Showing papers by "University of Southern California published in 2007"

American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography

Abstract: New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20-25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.

Genome-wide association study identifies novel breast cancer susceptibility loci

Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

Abstract: The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed "fragment recruitment," addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed "extreme assembly," made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS.

Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes

Abstract: Extensive studies are currently being performed to associate disease susceptibility with one form of genetic variation, namely, single-nucleotide polymorphisms (SNPs). In recent years, another type of common genetic variation has been characterized, namely, structural variation, including copy number variants (CNVs). To determine the overall contribution of CNVs to complex phenotypes, we have performed association analyses of expression levels of 14,925 transcripts with SNPs and CNVs in individuals who are part of the International HapMap project. SNPs and CNVs captured 83.6% and 17.7% of the total detected genetic variation in gene expression, respectively, but the signals from the two types of variation had little overlap. Interrogation of the genome for both types of variants may be an effective way to elucidate the causes of complex phenotypes and disease in humans.

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocri...

Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus.

Abstract: The Fifth International Workshop-Conference on Gestational Diabetes Mellitus (GDM) was held in Chicago, IL, 11–13 November 2005 under the sponsorship of the American Diabetes Association. The meeting provided a forum for review of new information concerning GDM in the areas of pathophysiology, epidemiology, perinatal outcome, long-range implications for mother and her offspring, and management strategies. New information and recommendations related to each of these major topics are summarized in the report that follows. The issues regarding strategies and criteria for the detection and diagnosis of GDM were not reviewed or discussed in detail, since it is anticipated that the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study will provide data in mid-2007 that will foster the development of criteria for the diagnosis of GDM that are based on perinatal outcomes. Thus, for the interim, the participants of the Fifth International Workshop-Conference on GDM endorsed a motion to continue use of the definition, classification criteria, and strategies for detection and diagnosis of GDM that were recommended at the Fourth Workshop-Conference. Those guidelines are reproduced (with minor modifications) in this article in appendix Tables 1 and 2. The invited lectures, topical discussions, and posters presented at the conference and the invited manuscripts that appear in this issue of Diabetes Care served as the basis for the following summary and recommendations. ### Pathophysiology #### General considerations. Current diagnostic criteria assign the diagnosis of GDM to women with glucose levels in the upper ∼5–10% of the population distribution. The hyperglycemia varies in severity from glucose concentrations that would be diagnostic of diabetes outside of pregnancy to concentrations that are asymptomatic and only slightly above normal, but associated with some increased risk of fetal morbidity. Like all forms of hyperglycemia, GDM is characterized by insulin levels that are insufficient to meet insulin demands. The causes of pancreatic β-cell dysfunction that …

A set-theoretic approach to organizational configurations

Abstract: I argue that research on organizational configurations has been limited by a mismatch between theory and methods and introduce set-theoretic methods as a viable alternative for overcoming this mismatch. I demonstrate the value of such methods for studying organizational configurations and discuss their applicability for examining equifinality and limited diversity among configurations, as well as their relevance to other research fields such as complementarities theory, complexity theory, and the resource-based view

When Morality Opposes Justice: Conservatives Have Moral Intuitions that Liberals May Not Recognize

Abstract: Researchers in moral psychology and social justice have agreed that morality is about matters of harm, rights, and justice. With this definition of morality, conservative opposition to social justice programs has appeared to be immoral, and has been explained as a product of various non-moral processes, such as system justification or social dominance orientation. In this article we argue that, from an anthropological perspective, the moral domain is usually much broader, encompassing many more aspects of social life and valuing institutions as much or more than individuals. We present theoretical and empirical reasons for believing that there are in fact five psychological systems that provide the foundations for the world's many moralities. The five foundations are psychological preparations for detecting and reacting emotionally to issues related to harm/care, fairness/reciprocity, ingroup/loyalty, authority/respect, and purity/sanctity. Political liberals have moral intuitions primarily based upon the first two foundations, and therefore misunderstand the moral motivations of political conservatives, who generally rely upon all five foundations.

Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes: One-Year Results of the Look AHEAD Trial

Abstract: Objective: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes one-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. Research Design and Methods: A multi-centered randomized controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with body mass index >25 kg/m2 (>27 kg/m2 if taking insulin). An Intensive Lifestyle Intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared to a Diabetes Support and Education (DSE) condition. Results: Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (p Conclusions: At 1 year, ILI resulted in clinically significant weight loss in persons with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk. Trial Registration: clinicaltrials.gov Identifier: NCT00017953

Relaxation in a completely integrable many-body quantum system: an ab initio study of the dynamics of the highly excited states of 1D lattice hard-core bosons.

