;;;

The previously reported association of the APEX Asp148Glu single nucleotide polymorphism (SNP) with cancer, and the suggestion of associations of the XRCC3 Thr241Met and hOGG1 Ser326Cys SNP sites with G(2) chromosomal radiosensitivity were investigated in a new study of 30 childhood and young adult cancer survivors, their 30 partners, and 55 offspring. An additional SNP, hOGG1 Arg46Gln was also analyzed. Data on G(2) chromosomal radiosensitivity was available on 29of the families including 53 offspring. No significant associations of genotype with cancer or G(2) chromosomal radiosensitivity were observed.

BACKGROUND: Toll-like receptor (TLR) polymorphisms have been associated with atopic diseases in children and adults. Development of atopic diseases may be modified by TLR-mediated signals that modulate T-regulatory cells (Tregs) early in life when maternal influences are still present and relevant. The aim of thisstudy was to assess whether genetic TLR variants influence Tregs in neonates. METHODS: Twelve single nucleotide polymorphisms located in TLR1, TLR2, TLR4, TLR6, and TLR10 were genotyped in 200 cord blood samples (72 samples from atopic, 128 from nonatopic mothers). Cord blood mononuclear cells were cultured without or with stimulation [lipid A (LpA), peptidoglycan (Ppg), phytohemagglutinin, house dust mite]. mRNA expression of Treg marker genes [forkhead box protein P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte activation gene 3 (LAG3)], TLR2, Th1/Th2 cytokines, and tumor necrosis factor alpha (TNF-alpha) was measured. RESULTS: In children with the AA genotype of theTLR2 promoter variant rs4696480, gene expression of FOXP3 and Treg marker genes GITR and LAG3 as well as Th2 cytokines and TNF-alpha secretion was significantlyincreased in the presence of maternal atopy and Tregs decreased without maternalatopy. In carriers of the GG genotype for TLR2 rs1898830, gene expression of Treg marker genes was significantly decreased with and increased without maternal atopy. FOXP3 expression was also modified by TLR1 rs4833095 (P expression in cord blood. Gene-immunological interactions of the TLR pathway influence Tregs early in life, modulated by maternal atopy. This may be relevant for immune maturationin the development of atopic diseases in childhood.#CI- (c) 2011 John Wiley & Sons A/S.