Mammalian cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) form a supergene family consisting of four distinct families, named alpha, mu, pi and theta. In humans one member of the mu class gene family (GSTM1) has been shown to be polymorphic and is only expressed in 55-60% of individuals. Previous studies have shown a possible link with the null phenotype and susceptibility to cancer, in particular to lung cancer. In this study we genotyped individuals with breast, bladder and colorectal cancer. A total of 490 individuals with cancer were studied, and consisted of 97 bladder, 197 breast and 196 colorectal cancers. No significant differences were observed in the frequency of nulled individuals in bladder or breast cancer patients when compared with a control population of 225 individuals. However, a significant excess of nulled individuals were seen in colorectal cancer: 56.1% compared with the control group value of 41.8%. This was shown to be highly significant depending on the site of the tumours and > 70% of individuals with a tumour in the proximal colon were GSTM1 nulled. This is an approximately 2-fold increase in colon cancer risk in these individuals.

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The human genome contains a large number of interspersed simple repeat sequences that are variable in length and can therefore serve as highly informative, polymorphic markers. Typing procedures include conventional multilocus and single locus probing, and polymerase chain reaction aided analysis. We have identified simple sequences in a cosmid clone stemming from the human Y chromosome and consisting of (gata)n repeats. We have compared these with two equivalent simple repeat loci from chromosome 12. After amplifying the tandemly repeated motifs, we detected between four and eight different alleles at each of the three loci. Codominant inheritance of the alleles was established in family studies and the informativity of the simple repeat loci was determined by typing unrelated individuals. The polymorphisms are suitable for application in linkage studies, practical forensic case work, deficiency cases in paternity determination, and for studying ethnological questions. The mutational mechanisms that bring about changes in simple repeats located both on the autosomes and on the sex chromosomes, are discussed.

Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.

In mammals, the cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) are a supergene family comprised of four multigene families, named alpha, mu, pi and theta. In man, within the mu class gene family there is a gene (the GSTmu 1 locus) that is polymorphic and is only expressed in 50-55% of individuals. It has previously been reported, using trans-stilbene oxide (tSBO) as a specific substrate for the expressed phenotype, that smokers with the null phenotype had a greater susceptibility to lung cancer. In a subsequent study, it was shown that on Southern blot analyses of human DNAs using a GSTmu 1 cDNA probe a DNA fragment was absent in certain individuals. The absence of this band correlated with the tSBO null phenotype. In the present work, DNA clones derived from GST mu class genomic sequences were used as probes in Southern blot analyses and confirmed the correlation between the lack of a DNA fragment and the null phenotype; moreover in this case, using radioimmunoassay for the GST mu protein, these probes were then used in a genotyping assay to investigate further the association of GSTmu 1 polymorphism with susceptibility to lung cancer. It was found that in a control group of 225 individuals, of unknown smoking history, 42% lacked the restriction fragment and were homozygous null, and therefore 58% were either heterozygous or were homozygous normal. Among 228 lung cancer patients, which included all tumour types, a similar distribution occurred, namely 43% were homozygous and 57% were heterozygous or homozygous normal. If, however, the tumours were analysed by tumour type a small but significant positive correlation with the homozygous null genotype was seen in squamous carcinoma of the lung, and an apparently negative correlation with adenocarcinoma of the lung.