Germline mutations in RAD51D confer susceptibility to ovarian cancer.

Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.

CYP2D6 gene variants and their association with breast cancer susceptibility.

Background: The gene encoding the phase I enzyme cytochrome P4502D6 (CYP2D6) has been previously investigated for its potential predictive role in the efficacy of breast cancer treatments such as tamoxifen, but its role in breast cancer susceptibility is unclear. This study aims to evaluate the association between germ line variations in CYP2D6 and breast cancer susceptibility.

Methods: DNA samples from 13,472 cases and controls were genotyped for seven known functional variants [minor allele frequency (MAF) ≥ 0.

CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen.

Introduction: Tamoxifen is one of the most effective adjuvant breast cancer therapies available. Its metabolism involves the phase I enzyme, cytochrome P4502D6 (CYP2D6), encoded by the highly polymorphic CYP2D6 gene. CYP2D6 variants resulting in poor metabolism of tamoxifen are hypothesised to reduce its efficacy.

Fine scale mapping of the breast cancer 16q12 locus.

Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5' end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants.

Hyaluronan-mediated motility receptor gene single nucleotide polymorphisms and risk of breast cancer.

A recent study used a network modeling strategy to generate a set of genes linked by potential functional associations. The hyaluronan-mediated motility receptor (HMMR) gene was identified as being as functionally associated with BRCA1 and thus a candidate breast cancer gene. SNPs rs10515860, rs299290, and rs7712023 were reported to be significantly associated with breast cancer in a joint analysis of two small case-control studies.

Identification of common variants in the SHBG gene affecting sex hormone-binding globulin levels and breast cancer risk in postmenopausal women.

Background: Circulating levels of sex hormone-binding globulin (SHBG) are inversely associated with breast cancer risk in postmenopausal women. Three polymorphisms within the SHBG gene have been reported to affect SHBG levels, but there has been no systematic attempt to identify other such variants.

Methods: We looked for associations between SHBG levels in 1,134 healthy, postmenopausal women and 11 tagging single nucleotide polymorphisms (SNP) in or around the SHBG gene.

Genome-wide scan for premature hypertension supports linkage to chromosome 2 in a large Kyrgyz family.

We report a genome-wide scan for susceptibility loci to hypertension in a single Kyrgyz family where 10 of the affected relatives developed hypertension before the age of 35 years, and some members have suffered stroke. The early onset of disease and the geographic isolation of the Kyrgyz population are both expected to select for an increased influence of genetic factors in hypertension. We genotyped 44 individuals from this Krygyz family with 374 microsatellite markers, covering a 10-centimorgan map.

Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype.

Previous studies have suggested a genetic component in susceptibility to hypoxia-induced pulmonary hypertension. We therefore estimated the prevalence of high-altitude pulmonary hypertension (HAPH) in a Kyrgyz population and whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene associates with HAPH. An electrocardiographic survey of 741 highlanders demonstrated electrocardiogram signs of cor pulmonale in 14% of subjects.

Detection of abundantly transcribed genes and gene translocation in human immunodeficiency virus-associated non-Hodgkin's lymphoma.

Several novel, differentially transcribed genes were identified in one centroblastic and one immunoblastic HIV-associated B-cell non-Hodgkin's lymphoma (B-NHL) by subtractive cloning. In both lymphomas, we detected an upregulated transcription of several mitochondrial genes. In the centroblastic B-NHL, we found a high level transcription of nuclear genes including the interferon-inducible gene (INF-ind), the immunoglobulin light chain gene (IgL), the set oncogene, and several unknown genes.

[Amplification of transcription of separate mitochondrial genes in human and monkey B-cell non-Hodgkin's lymphoma].

Mitochondrial genes that are overexpressed in human and monkey B-cell non-Hodgkin lymphomas (B-NHLs) were sought via subtraction hybridization, cloning, and differential screening of the resulting cDNA libraries. The cDNAs of mitochondrial genes made an appreciable proportion of all lymphoma-specific cDNAs. Lymphomogenesis was associated with overexpression of a mitochondrial gene set which varied with lymphoma type and always included NADHIV.

[Probable nature of Rickettsia prowazekii virulence].

A 29.5 kda outer membrane protein (OmpB) of R. prowazekii virulent Breinl strain is known to differ from its counterpart in attenuated Madrid E strain, while OmpB of this latter one and of its virulent variant EVir coincide in mobility.