Body Mass Index Influences the Prognostic Impact of Combined Nuclear Insulin Receptor and Estrogen Receptor Expression in Primary Breast Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Bjorner S
PROVIDER: S-EPMC5712344 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Body Mass Index Influences the Prognostic Impact of Combined Nuclear Insulin Receptor and Estrogen Receptor Expression in Primary Breast Cancer.
Björner Sofie S Rosendahl Ann H AH Simonsson Maria M Markkula Andrea A Jirström Karin K Borgquist Signe S Rose Carsten C Ingvar Christian C Jernström Helena H
Frontiers in endocrinology 20171128
The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor α (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry ...[more]
Similar Datasets
Project description:BackgroundObesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status.MethodsWe conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram.ResultsPercent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50-3.16) vs 1.33 (95% CI 1.11-1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage.ConclusionsThe combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.
| S-EPMC6448282 | biostudies-literature
Project description:Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors.Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from phase I of the Carolina Breast Cancer Study, a population-based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor (ER) status was also conducted.In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ? 30). Obesity was significantly associated with differential methylation (FDR q < 0.05) in just two gene loci in breast tumor tissue overall and in 21 loci among ER-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair.Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influence levels of gene expression within breast cells.If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research. Cancer Epidemiol Biomarkers Prev; 24(3); 580-6. ©2015 AACR.
| S-EPMC4355173 | biostudies-literature
Project description:To assess the joint relationships among body mass index, menopausal status, and breast cancer according to breast cancer subtype and estrogen-progestin medication use, we conducted a meta-analysis of 89 epidemiologic reports published in English during 1980-2012 identified through a systematic search of bibliographic databases. Pooled analysis yielded a summary risk ratio of 0.78 (95% confidence interval (CI): 0.67, 0.92) for hormone receptor-positive premenopausal breast cancer associated with obesity (body mass index (weight (kg)/height (m)(2)) ≥30 compared with <25). Obesity was associated with a summary risk ratio of 1.39 (95% CI: 1.14, 1.70) for receptor-positive postmenopausal breast cancer. For receptor-negative breast cancer, the summary risk ratios of 1.06 (95% CI: 0.70, 1.60) and 0.98 (95% CI: 0.78, 1.22) associated with obesity were null for both premenopausal and postmenopausal women, respectively. Elevated postmenopausal breast cancer risk ratios associated with obesity were limited to women who never took estrogen-progestin therapy, with risk ratios of 1.42 (95% CI: 1.30, 1.55) among never users and 1.18 (95% CI: 0.98, 1.42) among users; too few studies were available to examine this relationship according to receptor subtype. Future research is needed to confirm whether obesity is unrelated to receptor-negative breast cancer in populations of postmenopausal women with low prevalence of hormone medication use.
| S-EPMC3873844 | biostudies-literature
Project description:BackgroundObesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.MethodsPatients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided.ResultsThis study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24).ConclusionIn this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.
| S-EPMC10697786 | biostudies-literature
Project description:It is unclear whether earlier age at menarche is associated with higher body mass index (BMI) because they share a common genetic underpinning. We investigated the impact of single nucleotide polymorphisms (SNPs) influencing menarche timing on peripubertal BMI. For 556 Fels Longitudinal Study children (277 boys/279 girls) born 1928-1992, a genetic risk score (GRS(42)) was computed as the sum of the number of risk alleles in 42 putative menarche SNPs. Serial BMI Z-scores within ±6.99 years from each individual's age at peak height velocity (Age@PHV) were grouped into seven time points (-6 years, -4 years, -2 years, Age@PHV, +2 years, +4 years, and +6 years). Heritability of BMI ranged from 0.53 to 0.85 across the time points. The effect of GRS(42) on BMI Z-scores at each time point was modeled using variance components-based procedures. GRS(42) had a significant (P < 0.05) effect at every time point; an increase of one risk allele was associated with an increase of 0.03-0.08 BMI Z-scores. A separate score (GRS(29)) was computed that excluded 13 of the menarche SNPs previously documented to also influence adiposity; significant main effects were observed at Age@PHV+4 and +6 years. This finding supports a causal effect of advanced sexual development on post-Age@PHV BMI. Significant positive GRS(42) (or GRS(29))-by-birth year interactions indicate that some genetic influences on BMI have amplified over the 20th century. This gene-by-environment interaction also suggests that children with a genetic predisposition to earlier sexual development might avoid elevated BMI through alteration of their nutritional environment.
| S-EPMC3539227 | biostudies-literature
Project description:Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10(-14)), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10(-9)). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10(-20)). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36-1.45 kg/m(2) per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a 'thrifty' variant hypothesis as a factor in human obesity.