Abstract: In this Letter we pose the question of whether a many-body quantum system with a full set of conserved quantities can relax to an equilibrium state, and, if it can, what the properties of such a state are. We confirm the relaxation hypothesis through an ab initio numerical investigation of the dynamics of hard-core bosons on a one-dimensional lattice. Further, a natural extension of the Gibbs ensemble to integrable systems results in a theory that is able to predict the mean values of physical observables after relaxation. Finally, we show that our generalized equilibrium carries more memory of the initial conditions than the usual thermodynamic one. This effect may have many experimental consequences, some of which have already been observed in the recent experiment on the nonequilibrium dynamics of one-dimensional hard-core bosons in a harmonic potential [T. Kinoshita et al., Nature (London) 440, 900 (2006)].

Communication, Power and Counter-power in the Network Society

Abstract: This article presents a set of grounded hypotheses on the relationship between communication and power relationships in the technological context that characterizes the network society. Based on a selected body of communication literature, and of a number of case studies and examples, it argues that the media have become the social space where power is decided. It shows the direct link between politics, media politics, the politics of scandal, and the crisis of political legitimacy in a global perspective. It also puts forward the notion that the development of interactive, horizontal networks of communication has induced the rise of a new form of communication, mass self-communication, over the Internet and wireless communication networks. Under these conditions, insurgent politics and social movements are able to intervene more decisively in the new communication space. However, corporate media and mainstream politics have also invested in this new communication space. As a result of these processes, mass media and horizontal communication networks are converging. The net outcome of this evolution is a historical shift of the public sphere from the institutional realm to the new communication space.

Damage to the prefrontal cortex increases utilitarian moral judgements

Abstract: The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions, produce an abnormally 'utilitarian' pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person's life to save a number of other lives). In contrast, the VMPC patients' judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements.

Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche

Abstract: The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.

Damage to the insula disrupts addiction to cigarette smoking.

Abstract: A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking.

Epigenetic stem cell signature in cancer.

Abstract: Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.

Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial.

Abstract: Purpose: Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. Methods: Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan-Meier) Results: As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5-10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P = 0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P = 0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P = 0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). Conclusion: Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial.

Information Technology and the Changing Fabric of Organization

Abstract: Technology has been an important theme in the study of organizational form and function since the 1950s. However, organization science's interest in this relationship has declined significantly over the past 30 years, a period during which information technologies have become pervasive in organizations and brought about significant changes in them. Organizing no longer needs to take place around hierarchy and the collection, storage, and distribution of information as was the case with “command and control” bureaucracies in the past. The adoption of innovations in information technology (IT) and organizational practices since the 1990s now make it possible to organize around what can be done with information. These changes are not the result of information technologies per se, but of the combination of their features with organizational arrangements and practices that support their use. Yet concepts and theories of organizational form and function remain remarkably silent about these changes. Our analysis offers five affordances---visualizing entire work processes, real-time/flexible product and service innovation, virtual collaboration, mass collaboration, and simulation/synthetic reality---that can result from the intersection of technology and organizational features. We explore how these affordances can result in new forms of organizing. Examples from the articles in this special issue “Information Technology and Organizational Form and Function” are used to show the kinds of opportunities that are created in our understanding of organizations when the “black boxes” of technology and organization are simultaneously unpacked.

Validity Issues in Narrative Research.

Abstract: Attention to the judgments about the validity of research-generated knowledge claims is integral to all social science research. During the past several decades, knowledge development has been split into two communities: conventional researchers and reformist researchers. Narrative research is positioned within the reformist community. The two communities use different kinds of data and employ different analytic processes. In both communities, researchers develop arguments to convince readers of the validity of their knowledge claims. Both need to respond to threats to validity inherent in their designs. The threats particular to narrative research relate to two areas: the differences in people's experienced meaning and the stories they tell about this meaning and the connections between storied texts and the interpretations of those texts.

We feel, therefore we learn: The relevance of affective and social neuroscience to education.

Abstract: Recent advances in neuroscience are highlighting connections between emotion, social functioning, and decision making that have the potential to revolutionize our understanding of the role of affect in education. In particular, the neurobiological evidence suggests that the aspects of cognition that we recruit most heavily in schools, namely learning, attention, memory, decision making, and social functioning, are both profoundly affected by and subsumed within the processes of emotion; we call these aspects emotional thought. Moreover, the evidence from brain-damaged patients suggests the hypothesis that emotion-related processes are required for skills and knowledge to be transferred from the structured school environment to real-world decision making because they provide an emotional rudder to guide judgment and action. Taken together, the evidence we present sketches an account of the neurobiological underpinnings of morality, creativity, and culture, all topics of critical importance to education. Our hope is that a better understanding of the neurobiological relationships between these constructs will provide a new basis for innovation in the design of learning environments. Note: The lead author appears twice in this issue of LEARNing Landscapes: first in the reprint cited below, and next, in an accompanying follow-up article that features poetry from her daughter Nora Ming-Min Yang. Immordino-Yang, M.H., & Damasio, A.R. (2007). We feel, therefore we learn: The relevance of affective and social neuroscience to education. Mind, Brain and Education, 1(1), 3–10. * Reprinted in Jossey-Bass Reader on the Brain and Learning (pp. 183–198). San Francisco: Jossey-Bass.

Modular Self-Reconfigurable Robot Systems [Grand Challenges of Robotics]

Abstract: The field of modular self-reconfigurable robotic systems addresses the design, fabrication, motion planning, and control of autonomous kinematic machines with variable morphology. Modular self-reconfigurable systems have the promise of making significant technological advances to the field of robotics in general. Their promise of high versatility, high value, and high robustness may lead to a radical change in automation. Currently, a number of researchers have been addressing many of the challenges. While some progress has been made, it is clear that many challenges still exist. By illustrating several of the outstanding issues as grand challenges that have been collaboratively written by a large number of researchers in this field, this article has shown several of the key directions for the future of this growing field

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

Abstract: ContextLaboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.ObjectiveTo assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.Design, Setting, and ParticipantsA double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.InterventionParticipants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).Main Outcome MeasuresThe primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ≥3 adenomas).Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. ConclusionsFolic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.Trial Registration clinicaltrials.gov Identifier: NCT00272324

Detection and Tracking of Multiple, Partially Occluded Humans by Bayesian Combination of Edgelet based Part Detectors

Abstract: Detection and tracking of humans in video streams is important for many applications. We present an approach to automatically detect and track multiple, possibly partially occluded humans in a walking or standing pose from a single camera, which may be stationary or moving. A human body is represented as an assembly of body parts. Part detectors are learned by boosting a number of weak classifiers which are based on edgelet features. Responses of part detectors are combined to form a joint likelihood model that includes an analysis of possible occlusions. The combined detection responses and the part detection responses provide the observations used for tracking. Trajectory initialization and termination are both automatic and rely on the confidences computed from the detection responses. An object is tracked by data association and meanshift methods. Our system can track humans with both inter-object and scene occlusions with static or non-static backgrounds. Evaluation results on a number of images and videos and comparisons with some previous methods are given.

Type-2 fuzzy sets and systems: an overview

Abstract: This paper provides an introduction to and an overview of type-2 fuzzy sets (T2 FS) and systems. It does this by answering the following questions: What is a T2 FS and how is it different from a T1 FS? Is there new terminology for a T2 FS? Are there important representations of a T2 FS and, if so, why are they important? How and why are T2 FSs used in a rule-based system? What are the detailed computations for an interval T2 fuzzy logic system (IT2 FLS) and are they easy to understand? Is it possible to have an IT2 FLS without type reduction? How do we wrap this up and where can we go to learn more?

Publicly Private and Privately Public: Social Networking on YouTube

Abstract: YouTube is a public video-sharing website where people can experience varying degrees of engagement with videos, ranging from casual viewing to sharing videos in order to maintain social relationships. Based on a one-year ethnographic project, this article analyzes how YouTube participants developed and maintained social networks by manipulating physical and interpretive access to their videos. The analysis reveals how circulating and sharing videos reflects different social relationships among youth. It also identifies varying degrees of "publicness" in video sharing. Some participants exhibited "publicly private" behavior, in which video makers' identities were revealed, but content was relatively private because it was not widely accessed. In contrast, "privately public" behavior involved sharing widely accessible content with many viewers, while limiting access to detailed information about video producers' identities.

GRP78 Induction in Cancer: Therapeutic and Prognostic Implications

Abstract: Cancer cells adapt to chronic stress in the tumor microenvironment by inducing the expression of GRP78/BiP, a major endoplasmic reticulum chaperone with Ca(2+)-binding and antiapoptotic properties. GRP78 promotes tumor proliferation, survival, metastasis, and resistance to a wide variety of therapies. Thus, GRP78 expression may serve as a biomarker for tumor behavior and treatment response. Combination therapy suppressing GRP78 expression may represent a novel approach toward eradication of residual tumors. Furthermore, the recent discovery of GRP78 on the cell surface of cancer cells but not in normal tissues suggests that targeted therapy against cancer via surface GRP78 may be feasible.

Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.

Abstract: Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.