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Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study.

ABSTRACT: BACKGROUND:Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies. METHODS:We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 case-control pairs) and colorectal (831 case-control pairs) cancer in an independent sample in MEC. Abdominal MRI-derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed. RESULTS:The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm2 was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86-1.39), 1.48 (1.16-1.89); P trend = 0.002] but not with colorectal cancer (P = 0.84), although an association [1.00, 0.98 (0.68-1.39), 1.24 (0.88-1.76); P trend = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (P heterogeneity = 0.06). CONCLUSIONS:The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations. IMPACT:These findings provide specific evidence for a role of VAT in breast cancer.

SUBMITTER: Le Marchand L

PROVIDER: S-EPMC7196505 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study.

Le Marchand Loïc L Wilkens Lynne R LR Castelfranco Ann M AM Monroe Kristine R KR Kristal Bruce S BS Cheng Iona I Maskarinec Gertraud G Hullar Meredith A MA Lampe Johanna W JW Shepherd John A JA Franke Adrian A Ernst Thomas T Lim Unhee U

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20200304 5

<h4>Background</h4>Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies.<h4>Methods</h4>We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 ca ...[more]

PMID: 32132150

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Project description:Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements.

Project description:BackgroundVisceral adiposity is an important risk factor for cardiometabolic diseases.ObjectiveTo determine whether the Metabolic Score for Visceral Fat (METS-VF) is more effective than other adiposity indices in predicting visceral fat area (VFA).MethodsIn this single-center and cross-sectional study, we included patients aged 20-50 years, without diabetes and coronary artery disease, who underwent computed tomography (CT) including the third lumbar vertebra. Age, blood pressure, waist circumference (WC), hip circumference, fasting lipids, and glucose were assessed. VFA was measured by cross-sectional examination of CT. The correlation of WC, body mass index (BMI), waist-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), and METS-VF with VFA was analyzed by correlation analysis. The cut-off values and area under the curve (AUC) for identifying increased VFA (>130 cm2) were determined.ResultsWe included 185 individuals with mean age 38.2 ± 8 and female predominance (58.4%). There was a significant positive correlation between all indices and VFA (p<0.001). ROC analysis revealed that METS-VF and WC demonstrated the highest predictive value for identifying increased VFA. In both men (p=0.001) and women (p<0.001), METS-VF (AUC 0.922 and 0.939, respectively) showed a significant superiority over ABSI (AUC 0.702 and 0.658, respectively), and VAI (AUC 0.731 and 0.725, respectively). Additionally, in women, its superiority over WHR (AUC 0.807) was also statistically significant (p=0.003). We identified a METS-VF cut-off point >6.4 in males >6.5 in females and WC cut-off point >88 cm in males (AUC 0.922), >90.5 cm in females (AUC 0.938).ConclusionMETS-VF is strongly associated with visceral adiposity and better to predict increased VFA. However, its superiority over WC, BMI, BRI, and LAP was not significant. The results emphasize that WC is more appealing as screening indicator for visceral adiposity considering its easy use.Clinical trial registry nameClinicaltrials.gov (http://www.clinicaltrials.gov).Clinical trial registry urlhttps://clinicaltrials.gov/ct2/show/NCT05648409.Clinical trial registry numberNCT05648409.

Project description:The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

Project description:BackgroundVisceral adiposity, more so than overall adiposity, is associated with chronic disease and mortality. There has been, to our knowledge, little research exploring the association between diet quality and visceral adipose tissue (VAT) among a mulitethnic population aged 18-80 y.ObjectiveThe primary objective of this cross-sectional analysis was to examine the association between diet quality [Healthy Eating Index-2010 (HEI-2010) scores] and VAT among a multiethnic population of young, middle, and older aged adults in the United States. Secondary objectives were to repeat these analyses with overall adiposity and blood-based biomarkers for type 2 diabetes and cardiovascular disease risk as outcome measures.MethodsA total of 540 adults (dropped out: n = 4; age: 18-40 y, n = 220; 40-60 y, n = 183; 60-80 y, n = 133) were recruited across 3 sites (Honolulu County, San Francisco, and Baton Rouge) for the Shape Up! Adults study. Whole-body DXA, anthropometry, fasting blood draw, and questionnaires (food frequency, physical activity, and demographic characteristics) were completed. Linear regression was used to assess the associations between HEI-2010 tertiles and VAT and secondary outcome measures among all participants and age-specific strata, while adjusting for known confounders.ResultsVAT, BMI (kg/m2), body fat percentage, total body fat, trunk fat, insulin, and insulin resistance were inversely related to diet quality (all P values < 0.004). When stratified by age, diet quality was inversely associated with VAT among participants aged 60-80 y (P < 0.006) and VAT/subcutaneous adipose tissue (SAT) among participants aged 40-60 y (P < 0.008).ConclusionsHigher-quality diet was associated with lower VAT, overall adiposity, and insulin resistance among this multiethnic population of young, middle, and older aged adults with ages ranging from 18 to 80 y. More specifically, adherence to a high-quality diet may minimize VAT accumulation in adults aged 60-80 y and preferentially promote storage of SAT compared with VAT in adults aged 40-60 y.This study was registered at clinicaltrials.gov as NCT03637855.

Dataset Information

Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study.

Publications

Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study.

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