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Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.

ABSTRACT: Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical activity with colorectal cancer risk in a case-control study.The analysis includes 3,041 (1,402 cases and 1,639 controls) participants in the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study in Northern Israel. Analysis was carried out separately in two sets. The first set included 1,248 subjects (625 cases, 623 controls), and the second validation set consisted of 1,793 subjects (777 cases, 1,016 controls).No association was found between the studied polymorphism and CRC risk. However, evaluation of gene environment interactions revealed an interaction between leisure time physical activity and the GH1 polymorphism, which was consistent in both sets (P(interaction) = 0.005). The genotype AA was associated with decreased risk of CRC among individuals who did not engage in any such activity (odds ratio, 0.76; 95% confidence interval, 0.52-0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity (odds ratio, 1.38; 95% confidence interval, 0.98-1.94).We found that the A allele of the rs2665802 polymorphism is associated with reduced risk of CRC only among physically inactive individuals, indicating an interaction between physical activity and the growth hormone/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted.

SUBMITTER: Khoury-Shakour S

PROVIDER: S-EPMC2665206 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.

Khoury-Shakour Sana S Gruber Stephen B SB Lejbkowicz Flavio F Rennert Hedy S HS Raskin Leon L Pinchev Mila M Rennert Gad G

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20081201 12

<h4>Unlabelled</h4>Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical ac ...[more]

PMID: 19064544

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Project description:Physical activity (PA) is associated with decreased signaling in the mTOR pathway in animal models of mammary cancer, which may indicate favorable outcomes. We examined the association between PA and protein expression in the mTOR signaling pathway in breast tumor tissue. Data on 739 patients with breast cancer, among which 125 patients had adjacent-normal tissue, with tumor expression for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-P70S6K were analyzed. Self-reported recreational PA levels during the year prior to diagnosis were classified using the Centers for Disease Control and Prevention guideline as sufficient (for moderate or vigorous) PA or insufficient PA (any PA but not meeting the guideline) or no PA. We performed linear models for mTOR protein and two-part gamma hurdle models for phosphorylated proteins. Overall, 34.8% of women reported sufficient PA; 14.2%, insufficient PA; 51.0%, no PA. Sufficient (vs. no) PA was associated with higher expression for p-P70S6K [35.8% increase; 95% confidence interval (CI), 2.6-80.2] and total phosphoprotein (28.5% increase; 95% CI, 5.8-56.3) among tumors with positive expression. In analyses stratified by PA intensity, sufficient versus no vigorous PA was also associated with higher expression levels of mTOR (beta = 17.7; 95% CI, 1.1-34.3) and total phosphoprotein (28.6% higher; 95% CI, 1.4-65.0 among women with positive expression) in tumors. The study found that guideline-concordant PA levels were associated with increased mTOR signaling pathway activity in breast tumors. Studying PA in relation to mTOR signaling in humans may need to consider the complexity of the behavioral and biological factors.SignificancePA increases energy expenditure and limits energy utilization in the cell, which can influence the mTOR pathway that is central to sensing energy influx and regulating cell growth. We studied exercise-mediated mTOR pathway activities in breast tumor and adjacent-normal tissue. Despite the discrepancies between animal and human data and the limitations of our approach, the findings provide a foundation to study the mechanisms of PA and their clinical implications.

Project description:BackgroundMaintenance of lean muscle mass and related strength is associated with lower risk for numerous chronic diseases of aging in women.ObjectiveOur aim was to evaluate whether the association between dietary protein and lean mass differs by physical activity level, amino acid composition, and body mass index categories.DesignWe performed a cross-sectional analysis of a prospective cohort.Participants/settingParticipants were postmenopausal women from the Women's Health Initiative with body composition measurements by dual-energy x-ray absorptiometry (n=8,298).Main outcome measuresOur study measured percent lean mass, percent fat mass, and lean body mass index.Statistical analyses performedLinear regression models adjusted for scanner serial number, age, calibrated energy intake, race/ethnicity, neighborhood socioeconomic status, and recreational physical activity were used to determine the relationship between protein intake and body composition measures. Likelihood ratio tests and stratified analysis were used to investigate physical activity and body mass index as potential effect modifiers.ResultsBiomarker-calibrated protein intake was positively associated with percent lean mass; women in the highest protein quintile had 6.3 percentage points higher lean mass than the lowest quintile (P<0.001). This difference rose to 8.5 percentage points for physically active women in the highest protein quintile (Pinteraction=0.023). Percent fat mass and lean body mass index were both inversely related to protein intake (both P<0.001). Physical activity further reduced percent fat mass (Pinteraction=0.022) and lean body mass index (Pinteraction=0.011). Leucine intake was associated with lean mass, as were branched chain amino acids combined (both P<0.001), but not independent of total protein. All associations were observed for normal-weight, overweight, and obese women.ConclusionsProtein consumption up to 2.02 g/kg body weight daily is positively associated with lean mass in postmenopausal women. Importantly, those that also engage in physical activity have the highest lean mass across body mass index categories.

