Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin.

BACKGROUND: Knowledge of the characteristics and effective use of tumour markers for mesothelioma is essential for early-stage diagnosis of mesothelioma. We examined whether renal dysfunction influences blood concentrations of promising new tumour markers, N-ERC/mesothelin (N-ERC) and osteopontin (OPN), to an important degree. PATIENTS AND METHODS: Levels of serum N-ERC and plasma OPN in 32 patients with chronic renal dysfunction, 22 of whom were on hemodialysis (CKD group), and 102 healthy volunteers were measured. RESULTS: Serum concentrations of N-ERC and plasma concentrations of OPN in the CKD group were significantly higher than those in volunteers, regardless of diabetes status and age. Blood concentrations of these markers increased as renal function decreased. CONCLUSION: N-ERC and OPN concentrations are significantly influenced by renal function. Therefore, the extent of renal failure must be considered when inferring the existence of tumours and chemotherapeutic response from the values of these markers in routine practice.

Linkage disequilibrium grouping of single nucleotide polymorphisms (SNPs) reflecting haplotype phylogeny for efficient selection of tag SNPs.

Single nucleotide polymorphisms (SNPs) have been proposed to be grouped into haplotype blocks harboring a limited number of haplotypes. Within each block, the portion of haplotypes is expected to be tagged by a selected subset of SNPs; however, none of the proposed selection algorithms have been definitive. To address this issue, we developed a tag SNP selection algorithm based on grouping of SNPs by the linkage disequilibrium (LD) coefficient r(2) and examined five genes in three ethnic populations--the Japanese, African Americans, and Caucasians. Additionally, we investigated ethnic diversity by characterizing 979 SNPs distributed throughout the genome. Our algorithm could spare 60% of SNPs required for genotyping and limit the imprecision in allele-frequency estimation of nontag SNPs to 2% on average. We discovered the presence of a mosaic pattern of LD plots within a conventionally inferred haplotype block. This emerged because multiple groups of SNPs with strong intragroup LD were mingled in their physical positions. The pattern of LD plots showed some similarity, but the details of tag SNPs were not entirely concordant among three populations. Consequently, our algorithm utilizing LD grouping allows selection of a more faithful set of tag SNPs than do previous algorithms utilizing haplotype blocks.