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Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

ABSTRACT: BACKGROUND:Adult body size is related to ovarian cancer risks, but size in childhood may also influence risks. We investigated if childhood body mass index (kg/m2), height, and growth patterns were associated with ovarian cancer overall and by histologic subtypes, including effects of birthweight. METHODS:A cohort of 155,958 girls from the Copenhagen School Health Records Register, born 1930 to 1989 with measured weights and heights from 7 to 13 years, were included. During follow-up, 1,041 ovarian cancers were recorded. Overweight was defined using International Obesity Task Force criteria. Cox regressions were performed. RESULTS:Compared with non-overweight girls, at most ages girls with overweight had increased risks of ovarian cancer overall (HR range: 1.24-1.34), mucinous, endometrioid, and clear cell ovarian cancers, but not serous and other ovarian cancers. Childhood height had positive and significant associations with ovarian cancer overall (HR range: 1.07-1.10 per z-score) and the endometrioid subtype but not with the other subtypes. Adjusting for birthweight minimally altered the associations with childhood body size. In growth analyses, girls with overweight or who were tall at 7 and 13 years had increased risks of ovarian cancer overall compared with average-sized girls at both ages. CONCLUSIONS:Ovarian carcinogenesis is linked to childhood overweight, tallness, and growth, with variations across histological subtypes, suggesting that early life plays a role in the origins of this disease. IMPACT:These findings emphasize that healthy body size and growth during childhood are important as they may contribute to reducing ovarian cancer risks.

SUBMITTER: Aarestrup J

PROVIDER: S-EPMC6325003 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

Aarestrup Julie J Trabert Britton B Ulrich Lian G LG Wentzensen Nicolas N Sørensen Thorkild I A TIA Baker Jennifer L JL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180927 1

<h4>Background</h4>Adult body size is related to ovarian cancer risks, but size in childhood may also influence risks. We investigated if childhood body mass index (kg/m<sup>2</sup>), height, and growth patterns were associated with ovarian cancer overall and by histologic subtypes, including effects of birthweight.<h4>Methods</h4>A cohort of 155,958 girls from the Copenhagen School Health Records Register, born 1930 to 1989 with measured weights and heights from 7 to 13 years, were included. Du ...[more]

PMID: 30262600

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Project description:IntroductionMetabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts.MethodsUntargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth.ResultsIn the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 × 10-3). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 × 10-6) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 × 10-3) with overweight after FDR correction.ConclusionThe metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories.

Project description:ObjectiveThis prospective cohort study was aimed at investigating the associations between cord blood metabolic factors and early-childhood growth, further elucidating the relationships between cord blood metabolites and overweight and obesity in early life.MethodsA total of 2,267 pairs of mothers and offspring were recruited in our study. Cord blood plasma was assayed for triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), C-peptide, insulin, and glycosylated hemoglobin type A1C (HbA1c) levels. Data of anthropometric measurements were collected from offspring at birth, 6 months, 12 months, and 18 months. Multiple linear regression models were used to evaluate the correlations between cord blood metabolic factors and weight Z-scores, body mass index (BMI) Z-scores, and weight gains at the early stage of life. Forward stepwise logistic regression analyses were applied to explore the associations between cord blood metabolic factors and early-childhood overweight and obesity. Receiver operating characteristic (ROC) curve analyses were applied to determine the optimal cutoff points for cord blood metabolic factors in predicting early-childhood overweight and obesity.ResultsAfter adjustments for covariates, cord blood TG concentrations and TG/TC ratios were negatively associated with weight Z-scores from birth to 18 months. Cord blood C-peptide and HbA1c levels were inversely associated with weight Z-scores at 6 months and 18 months. Cord blood TG concentrations and TG/TC ratios were negatively correlated with BMI Z-scores up to 18 months. Cord blood C-peptide levels and HbA1c levels were inversely correlated with BMI Z-scores at 18 months. Cord blood TG, TG/TC ratios, C-peptide, and HbA1c had negative correlations with weight gains from birth to 6 months, but the correlations attenuated as time went on. Increase in cord blood TG and HbA1c levels and TG/TC ratios were significantly associated with decreased risks of overweight and obesity at 6 months, 12 months, and 18 months.ConclusionsCord blood metabolic factors were significantly associated with early-childhood growth patterns.

