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Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

ABSTRACT: BACKGROUND:There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (?BMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. METHODS:A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ?BMI in participants over 40?years of age with three consecutive BMI time points (n?=?4162). Four GWAS of ?BMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418?365 single-nucleotide polymorphisms (SNPs). RESULTS:Two SNPs reached a level of genome-wide significance (P?

SUBMITTER: McDonald MN

PROVIDER: S-EPMC5476850 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

McDonald Merry-Lynn Noelle MN Won Sungho S Mattheisen Manuel M Castaldi Peter J PJ Cho Michael H MH Rutten Erica E Hardin Megan M Yip Wai-Ki WK Rennard Stephen I SI Lomas David A DA Wouters Emiel F M EFM Agusti Alvar A Casaburi Richard R Lange Christoph P CP O'Connor George G Hersh Craig P CP Silverman Edwin K EK

Journal of cachexia, sarcopenia and muscle 20170102 3

<h4>Background</h4>There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.<h4>Methods</h4>A li ...[more]

PMID: 28044437

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Project description:ImportanceThe incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity.ObjectivesTo investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight.Design, setting, and participantsThis investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307?677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016.Main outcomes and measuresChildhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (?55 years) or late (>55 years) age at diagnosis.ResultsThe study cohort comprised 307?677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations.Conclusions and relevanceIndependent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.

Project description:IntroductionIdentification of clinical characteristics associated with prognosis for idiopathic pulmonary fibrosis (IPF) may help to guide management decisions. This analysis utilized data from the Pulmonary Fibrosis Foundation Patient Registry to examine the relationships between clinical outcomes and both body mass index (BMI) at study enrollment (hereafter referred to as baseline BMI) and annualized percent change in body weight in patients with IPF in a real-world setting.MethodsThe following outcomes over 24 months were stratified by baseline BMI and annualized percent change in body weight: all-cause mortality; annualized change in percent predicted forced vital capacity (%FVC), percent predicted diffusing capacity for carbon monoxide, and 6-min walk distance; all-cause and respiratory-related hospitalizations; and acute exacerbations.ResultsOverall, 600 patients with IPF were included (baseline BMI: < 25 kg/m2, n = 120; 25 to < 30 kg/m2, n = 242; ≥ 30 kg/m2, n = 238; annualized percent change in body weight: no loss, n = 95; > 0% to < 5% loss, n = 425; ≥ 5% loss, n = 80). Enrollment demographics and characteristics were generally similar across subgroups. There was no association between mortality and BMI. All-cause mortality was lower among patients who experienced no annualized weight loss versus those with ≥ 5% (OR [95% CI] 3.28 [1.15, 10.95]) or > 0 to < 5% weight loss (OR [95% CI] 2.83 [1.14, 8.62]) over 24 months. Patients with baseline BMI < 25 kg/m2 had a significantly greater estimated annualized decline in %FVC versus patients with baseline BMI ≥ 30 kg/m2 (difference [95% CI] 1.47 [0.01, 2.93]). No relationship was observed between %FVC and weight loss. Other clinical outcomes were generally similar across subgroups.ConclusionsSome clinical outcomes may be worse in patients with IPF who have a low BMI (< 25 kg/m2) or who experience weight loss over 24 months, but the causation for these relationships is unknown. These results may help to inform management decisions for patients with IPF.ClinicaltrialsGov identifierNCT02758808.

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Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

Publications

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

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