The effects of serum from prostate cancer patients with elevated body mass index on prostate cancer cells in vitro.
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ABSTRACT:
SUBMITTER: Mora BC
PROVIDER: S-EPMC4404997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:We examined the association between obesity and prostate cancer based on both body mass index (BMI) and waist circumference (WC) using the National Health Insurance System (NHIS) database for the entire male population of Korea. METHODS:A total of 1,917,430 men who underwent at least one health examination in 2009 without a previous diagnosis of any other cancer were tracked through December 2015. The hazard ratio (HR) and 95% confidence interval (CI) value for the association between prostate cancer and obesity were analyzed using multiple Cox regression model. Since there was a statistically significant interaction between WC and BMI, a multiple HR for prostate cancer was estimated with stratifying both WC and BMI to control the interaction between WC and BMI. RESULTS:Without considering WC as an adjustment factor, very weak association between BMI and prostate cancer development risk was observed. When WC was considered as an adjustment factor, no significant change in the HRs for prostate cancer development beyond the reference BMI was observed in the group with WC?<?85?cm in the multivariable-adjusted models. However, in the group with WC???85?cm, the HRs for prostate cancer increased as the BMI increased beyond the reference BMI. In addition, there was a discrepancy in the trend of prostate cancer development according to BMI among the groups with different categories for WC. CONCLUSION:In groups with abdominal obesity, a significant linear relationship was observed between increasing BMI and prostate cancer risk. Higher the WC category, the stronger was the association with BMI, signifying that the association of BMI with risk of prostate cancer development depends on abdominal obesity.
| S-EPMC7313154 | biostudies-literature
Project description:RationaleObesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity.MethodsWe used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate.ResultsThis cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m2. The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of -0.03 mmol/L in bicarbonate for each 1 kg/m2 increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status.ConclusionContrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.
| S-EPMC10512520 | biostudies-literature
Project description:Aging human males display reduced reproductive health, however testis aging is poorly understood at the molecular and genomic level. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men (>60 years old) – and examined age-related changes in germline development and in the somatic niche. Interestingly, age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and the somatic niche ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older, but not younger men. Taken together, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging, and their exacerbation by concurrent chronic conditions such as obesity.
2022-05-05 | GSE182786 | GEO
Project description:BackgroundProstate cancer aetiology is poorly understood. It may have origins early in life; previously we found a positive association with childhood height. The effects of early life body mass index (BMI; kg m(-2)) on prostate cancer remain equivocal. We investigated if childhood BMI, independently and adjusted for height, is positively associated with adult prostate cancer.MethodsSubjects were a cohort of 125208 boys formed from the Copenhagen School Health Records Register, born 1930-1969 with height and weight measurements at 7-13 years. Cases were identified through linkage to the Danish Cancer Registry. Cox proportional hazards regressions were performed.ResultsOverall, 3355 men were diagnosed with prostate cancer. Body mass index during childhood was positively associated with adult prostate cancer. The hazard ratio of prostate cancer was 1.06 (95% confidence interval (CI): 1.01-1.10) per BMI z-score at age 7, and 1.05 (95% CI: 1.01-1.10) per BMI z-score at age 13. Estimates were similar and significant at all other ages. However, adjustment for childhood height attenuated the associations at all but the youngest ages as most estimates became nonsignificant.ConclusionsThese results suggest that at most childhood ages, BMI does not confer an additional risk for prostate cancer beyond that of height.
| S-EPMC4090733 | biostudies-literature
Project description:BackgroundTriclosan-a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies-has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.MethodsWe investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003-2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures-either presence vs. absence or quartiles of triclosan-we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.ResultsCompared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.ConclusionsTriclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.
| S-EPMC3836985 | biostudies-literature
Project description:PurposeThe relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA.MethodsWe searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome.ResultsIn the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations.ConclusionThere is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.
| S-EPMC7105428 | biostudies-literature
Project description:PurposeFatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI).MethodsIn a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R(2) > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909).ResultsFour of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (P(interaction) = .004) and PCa mortality (P(interaction) = .056). Among overweight men (BMI > or = 25 kg/m(2)), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (P(interaction) = .02).ConclusionFASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men.
| S-EPMC2940394 | biostudies-literature
Project description:BackgroundTo investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.MethodsFour polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or > or = 30 kg/m2, respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression.ResultsCompared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, Ptrend = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9).ConclusionOur results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.
| S-EPMC2640369 | biostudies-literature
Project description:We investigated the relationship between the body mass index (BMI) trajectory across childhood and the subsequent occurrence of elevated blood pressure (BP) in the Chinese pediatric population. The study cohort from the China Health and Nutrition Survey comprised 1484 children, each of whom underwent three BP and BMI assessments during childhood and had a non-elevated BP during the first childhood assessment. A group-based trajectory model was used to identify four distinct BMI trajectories across childhood: lean-stable increase, medium-marked increase, heavy marked decrease, and heavy marked increase. Elevated BP in childhood was as defined in the China's national BP reference for children. Covariate-adjusted logistic regression models were used to assess the associations of BMI trajectories with elevated BP. Overall, 27.6% of all participants between 3 and 13 years of age during the first childhood assessment developed elevated BP during a mean 6.5-year follow-up. Compared with participants in the lean-stable increase group, those in the medium-marked increase and heavy marked increase groups were more likely to have elevated BP (odds ratio [95% confidence interval], OR [95% CI]: 1.46 [1.08, 1.96] and 5.29 [2.44, 11.48], respectively; Ps < .05). The OR for the heavy marked decrease group was not statistically significant (OR [95% CI]: 1.58 [0.80, 3.13]; P = .192). In summary, distinct BMI trajectories conferred significantly different odds of elevated BP upon children, thus underscoring the importance of weight management in early life.
| S-EPMC8029666 | biostudies-literature
Project description:PurposeThe purpose of this work is to describe the association between body mass index (BMI) and (1) management option for localized prostate cancer (PCa) and (2) disease-specific quality of life (ds-QoL) after treatment or active surveillance.Subjects/patients and methodsWe analysed data from men with localized PCa managed with radical prostatectomy (RP), radiation therapy (RT), or active surveillance (AS) in a prospective, population-based cohort study. We evaluated the association between BMI and management option with multivariable multinomial logistic regression analysis. The association between BMI and ds-QoL was assessed using multivariable longitudinal linear regression. Regression models were adjusted for baseline domain scores, demographics, and clinicopathologic characteristics.ResultsA total of 2378 men were included (medians [quartiles]: age 64 [59-69] years; BMI 27 kg/m2; 77% were non-Hispanic white); 29% were obese (BMI ≥ 30). Accounting for demographic and clinicopathologic features, BMI ≥ 28 kg/m2 was inversely associated with the likelihood of receiving RP (compared with RT) and became statistically significant at BMI ≥ 33 kg/m2 (maximum adjusted relative risk ratio = 0.80, 95% CI 0.67 to 0.95, p = 0.013 for BMI ≥ 33 vs. 25). Conversely, BMI was not significantly associated with the likelihood of receiving AS compared with RT. After stratification by management option, obese men who underwent definitive treatment were not found to have clinically worse ds-QoL. Obese men initially on AS appeared to have worse urinary incontinence than nonobese men, but this was not significant on an as-treated sensitivity analysis.ConclusionsAmong men with localized PCa, those with BMI ≥ 33 kg/m2 were less likely to receive surgery than radiation. Obesity was not associated with ds-QoL in men undergoing definitive treatment, nor in men who remained on AS.
| S-EPMC9931544 | biostudies-literature