Project description:BackgroundShort sleep is more common in the modern society. Recreational physical activity (RPA) like exercise brings both mental and physiological benefits to depression; paradoxically, lack of sleep is harmful. Evidence on the association between RPA and depression in the short sleep population is limited.MethodsParticipants with short sleep condition from the National health and Nutrition Examination Surveys (NHANES 2007-2018) were included in the present study. Short sleep condition was defined as ≤ 7 h per night. Sleep duration and RPA status were self-reported in NHANES by the Physical Activity Questionnaire using a 7-day recall method. Multivariable logistic regression was applied to evaluate the association between RPA and depression. Additionally, the non-linear relationship between RPA and depression was evaluated using the threshold effect analysis and restricted cubic spline.ResultsThis cross-sectional study comprised 6,846 adults' data, and the weighted participants were 52,501,159. The weighted prevalence of depression was higher in females, which took up 65.85% of all depression patients. In fully adjusted models, sufficient volume of RPA was associated with lower depression risks, with OR (95% CI) =0.678 (0.520, 0.883). Further analysis revealed a U-shaped association between RPA and incident depression, and the inflection point was 640 MET-minutes/week. When RPA <640 MET-minutes/week, increased RPA was associated with lower risk of incident depression, with OR (95% CI) = 0.891 (0.834, 0.953). When RPA ≥ 640 MET-minutes/week, the benefits of RPA seemed to be not significant, with OR (95% CI) = 0.999 (0.990, 1.009).ConclusionOur findings observed associations between RPA condition and incident depression in the short sleep population. Moderate RPA was beneficial to maintain mental health and associated with lower incidence of depression for short sleepers, but excessive RPA might increase the risk of depression. For general short sleepers, keeping the RPA volume approximately 640 MET-minutes/week was beneficial to lower risks of depression. Gender difference should be considered as an important factor for further studies to examine these relationships and explore mechanisms.

Project description:BackgroundThe availability of outdoor recreational facilities is associated with increased leisure-time physical activity (PA). We investigated how much of this association is attributable to selection effects, and explored whether usage of recreational facilities was an explanatory mechanism.MethodsWe analysed data from 5199 participants in the SPOTLIGHT survey residing in five European urban regions. Adults completed a survey and a Google Street View-based virtual audit was conducted to objectively measure the availability of outdoor recreational facilities in the residential neighbourhood. We used negative binomial GEE models to examine the association between objective and subjective availability of outdoor recreational facilities and leisure-time PA, and explored whether this association was attenuated after adjustment for socioeconomic status and preference for neighbourhoods with recreational facilities (as indicators of self-selection). We examined whether reported use of recreational facilities was associated with leisure-time PA (as explanatory mechanism), and summarized the most important motivations for (not) using recreational facilities.ResultsSubjective - but not objective - availability of outdoor recreational facilities was associated with higher levels of total leisure-time PA. After adjustment for self-selection (which attenuated the association by 25%), we found a 25% difference in weekly minutes of total leisure-time PA between individuals with and without self-reported availability of outdoor recreational facilities. For our study population, this translates to about 28 min per week. Participants who reported outdoor recreational facilities to be present but indicated not to use them (RR = 1.19, 95% CI = 1.03;1.22), and those reporting outdoor recreational facilities to be present and to use them (RR = 1.33, 95% CI = 1.22, 1.45) had higher levels of total leisure-time PA than those who reported outdoor recreational facilities not to be present. Proximity to outdoor recreational facilities was the most important motivation for use.ConclusionThe modest attenuation in the association between availability of outdoor recreational facilities and self-reported leisure-time PA suggests that individuals' higher activity levels may be due more to the perceived availability of outdoor recreational facilities than to self-selection. The use of these facilities seemed to be an important underlying mechanism, and proximity was the main motivator for using recreational facilities.

Project description:ObjectiveExposure to per- and polyfluoroalkyl substances (PFAS) - endocrine disrupting chemicals - may increase cardiometabolic risk. We evaluated whether adolescent lifestyle factors modified associations between gestational PFAS exposure and cardiometabolic risk using a prospective cohort study.MethodsIn 166 mother-child pairs (HOME Study), we measured concentrations of four PFAS in maternal serum collected during pregnancy. When children were age 12 years, we calculated cardiometabolic risk scores from visceral adiposity area, blood pressure, and fasting serum biomarkers. We assessed adolescent physical activity and Healthy Eating Index scores using the Physical Activity Questionnaire for Older Children (PAQ-C), actigraphy, and 24-h diet recalls. Using multivariable linear regression and weighted quantile sum regression, we examined whether physical activity or diet modified covariate-adjusted associations of PFAS and their mixture with cardiometabolic risk scores.ResultsPhysical activity modified associations between perfluorooctanoic acid (PFOA) and cardiometabolic risk scores. Each doubling of PFOA was associated with worse cardiometabolic risk scores among children with PAQ-C scores < median (β:1.4; 95% CI:0.5, 2.2, n = 82), but not among those with PAQ-C scores ≥ median (β: 0.2; 95% CI: 1.2, 0.7, n = 84) (interaction p-value = 0.01). Associations were most prominent for insulin resistance, leptin-adiponectin ratio, and visceral fat area. We observed results suggesting that physical activity modified the association of PFAS mixture with cardiometabolic risk scores, insulin resistance, and visceral fat area (interaction p-values = 0.17, 0.07, and 0.10, respectively); however, the 95% CIs of the interaction terms included the null value. We observed similar, but attenuated patterns for PFOA and actigraphy-based measures of physical activity. Diet did not modify any associations. Physical activity or diet did not modify associations for other PFAS.ConclusionsChildhood physical activity modified associations of prenatal serum PFOA concentrations with children's cardiometabolic risk in this cohort, indicating that lifestyle interventions may ameliorate the adverse effects of PFOA exposure.

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Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.

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Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.

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