Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

INTRODUCTION: Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk. METHODS: We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA(n), 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. RESULTS: There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. CONCLUSION: We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women

The integrated analysis of metabolic and protein interaction networks reveals novel molecular organizing principles

Background: The study of biological interaction networks is a central theme of systems biology. Here, we investigate the relationships between two distinct types of interaction networks: the metabolic pathway map and the protein-protein interaction network (PIN). It has long been established that successive enzymatic steps are often catalyzed by physically interacting proteins forming permanent or transient multi-enzymes complexes. Inspecting high-throughput PIN data, it was shown recently that, indeed, enzymes involved in successive reactions are generally more likely to interact than other protein pairs. In our study, we expanded this line of research to include comparisons of the underlying respective network topologies as well as to investigate whether the spatial organization of enzyme interactions correlates with metabolic efficiency. Results: Analyzing yeast data, we detected long-range correlations between shortest paths between proteins in both network types suggesting a mutual correspondence of both network architectures. We discovered that the organizing principles of physical interactions between metabolic enzymes differ from the general PIN of all proteins. While physical interactions between proteins are generally dissortative, enzyme interactions were observed to be assortative. Thus, enzymes frequently interact with other enzymes of similar rather than different degree. Enzymes carrying high flux loads are more likely to physically interact than enzymes with lower metabolic throughput. In particular, enzymes associated with catabolic pathways as well as enzymes involved in the biosynthesis of complex molecules were found to exhibit high degrees of physical clustering. Single proteins were identified that connect major components of the cellular metabolism and may thus be essential for the structural integrity of several biosynthetic systems. Conclusion: Our results reveal topological equivalences between the protein interaction network and the metabolic pathway network. Evolved protein interactions may contribute significantly towards increasing the efficiency of metabolic processes by permitting higher metabolic fluxes. Thus, our results shed further light on the unifying principles shaping the evolution of both the functional (metabolic) as well as the physical interaction network

Healing through culturally embedded practice: an investigation of counsellors’ and clients’ experiences of Buddhist Counselling in Thailand

This thesis is concerned with an exploration of counsellors’ and clients’ lived experiences of Buddhist Counselling, an indigenous Buddhist-based counselling approach in Thailand. Over the past decade, Buddhist Counselling has received a growing interest from Thai counselling trainees and practitioners, and it has also expanded to serve Thai people in various settings. Research on Buddhist Counselling is very limited and most of the existing studies in the field have focused on measuring the effectiveness of the approach. While these studies have consistently indicated the positive effects of Buddhist Counselling on psychological improvement across several population groups, the significant questions of how Buddhist Counselling brings about such outcome and how it is experienced are still largely unanswered. Moreover, existing research is concentrated much more on clients’ views than counsellors’ views, although counsellors’ views of their counselling practice can also serve as a knowledge base of the field. This thesis thus sets out to contribute to rectifying this omission by exploring Buddhist Counselling from the perspectives of both counsellors and clients. The thesis is based on two qualitative studies. The first study addressed Buddhist Counselling from the perspective of five counsellors through a focus group and semi-structured interviews. The second study explored Buddhist Counselling from the perspective of three clients, using two semi-structured interviews with each of them. All data received were analysed using interpretative phenomenological analysis (IPA). The study reveals counsellors’ and clients’ overall positive experience of engaging in Buddhist Counselling. Central to the accounts of the counsellors are the following perceptions: that their practice of Buddhist Counselling is culturally congruent with the existing values and beliefs of both themselves and their clients; that their personal and professional congruence is key to their therapeutic efficacy; and that they enhance such congruence through their application of Buddhist ideas and practices in their daily lives. Key to the clients’ accounts is their emphasis on the significant roles of the counsellors’ Buddhist ideas and personal qualities, and of their religious practices in facilitating healing and change. Key shared findings from both studies reveal that the participants’ accounts of their cultural background and their experiences of Buddhist Counselling are intertwined. Adopting hermeneutics to address this intertwinement, I reveal the cultural and moral dimensions underlying the practice of Buddhist Counselling. Based on such revelation, I suggest that Buddhist Counselling in particular, as well as psychotherapy in general, should be better understood as a historically situated, culturally bound, and morally constituted activity of people who are concerned with improving the quality of their lives and their community, rather than the transcultural and merely relational work of morally-neutral practitioners