Diane Currie

Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk.

To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case‐control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC‐PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07–1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC‐PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC‐PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC‐PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95–2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC‐PAT+/+ insertion‐deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed.

Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk.

Highly penetrant, but rare, mutations in genes involved in double-strand break repair (i.e., BRCA1 and BRCA2 ) are associated with a risk for breast cancer of 40% to 65% by age 70 years ([1][1], [2][2]). Polymorphisms in other double-strand break repair genes are thought to contribute to the risk

Detection of cadmium exposure in rats by induction of lymphocyte metallothionein gene expression

The induction of metallothionein (MT) gene expression in lymphocytes of rats was determined in order to detect exposure in vivo to cadmium. Both acute and chronic CdCl2 exposures resulted in the induction of the MT-1 gene in lymphocytes as measured by standard RNA Northern blot analysis. Twenty-four hours following an ip injection of 3.4 mg/kg CdCl2, a ninefold increase in MT gene expression was observed in lymphocytes, as well as five- and sevenfold increases in liver and kidney, respectively. Oral exposure of rats to 1-100 ppm CdCl2 via drinking water resulted in an approximate twofold enhanced MT signal in lymphocytes after 6 wk, and a threefold increase after 13 wk of exposure to 100 ppm Cd. No increases in lymphocyte MT gene expression were observed after 3 wk of Cd exposure. Liver MT gene expression was substantially induced following chronic Cd exposure, while kidney was not, although this organ had a higher basal expression of the MT-1 gene. Analysis of tissue Cd burdens demonstrated a dose-response Cd accumulation in liver and kidney, but only kidney burdens increased substantially with prolonged Cd exposure. These results demonstrate the utility of lymphocyte gene expression assays to detect in vivo toxicant exposure, and thus their applicability as molecular biomarker assays for human exposure assessment.

Development and Use of a Simple DNA Test to Distinguish Larval Redhorse Species in the Oconee River, Georgia

Abstract The robust redhorse Moxostoma robustum is a rare catostomid species that was recently “rediscovered” in three Atlantic slope drainages in the southeastern United States, including the Oconee River, Georgia. Adult population size in the Oconee River is declining, and the population may be senescent due to recruitment failure. Evaluation of the environmental factors affecting the success of young life stages requires the ability to distinguish robust redhorse larvae from those of other redhorse species in the Oconee River. The use of morphological approaches, including size at collection date, have proven to be problematic in distinguishing larval robust redhorse from notchlip redhorse M. collapsum from the Oconee River. We developed a mitochondrial DNA (mtDNA) assay to distinguish between reference adults of these two redhorse species from the Oconee, Savannah, and Pee Dee rivers. This mtDNA assay was then applied to unknown larval redhorse collections from the Oconee River. In one collection, dis...

Introgression of Nuclear DNA (nDNA) Alleles of Stocked Atlantic Coast Striped Bass with the Last Remaining Native Gulf of Mexico Population

Abstract Since the 1960s, only the Apalachicola–Chattahoochee–Flint (ACF) river system has continually supported a naturally reproducing population of striped bass Morone saxatilis of Gulf of Mexico (Gulf) lineage. Striped bass fry and fingerlings of Atlantic ancestry (from the Santee– Cooper system) were introduced into the ACF from the late 1960s to 1977. Genotypes were previously identified that were unique to fish from the ACF and that confirmed the continued natural reproduction of striped bass of Gulf ancestry within that population. Also, no significant difference in haplotype frequencies between “pure” archived ACF and extant ACF samples was found at an Xba I mitochondrial DNA (mtDNA) restriction site that is diagnostic in distinguishing extant ACF from extant Atlantic specimens. This suggested that significant maternally mediated introgression of Atlantic mtDNA genomes has not occurred. However, because mtDNA is maternally inherited, the introgression of paternally derived nuclear DNA alleles int...

Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology

Background Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA. Methods We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women’s Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison. Results We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping. Conclusions Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies.