Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

<p>Abstract</p> <p>Background</p> <p>The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (<it>Sipa1</it>) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing <it>Sipa1 </it>cell line developing 1.5 to 2 fold more surface pulmonary metastases. <it>Sipa1 </it>encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline <it>SIPA1 </it>SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that <it>SIPA1 </it>may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of <it>SIPA1 </it>and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia.</p> <p>Methods</p> <p>The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program.</p> <p>Results</p> <p>Results indicated significance with <it>SIPA1 </it>SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence.</p> <p>Conclusion</p> <p>This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of <it>SIPA1 </it>in breast tumourgenesis. <it>SIPA1 </it>SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A)), did not show significant associations with breast cancer incidence, yet were associated with lymph node metastasis in the previous study. This suggests that <it>SIPA1 </it>may be involved in different stages of breast carcinogenesis and since this study replicates a previous study of the associated SNP, it implicates variants of the <it>SIPA1 </it>gene as playing a potential role in breast cancer.</p

Measuring the effectiveness of management interventions at regional scales by integrating ecological monitoring and modelling

Background: Because of site‐specific effects and outcomes, it is often difficult to know whether a management strategy for the control of pests has worked or not. Population dynamics of pests are typically spatially and temporally variable. Moreover, interventions at the scale of individual fields or farms are essentially unreplicated experiments; a decrease in a target population following management cannot safely be interpreted as success because, for example, it might simply be a poor year for that species. Here, we argue that if large‐scale data are available, population models can be used to measure outcomes against the prevailing mean and variance. We apply this approach to the problem of rotational management of the weed Alopecurus myosuroides. Results: We derived density‐structured population models for a set of fields that were not subject to rotational management (continuous winter wheat) and another group that were (rotated into spring barley to control A. myosuroides). We used these models to construct means and variances of the outcomes of management for given starting conditions, and to conduct transient growth analysis. We show that, overall, this management strategy is successful in reducing densities of weeds, albeit with considerable variance. However, we also show that one variant (rotation to spring barley along with variable sowing) shows little evidence for additional control. Conclusion: Our results suggest that rotational strategies can be effective in the control of this weed, but also that strategies require careful evaluation against a background of spatiotemporal variation

Evaluating the potential of Unmanned Aerial Systems for mapping weeds at field scales: A case study with Alopecurus myosuroides

Summary: Mapping weed densities within crops has conventionally been achieved either by detailed ecological monitoring or by field walking, both of which are time-consuming and expensive. Recent advances have resulted in increased interest in using Unmanned Aerial Systems (UAS) to map fields, aiming to reduce labour costs and increase the spatial extent of coverage. However, adoption of this technology ideally requires that mapping can be undertaken automatically and without the need for extensive ground-truthing. This approach has not been validated at large scale using UAS-derived imagery in combination with extensive ground-truth data. We tested the capability of UAS for mapping a grass weed, Alopecurus myosuroides, in wheat crops. We addressed two questions: (i) can imagery accurately measure densities of weeds within fields and (ii) can aerial imagery of a field be used to estimate the densities of weeds based on statistical models developed in other locations? We recorded aerial imagery from 26 fields using a UAS. Images were generated using both RGB and R mod (R mod 670-750 nm) spectral bands. Ground-truth data on weed densities were collected simultaneously with the aerial imagery. We combined these data to produce statistical models that (i) correlated ground-truth weed densities with image intensity and (ii) forecast weed densities in other fields. We show that weed densities correlated with image intensity, particularly R mod image data. However, results were mixed in terms of out of sample prediction from field-to-field. We highlight the difficulties with transferring models and we discuss the challenges for automated weed mapping using UAS technology

The population dynamics of weeds in winter wheat

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The impact of future socio-economic and climate changes on agricultural land use and the wider environment in East Anglia and North West England using a metamodel system

