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Metabolic health reduces risk of obesity-related cancer in framingham study adults.

ABSTRACT: BACKGROUND:It is unknown whether the risk for obesity-related cancers differs between metabolically unhealthy and healthy overweight/obese adults. METHODS:Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and random blood glucose in Framingham Heart Study adults (n = 3,763) ages 55 to 69 years were used to estimate risks of obesity-related cancers (n = 385), including postmenopausal breast, female reproductive, colon, liver, gallbladder, pancreas, and kidney cancers, as well as esophageal adenocarcinomas. Multivariable-adjusted Cox proportional hazards models were used to estimate risk for obesity-related cancers associated with body fat and metabolic health (as defined by glucose levels) among subjects in three risk groups (vs. referent group with normal weight/normal glucose): normal weight/elevated glucose, overweight/normal glucose, and overweight/elevated glucose. RESULTS:Overweight adults [BMI ? 25 or WHtR ? 0.51 (men) and ?0.57 (women)] with elevated glucose (?125 mg/dL) had a statistically significant 2-fold increased risk of developing obesity-related cancer, whereas overweight adults with normal glucose had a 50% increased risk. Normal-weight adults with elevated glucose had no excess cancer risk. The effects of BMI and WHtR were independent of one another. Finally, overweight women with elevated blood glucose had a 2.6-fold increased risk [95% confidence interval (CI), 1.4-4.9] of female reproductive (cervical, endometrial, uterine cancers) and postmenopausal breast cancers, whereas overweight women with normal glucose levels had only a 70% increased risk (95% CI, 1.1-2.5). CONCLUSION:These results suggest that cancer risk may be lower among metabolically healthy overweight/obese older adults than among overweight/obese adults with metabolic dysfunction. IMPACT:Metabolic dysfunction and obesity act synergistically to increase cancer risk.

SUBMITTER: Moore LL

PROVIDER: S-EPMC4184957 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Metabolic health reduces risk of obesity-related cancer in framingham study adults.

Moore Lynn L LL Chadid Susan S Singer Martha R MR Kreger Bernard E BE Denis Gerald V GV

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140710 10

<h4>Background</h4>It is unknown whether the risk for obesity-related cancers differs between metabolically unhealthy and healthy overweight/obese adults.<h4>Methods</h4>Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and random blood glucose in Framingham Heart Study adults (n = 3,763) ages 55 to 69 years were used to estimate risks of obesity-related cancers (n = 385), including postmenopausal breast, female reproductive, colon, liver, gallbladder, pancre ...[more]

PMID: 25012997

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Project description:PurposeThe insulin-signaling pathway plays a pivotal role in cancer biology; however, evidence of genetic alterations in human studies is limited. This case-control study nested within the Framingham Heart Study (FHS) examined the association between inherited genetic variation in the insulin receptor (INSR) gene and obesity-related cancer risk.MethodsThe study sample consisted of 1,475 controls and 396 cases from the second familial generation of the FHS. Participants who provided consent were genotyped. Nineteen single-nucleotide polymorphisms (SNPs) in the INSR gene were investigated in relation to risk of obesity-related cancers combined and breast, prostate and colorectal cancers. Generalized estimation equation models controlling for familial correlations and include age, sex, smoking and body mass index as covariates, assuming additive models, were used.ResultsThree SNPs, rs2059807, s8109559 and rs919275, were significantly associated with obesity-related cancers (p value < 0.02) with the most significantly associated SNP being rs2059807 (p value = 0.008). Carriers of two copies of SNP rs2059807 risk allele T were significantly less prevalent among subjects with obesity-related cancers [f(TT)cases = 14 vs. f(TT)controls = 18 %; OR 1.23]. In exploratory analyses evaluating site-specific cancers, the INSR rs2059807 association with these cancers was consistent with that observed for the main outcome (ORs colorectal cancer = 1.5, breast cancer = 1.29, prostate = 1.06). There was no statistically significant interaction between the INSR-SNP and blood glucose in relation to obesity-related cancer.ConclusionsThe INSR gene is implicated in obesity-related cancer risk, as 3 of 19 SNPs were nominally associated, after false discovery rate (FDR) correction, with the main outcome. Risk allele homozygotes (rs2059807) were less prevalent among subjects with obesity-related cancer. These results should be replicated in other populations to confirm the findings.

Project description:Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (?88 cm); elevated blood pressure (?130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m2 with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m2 and ?1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR?=?1.26, 95% CI: 1.01-1.56), as did women with a BMI ?25 kg/m2 and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR?=?1.24, 95% CI: 0.99-1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ?88 cm, waist circumference ?80 cm, and waist-hip ratio ?0.85 of 1.58, 95% CI: 1.02-2.46; 1.38, 95% CI: 1.09-1.75; and 1.38, 95% CI: 1.02-1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR?=?0.71, 95% CI: 0.52-0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.

Project description:BackgroundSex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex.MethodsA total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models.ResultsWe found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape.ConclusionsThere was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

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Metabolic health reduces risk of obesity-related cancer in framingham study adults.

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Metabolic health reduces risk of obesity-related cancer in framingham study adults.

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