| S-EPMC5069069 | biostudies-literature
Project description:PURPOSE:Both schools and neighborhoods play important roles in determining adolescent weight status, but little is known about their relative importance, particularly in predicting long-term weight outcomes. We assessed the impacts of both school and neighborhood socioeconomic composition, social connectedness, and built environment during adolescence on weight status in young adulthood. METHODS:The study sample consisted of 14,625 respondents from Waves I and IV of the National Longitudinal Study of Adolescent to Adult Health. Data were analyzed using cross-classified multilevel modeling to examine the joint effect of adolescents' school and neighborhood predictors on body mass index (BMI) 13 years later. RESULTS:Living in a neighborhood with lower average parent education during adolescence, and attending a school with lower average parent education, were each associated with higher BMI in young adulthood. Living in a neighborhood with more physical activity resources predicted lower young adult BMI, independent of adolescent weight, parent obesity status, and demographic characteristics. School physical activity resources and perceptions of social connectedness (in the school or neighborhood) were not significantly associated with young adult BMI. CONCLUSIONS:These findings highlight the importance of school and neighborhood socioeconomic composition during adolescence on young adult weight status. Results also suggest that improving neighborhood infrastructure may promote healthy weight.
| S-EPMC6397088 | biostudies-literature
Project description:Pediatric acute lymphoblastic leukemia (ALL) therapies have been associated with many late effects, including obesity, hyperglycemia, and insulin resistance. Few data are available linking these abnormalities to specific risk factors present during ALL treatment.Retrospective cohort study with prospective follow-up. Subjects had been diagnosed with ALL at ages 1-18 years and had been off chemotherapy for >9 months. Oral glucose tolerance testing (OGTT) was performed and these results compared to demographic, treatment, and anthropomorphic data from medical records.Twenty-seven subjects (11 female) were evaluated. Mean (+/-SD) diagnosis age 5.7 +/- 3.5 years, mean study age 11.3 +/- 3.7 years, mean time off therapy 2.8 +/- 1.5 years. Six subjects had transient hyperglycemia during ALL treatment. At study time, one subject had prediabetes; eight (29.6%) had insulin resistance. Insulin resistance was not predicted by glucose levels during treatment, cumulative steroid or asparaginase dose, or type of steroid received. Body mass index (BMI) for age correlated significantly with several measures of insulin resistance, including fasting insulin, HOMA index, Matsuda index and insulin AUC (P = 0.001-0.009). Waist/hip ratio and BMI at ALL diagnosis also correlated with insulin resistance, but these factors' effects could not be separated from BMI at study time.Variations in ALL therapy and presence of transient hyperglycemia do not appear to increase risk of glucose intolerance or insulin resistance in the first few years after completion of therapy. Elevated BMI strongly predicted insulin resistance in this study, as it does in the general population.
| S-EPMC3804011 | biostudies-literature
Project description:The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m2) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95) and BCSS (HR = 2.24, 95% CI = 1.12-4.47). There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.
| S-EPMC5331962 | biostudies-literature
Project description:ImportanceBody mass index (BMI) is used to diagnose obesity in adolescents worldwide, despite evidence that weight does not scale with height squared in adolescents. To account for this, health care providers diagnose obesity using BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is accurate in adolescents.ObjectiveTo compare the accuracy of BMI vs other body fat indices of the form body mass divided by heightn in estimating body fat levels in adolescents.Design, setting, and participantsCross-sectional data from the 1999 to 2006 US National Health and Nutrition Examination Survey were analyzed between September 2015 and December 2016.Main outcomes and measuresDual-energy x-ray absorptiometry and anthropometric data were used to determine changes in body fat levels, body proportions, and the scaling relationships among body mass, height, and percent body fat. To assess the merits of each adiposity index, 3 criteria were used: stability with age, accuracy in estimating percent body fat, and accuracy in classifying adolescents as overweight vs normal weight.ResultsParticipants included 2285 non-Hispanic white participants aged 8 to 29 years. Percent body fat varied with both age and height during adolescence, invalidating the standard weight-to-height regression as the way of finding the optimal body fat index. Because the correct regression model (percent body fat is proportional to mass divided by heightn) suggested that percent body fat scales to height with an exponent closer to 3, we therefore focused on the tri-ponderal mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores. For ages 8 to 17 years, TMI yielded greater stability with age and estimated percent body fat better than BMI (R2?=?0.64 vs 0.38 in boys and R2?=?0.72 vs 0.66 in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI, 17.8%-20.0%; P?<?.001) and performed equally as well as updated BMI percentiles derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95% CI, 6.9%-9.1%; P?=?.62).Conclusions and relevanceThe tri-ponderal mass index estimates body fat levels more accurately than BMI in non-Hispanic white adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight more accurately than BMI z scores and equally as well as updated BMI percentiles but is much simpler to use than either because it does not involve complicated percentiles. Taken together, it is worth considering replacing BMI z scores with TMI to estimate body fat levels in adolescents.
| S-EPMC5710345 | biostudies-literature