This paper describes a procedure to use a model interactively to investigate future land use by studying a wide range of scenarios defining climate, technological and socio-economic changes. A full model run of several hours has been replaced by a metamodel version which takes a few seconds, and provides the user with an immediate visual output and with the ability to examine easily which factors have the greatest effect. The Regional Impact Simulator combines a model of agricultural land use choices linked with models of urban growth, flooding risk, water quality and consequences for wildlife to estimate plausible futures of agricultural land on a timescale of 20–50 years. The model examines the East Anglian and North West regions of the United Kingdom at a grid resolution of 5 × 5 km, and for each scenario estimates the most likely cropping and its profitability at each location, and classifies land use as arable, intensive or extensive grassland or abandoned. From a modelling viewpoint the metamodel approach enables iteration. It is thus possible to determine how product prices change so that production meets demand. The results of the study show that in East Anglia cropping remains quite stable over a wide range of scenarios, though grassland is eliminated in scenarios with the 2050s High climate scenario – almost certainly due to the low yield in the drier conditions. In the North West there is a very much greater range of outcomes, though all scenarios suggest a reduction in grassland with the greatest in the 2050s High climate scenario combined with the “Regional Stewardship” (environmental) socio-economic scenario. The effects of the predicted changes in land use on plant species showed suitability for species to vary greatly, particularly between the socio-economic scenarios, due to detrimental effects from increases in nitrogen fertilisation. A complete simulation with the Regional Impact Simulator takes around 15 seconds (computer-dependent), which users who responded felt was adequate or better than adequate. The main areas for future improvement, such as the speed of the system, user interaction and the accuracy and detail of the modelling, are c

Focusing on genomic and phenomic aberrations in non-melanotic skin cancers

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Focussing on genomic and phenomic correlations in respiration of non-melanotic skin cancers

In recent years, with the development of techniques in modern molecular biology, it has become possible to study the genetic basis of carcinogenesis down to the level of DNA sequence. Major advances have been made in our understanding of the genes involved in cell cycle control and descriptions of mutations in those genes. These developments have led to the definition of the role of specific oncogenes and tumour suppressor genes in several cancers, including, for example, colon cancers and some forms of breast cancer. Work reported from our laboratory has led to the identification of a number of candidate genes involved in the development of non-melanotic skin cancers. In this chapter, we attempt to further explain the observed (phenomic) alterations in metabolic pathways associated with oxygen consumption with the changes at the genetic level

The impact of herbicide management on long-term changes in the diversity and species composition of weed populations

Field vegetable systems face challenges to maintain sustainable weed management, including a reduction in available herbicides and encouragement towards reduced tillage. In a 9-year study, six herbicide products were compared, each at three rates, with a single product per plot. These were assessed in a minimal cultivation system designed to exert maximum pressure for change in weed populations, to assess for predictable changes in these populations. Weed density and species number declined with increasing herbicide rate, confirming that some species are able to survive in reduced rates. Pre-emergence herbicides resulted in a larger number of species, greater species diversity and lower species dominance, compared with post-emergence products. Species numbers increased over the first 6 years, with emergence periodicity coinciding with springtime soil disturbance. The number of species with ecological functional value increased in response to repeated use of single herbicide products. Observed species shifts illustrated complex responses to the combination of three separate drivers: changes in the dominant periodicity associated with tillage timing; a response to herbicide product and rate related to species susceptibility; and changes in community dynamics caused by variability in weather and the interaction with herbicide efficacy. Improved understanding of the effects on weed communities of the interactions between these drivers and the cropping system is essential in achieving a balance between sustainable weed management and the provision of ecological function

Analysis of Sdhd and Mmp12 in an affected solar keratosis and control cohort

The incidence of Squamous Cell Carcinoma (SCG) is growing in certain populations to the extent that it is now the most common skin lesion in young men and women in high ultraviolet exposure regions such as Queensland. In terms of incidence up to 40% of the Australian population over 40 years of age is thought to possess the precancerous Solar Keratosis (SK) lesion and with a small, but significant, chance of progression into SCC, understanding the genetic events that play a role in this process is essential. The major aims of this study were to analyse whole blood derived samples for DNA aberrations in genes associated with tumour development and cellular maintenance, with the ultimate aim of identifying genes associated with non-melanoma skin cancer development. More specifically the first aim of this project was to analyse the SDHD and MMP12 genes via Dual-Labelled Probe Real-Time PCR for copy number aberrations in an affected Solar Keratosis and control cohort. It was found that 12 samples had identifiable copy-number aberrations in either the SDHD or MMP12 gene (this means that a genetic section of either of these two genes is aberrantly amplified or deleted), with five of the samples exhibiting aberrations in both genes. The significance of this study is the contribution to the knowledge of the genetic pathways that are malformed in the progression and development of the pre-cancerous skin lesion Solar Keratosis. © 2008 Springer Science+Business Media, LLC

Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin

Background Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. Objectives We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. Methods Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. Results We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0Æ008). The TT ⁄tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT ⁄tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT ⁄tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA ⁄aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. Conclusions The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development