Serum folate and homocysteine levels in head and neck squamous cell carcinoma

Abstract

We have studied the relationship between diabetes‐associated autoantibodies and various HLA genotypes and alleles in patients with newly diagnosed type 1 diabetes, in non‐diabetic siblings and in children representing the general population to test the hypothesis that specific HLA genes regulate the humoral immune response to various autoantigens. Among the newly diagnosed patients we observed that those carrying the DR4‐DQB1*0302 haplotype had increased levels of insulin autoantibodies (IAA) and IA‐2 antibodies (IA‐2A), but low levels of GAD antibodies (GADA). In contrast, those with the DR3‐DQB1*02 haplotype had increased GADA titers but low IAA and IA‐2 levels. DQB1*02‐homozygous patients had a conspicuously low frequency and low levels of IA‐2A. Among the siblings there was an apparent association between genetic risk and the prevalence of islet cell antibodies (ICA), IAA, GADA, IA‐2A and multiple autoantibodies, the latter being detectable at a frequency of 24.1% in high risk siblings and at a frequency of only 0.9% in those with genotypes conferring disease protection. Among 7–16‐year‐old Finnish schoolchildren there was an association between GADA and the DQB1*02/*0302 genotype and the DQB1*0302 allele. Among young children identified from the general population based on high (DQB1*02/0302 heterozygosity) or moderate (DQB1*0302/x; x ≠ *02, *0301, *0602, *0603) genetic risk for type 1 diabetes the high risk children seroconverted more often to positivity for ICA, GADA and IA‐2A over their first 2 years of life. Among older sibs of these children we observed an obvious relationship between the degree of genetic risk and the frequency of ICA, IAA, GADA, IA‐2A, and multiple antibodies. Taken together these observations suggest that HLA genes have a strong impact on the appearance of diabetes‐associated autoantibodies both in first‐degree relatives of affected children and in the general population. In patients with newly diagnosed disease IA‐2A may be a more specific marker of beta‐cell damage, whereas GADA might reflect a propensity to autoimmunity in general. © 2002 Wiley‐Liss, Inc.

Methylenetetrahydrofolate reductase polymorphisms and risk of squamous cell carcinoma of the head and neck: A case‐control analysis

“…However, when we evaluated these 3 polymorphisms together based on their reported linkage disequilibrium, 39 the risk of SCCHN increased as the number of risk alleles increased in a dose-dependent manner. These findings are biologically plausible given that patients with SCCHN tend to have a lower serum level of folate than cancer-free controls, 6 the MTHFR gene plays a key role in folate metabolism and these 3 polymorphisms cause amino acid changes in the MTHFR gene. To the best of our knowledge, no reported study has simultaneously investigated the associations between these 3 MTHFR polymorphisms and risk of SCCHN.…”

“…3 For example, low dietary intake of fruits and vegetables was found to be associated with risk of SCCHN, 4,5 which was supported by the presence of lower serum levels of folate but higher serum levels of homocysteine in SCCHN patients than in cancer-free controls. 6 Folate is one of the constituents of vegetables and fruits that may provide protection against cancer 7,8 and provides methyl groups required for intracellular methylation reactions, including formation of homocysteine. Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, catalyzes folate metabolic transformation to 5-methyltetrahydrofolate that converts methionine to S-adenosylmethionine, which is the universal methyl donor for many intracellular methylation reactions, especially for DNA methylation.…”

Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case–control study

“…Thus, further study of the folate-NPC association in high-risk Chinese adults is necessary. In addition, only a few studies of limited numbers of NPC cases have assessed the effects of vitamin B 6 (16,19,20) , B 12 (23)(24)(25)27) and methionine (28) on the risk for head and neck cancer, and their results have been inconsistent.…”

Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma

“…5 Human papillomavirus (HPV) infection and low dietary folate have also been implicated in the etiology of this disease. [6][7][8][9] The WNT signaling pathway, activated through the binding of WNT proteins to the membrane-bound Frizzled receptors, leads to the stabilization and increase in the levels of the transcription factor b-catenin protein. This, in turn, leads to the activation of an array of target genes involved in numerous cellular processes important in tumor development, such as cell growth and survival, intercellular adhesion and cellular morphogenesis.…”