We concluded that GHb is a better predictor of CVD and IHD mortality than FPG or PCPG in women without diabetes; no single measure of glycemia was predictive in men. The reason for the sex difference is unexplained.

Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 onecarbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) 5 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend 5 0.01, false discovery rate 5 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Metaanalyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk. ' 2007 Wiley-Liss, Inc.Key words: folate metabolism; single nucleotide polymorphism; breast cancer Alterations in the one-carbon metabolism pathway can influence DNA methylation, synthesis and repair, which play a critical role in carcinogenesis. Dietary factors involved in this pathway include folate and methionine which can influence the supply of methyl groups, other B-vitamins (B2, B6 and B12) which are cofactors for enzymes in this pathway, and vitamin B12 and alcohol intake which can modify the biological response to inadequate dietary folate. 1 Some, although not all, epidemiological studies have found an inverse association between breast cancer risk and folate intake, 2 with weaker evidence for other B-vitamins. [3][4][5][6] Polymorphisms in critical enzymes involved in one-carbon metabolism could also influence the risk of cancer in conjunction with folate and methionine intake, as well as other B-vitamins. Most epidemiological studies of breast cancer have focused on 2 putative functional polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A) involved in the conversion of N 5 ,N 10 -methylenetetrahydrofolate to 5-methyltetrahydrofolate, the major circulating form of folate; however, findings are inconclusive. 5-14 A recently published meta-analysis of studies showed no evidence for an association between MTHFR A222V and breast cancer risk in postmenopausal women; however, it suggested an association in premenopausal women. 15 Studies have also suggested an interaction between folate and variants of MTHFR. 5,6,8,13 Variation in other genes in the one-...

The nuclear genes PET117 and PET191 are required for the assembly of active cytochrome c oxidase in S. cerevisiae, yet their gene products are not subunits of the final assembled cytochrome c oxidase complex. Plasmids bearing PET117 or PET191 were isolated by their ability to complement the pet117-1 or pet191-1 mutations, respectively. By restriction mapping, subcloning, and deletion analysis of yeast DNA fragments that complement these mutations, the PET117 and PET191 genes were localized to smaller regions of DNA, which were then sequenced from both strands. The PET117 open reading frame is of 107 codons and the PET191 open reading frame is of 108 codons. Neither the PET191 nor PET117 DNA sequences have been reported previously, and the derived amino-acid sequences of the PET191 and PET117 open reading frames exhibit no significant primary amino-acid sequence similarity to other protein sequences available in the NBRF data base, or from translated Genbank sequences. By hybridization of PET117 or PET191 probes first to a chromosome blot and next to a library of physically mapped fragments of yeast genomic DNA, the map locations of the PET191 and PET117 genes were determined. PET117 is located on chromosome V near the HIS1 gene and PET191 is located on chromosome X near the CYC1 gene.

Objective. Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. Methods. Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. Results. At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10−9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10−9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10−8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10−7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10−7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10−7). Conclusion. While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.