Estrogen receptor-α polymorphism in a Taiwanese clinical breast cancer population: a case–control study

INTRODUCTION: Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-α polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age–incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-α in either population is therefore of value in the clinical setting for that ethnic group. METHODS: A case–control study was conducted to establish a database of ER-α polymorphisms in a Taiwanese population in order to compare Western and Taiwanese (Asian) distributions and to evaluate ER-α polymorphism as an indicator of clinical outcome. The ER-α gene was scanned in a Taiwanese clinical breast cancer group (189 patients) and in healthy individuals (177 healthy control individuals). PCR single-strand conformation polymorphism technology was employed and real-time PCR melting curve analysis was performed. RESULTS: Three sites of silent single nucleotide polymorphism (SNPs) were found, as reported previously in Western studies, but at significantly different frequencies. Among the three SNPs, the frequency of allele 1 (TCT → TCC) in codon 10 was significantly lower in breast cancer patients (32.0%) than in control individuals (40.4%; P = 0.018). We found that allele 1 (ACG → ACA) in codon 594 was less common in breast cancer patients with a family history of breast cancer (5.9%) than in those without such a history (19.6%; P = 0.049). Individually, both allele 1 in codon 325 (CCC → CCG) and allele 1 in codon 594 exhibited a reverse association with the occurrence of lymph node metastasis. Furthermore, incorporation of both SNP markers further increased predictive accuracy. CONCLUSIONS: Our data suggest that ER-α polymorphisms are correlated with various aspects of breast cancer in Taiwan. ER-α genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting breast cancer lymph node metastasis

Transgenic Potatoes for Potato Cyst Nematode Control Can Replace Pesticide Use without Impact on Soil Quality

Current and future global crop yields depend upon soil quality to which soil organisms make an important contribution. The European Union seeks to protect European soils and their biodiversity for instance by amending its Directive on pesticide usage. This poses a challenge for control of Globodera pallida (a potato cyst nematode) for which both natural resistance and rotational control are inadequate. One approach of high potential is transgenically based resistance. This work demonstrates the potential in the field of a new transgenic trait for control of G. pallida that suppresses root invasion. It also investigates its impact and that of a second transgenic trait on the non-target soil nematode community. We establish that a peptide that disrupts chemoreception of nematodes without a lethal effect provides resistance to G. pallida in both a containment and a field trial when precisely targeted under control of a root tip-specific promoter. In addition we combine DNA barcoding and quantitative PCR to recognise nematode genera from soil samples without microscope-based observation and use the method for nematode faunal analysis. This approach establishes that the peptide and a cysteine proteinase inhibitor that offer distinct bases for transgenic plant resistance to G. pallida do so without impact on the non-target nematode soil community

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility