The influence of personal BMI on body size estimations and sensitivity to body size change in anorexia spectrum disorders

In this cross-sectional study, we investigated the influence of personal BMI on body size estimation in 42 women who have symptoms of anorexia (referred to henceforth as anorexia spectrum disorders, ANSD), and 100 healthy controls. Low BMI control participants over-estimate their size and high BMI controls under-estimate, a pattern which is predicted by a perceptual phenomenon called contraction bias. In addition, control participants' sensitivity to size change declines as their BMI increases as predicted by Weber's law. The responses of women with ANSD are very different. Low BMI participants who have ANSD are extremely accurate at estimating body size and are very sensitive to changes in body size in this BMI range. However, as BMI rises in the ANSD participant group, there is a rapid increase in over-estimation concurrent with a rapid decline in sensitivity to size change. We discuss the results in the context of signal detection theory

Distorted body image influences body schema in individuals with negative bodily attitudes

There is now a considerable body of evidence to suggest that internal representations of the body can be meaningfully separated into at least two general levels; body image as a perceptual construct and body schema as a motor metric. However, recent studies with eating disordered individuals have suggested that there may in fact be more interaction between these two representations than first thought. We aimed to investigate how body image might act to influence body schema within a typical, healthy population. 100 healthy adult women were asked to judge the smallest gap between a pair of sliding doors that they could just pass through. We then determined whether these estimates were sufficient to predict the size of the smallest gap that they could actually pass through, or whether perceptual and attitudinal body image information was required in order to make these predictions. It was found that perceptual body image did indeed mediate performance on the egocentric (but not allocentric) motor imagery affordance task, but only for those individuals with raised body image concerns and low self-esteem; body schema was influenced by both the perceptual and attitudinal components of body image in those with more negative bodily attitudes. Furthermore, disparities between perceived versus actual size were associated with body parts that had larger variations in adipose/muscle-dependent circumference. We therefore suggest that it may be the affective salience of a distorted body representation that mediates the degree to which it is incorporated into the current body state

Men's perception of current and ideal body composition and the influence of media internalization on body judgements

Introduction: To determine men's body ideals and the factors that influence these choices, this study used a matrix of computer generated (CG) male bodies (based on an analysis of 3D scanned real bodies) which independently varied in fat and muscle content. Methods: Two hundred and fifty-eight male participants completed a range of psychometric measures to index body concerns and body ideal internalization and then chose the CG body that best reflected their own current body, as well as the body that reflected their personal ideal. A subset of participants was then retested to check that these judgements were stable over time. Results: While judgements of the ideal body seem to be influenced by a shared appearance ideal, the degree to which this ideal was internalized showed significant variability between participants. The effect of this internalization was reflected in the difference between the estimated current body and the ideal. Discussion: Higher internalization led to a preference for higher muscle and lower fat content. This preference was most marked for fat content, although reducing adiposity also made the underlying musculature more salient. Additionally, the ideal body composition was modulated by the composition the participant believed his current body had (i.e., it seemed that a participant's ideal body was anchored by what they believed to be their current body and what change was possible from this starting point)

Men's perception of current and ideal body composition and the influence of media internalization on body judgements

Introduction: To determine men's body ideals and the factors that influence these choices, this study used a matrix of computer generated (CG) male bodies (based on an analysis of 3D scanned real bodies) which independently varied in fat and muscle content. Methods: Two hundred and fifty-eight male participants completed a range of psychometric measures to index body concerns and body ideal internalization and then chose the CG body that best reflected their own current body, as well as the body that reflected their personal ideal. A subset of participants was then retested to check that these judgements were stable over time. Results: While judgements of the ideal body seem to be influenced by a shared appearance ideal, the degree to which this ideal was internalized showed significant variability between participants. The effect of this internalization was reflected in the difference between the estimated current body and the ideal. Discussion: Higher internalization led to a preference for higher muscle and lower fat content. This preference was most marked for fat content, although reducing adiposity also made the underlying musculature more salient. Additionally, the ideal body composition was modulated by the composition the participant believed his current body had (i.e., it seemed that a participant's ideal body was anchored by what they believed to be their current body and what change was possible from this starting point)

View-dependent accuracy in body mass judgements of female bodies

A fundamental issue in testing body image perception is how to present the test stimuli. Previous studies have almost exclusively used images of bodies viewed in front-view, but this potentially obscures key visual cues used to judge adiposity reducing the ability to make accurate judgements. A potential solution is to use a three-quarter view, which combines visual cues to body fat that can be observed in front and profile. To test this hypothesis, 20 female observers completed a 2-alternative forced choice paradigm to determine the smallest difference in body fat detectable in female bodies in front, three-quarter, and profile view. There was a significant advantage for three-quarter and profile relative to front-view. Discrimination accuracy is predicted by the saliency of stomach depth, suggesting that this is a key visual cue used to judge body mass. In future, bodies should ideally be presented in three-quarter to accurately assess body size discrimination

SNP-SNP interaction analysis of NF-kappa B signaling pathway on breast cancer survival

In breast cancer, constitutive activation of NF-kappa B has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-kappa B pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI= 3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI= 0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-kappa B pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.Peer reviewe

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the