, and specifically it has been reported that MTHFR T allele and reduced dietary folate may increase the risk for cervical squamous intraephitelial lesions (Goodman et al, 2001), while, on the contrary, a study conducted after folic acid fortification reported that MTHFR polymorphism is associated with reduced risk of CIN 2 or 3 (Henao et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

et al. 2011

View full text Add to dashboard Cite

Background/Objectives: Folate has been recognized to ensure reproductive health and there is a growing body of epidemiological evidence suggesting that the methylenetetrahydrofolate reductase (MTHFR) 677T allele and reduced dietary folate may increase the risk of cervical cancer. The main focus of our survey was to investigate the distribution of the MTHFR C677T polymorphism in relation to women's year of birth and to assess their folate intake and folic acid supplementation. Subjects/Methods: During a 6-months period, 307 healthy women of childbearing age in Catania, Italy, were enrolled in the cross-sectional study. Folate intake was estimated by a semiquantitative food frequency questionnaire and DNA extracted from blood samples for MTHFR C677T genotyping. Results: A TT genotype frequency of 20.5% with an increase in the prevalence of the TT genotype in the cohort of women born since 1959 was shown. The prevalence of inadequate folate intake was 51.5%, significantly higher in non-pregnant women (83.4%) than in pregnant ones (12.3%) with a decrease during the three trimesters of pregnancy (from 25.7 to 5.0%; P ¼ 0.013). The use of folic acid supplements improved during the three trimester of pregnancy (from 71.4 to 95.0%; P ¼ 0.001).Conclusions: Healthy young women may have higher folate needs due to increasing prevalence of the T allele and reduced folate intake compared with older groups. However, clinicians should be cautious when recommending supplements to women in late pregnancy due to the possible implications in the pregnancy outcome.

show abstract

“…A detailed description of the study design has been recently published (10). Briefly, the subjects of this study were a subset of women recruited for the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study (ALTS) at the clinical center in Birmingham, AL, who agreed to participate in an ancillary study of gene-nutrient interactions and risk of developing CIN 2 and 3.…”

Section: Methodsmentioning

confidence: 99%

“…The colorectal cancer studies suggested that the MTHFR polymorphism reduces colon cancer risk, perhaps by increasing 5, 10 methylenetetrahydrofolate levels for DNA synthesis, but that low folate intake or high alcohol intake may negate some of the protective effect. In a study conducted after folate fortification was implemented in the USA, we reported that MTHFR polymorphism is associated with reduced risk of cervical intraepithelial neoplasia (CIN) 2 or 3 (10). This protective effect is also likely to be due to a shift in the folate pathway toward DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status

Piyathilake¹,

Azrad²,

Macaluso³

et al. 2007

Nutrition

Self Cite

View full text Add to dashboard Cite

Objectives-We previously reported that women polymorphic for the methylenetetrahydrofolate reductase (MTHFR) gene were less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3 (odds ratio [OR] = 0.40, 95 % confidence interval [CI]: 0.21, 0.78, p=0.007). In the current study, we tested whether this protective association is modified by the circulating riboflavin status in the same study population.Methods-Riboflavin status was assessed by the erythrocyte glutathione reductase (EGR) assay and expressed in terms of an EGR activity coefficient (EGRAC). The status of MTHFR polymorphism, riboflavin, and circulating concentrations of folate, vitamins B-12, A, E, C and total carotene were ascertained in 170 White and 265 African-American women positive for the cervical presence of high-risk human papilloma virus (HR-HPV). Presence/absence of CIN 2 or 3 was determined histologically, and associations with risk factors were examined using multiple logistic regression. Eighty women with CIN 2 or 3 lesions were compared to 355 women without cervical lesions. Based on the median EGRAC of 1.4, women were grouped into low (> 1.4) and high (≤1.4) riboflavin status.Results-Women with MTHFR polymorphism and low riboflavin status were significantly less likely to have CIN 2 or 3 than the referent group of women without the polymorphism and high riboflavin status (OR = 0.35, 95% CI: 0.13, 0.92, p= 0.034). MTHFR polymorphism was not associated with CIN 2 or 3 in women with high riboflavin status (OR = 0.51, 95% CI: 0.22, 1.19, p = 0.119), nor were any of the associations influenced by folate levels.Conclusions-A further inactivation of polymorphic MTHFR by low riboflavin status and a resulting shift in the folate metabolic pathway toward DNA synthesis may explain these observations. The practical implications of this complex gene-nutrient-disease interaction will require further investigation.

show abstract

Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3

Cited by 33 publications

References 49 publications

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status

Contact Info

Product

Resources

About