Project description:BackgroundThere is an increasing focus on the first 1000 days from conception to two years of age as a period of importance for future weight. We aimed to describe the interaction between fetal and infant growth and their association with and ability to predict childhood overweight.MethodsWe used routinely collected fetal growth data from Aarhus University Hospital and child growth data from Aarhus Municipality, 2008-2018. The outcome was overweight at age 5-9 years. The fetal growth rates at weeks 28 and 34 were extracted from individual trajectories using mixed models. We identified patterns of infant BMI Z-score growth using latent class analysis and estimated odds ratios of overweight at age 5-9 years dependent on fetal and infant growth. Predictive capabilities were assessed by comparing areas under the ROC-curves (AUCROC) of the prediction models.ResultsIn 6206 children, we identified three infancy growth patterns: average, accelerated, and decelerated growth. We found 1.09 (95% CI: 1.06-1.12) greater odds of being overweight for every 10 g/week increase in fetal growth rate at week 34. Compared with average growth, accelerated infant growth was associated with 1.52 (95% CI: 1.20-1.90) greater odds of overweight. Combining fetal and infant growth, children with average fetal growth and accelerated infant growth had 1.96 (95% CI: 1.41-2.73) greater odds of overweight. Fast fetal growth with decelerated infant growth was not associated with being overweight (OR: 0.79 (95% CI: 0.63-0.98)), showing that infant growth modified the association between fetal growth and overweight. When fetal growth was added to a prediction model containing known risk factors, the AUCROC remained unchanged but infant growth improved the predictive capability (AUCROC difference: 0.04 (95% CI: 0.03-0.06)).ConclusionFetal and infant growth were independently associated with overweight, but distinct combinations of fetal and infant growth showed marked differences in risk. Infant, but not fetal, growth improved a prediction model containing known confounders.

Project description:BackgroundEpithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy with limited treatment options. CD47 is a critical immune checkpoint for tumor immune evasion and has been targeted in various clinical trials. This study aimed to assess the impact of chemotherapy on CD47 expression in EOC in order to determine the potential and optimal timing of CD47-targeted therapy in ovarian cancer. We analyzed the expression of CD47 in ovarian cancer and the effect of chemotherapy on the expression of CD47 in ovarian cancer tissues. Furthermore, we investigated the effect of chemotherapy on the expression of CD47 in ovarian cancer cells.MethodsCD47 expression was examined using immunohistochemistry (IHC) of specimens from 78 patients with EOC who underwent neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) with paired tissue specimens obtained before and after NACT. A retrospective review of the medical records was conducted to correlate demographic and survival data. Subsequently, we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry analysis to examine and compare CD47 expression across human ovarian surface epithelial cell line (HOSE), SKOV3, and ES2 cells and to characterize the changes in CD47 expression in SKOV3 and ES2 cells after cisplatin treatment.ResultsCD47 expression was observed in 63 out of 78 (80.8%) cases before NACT. The expression of CD47 was not associated with the clinicopathological characteristics or the prognosis of patients with EOC. After three cancer specimens were excluded due to the absence of cancer cells following NACT, Wilcoxon exact tests of 75 pairs of matched specimens indicated that the expression of CD47 increased after chemotherapy (P=0.006). CD47 was expressed at varying levels in HOSE ovarian epithelial cells and SKOV3 and ES2 ovarian cancer cells. Notably, the CD47 messenger RNA (mRNA) expression of HOSE cells was observed to be lower than that of the SKOV3 and ES2 ovarian cancer cells (P<0.001). Following treatment with cisplatin, RT-qPCR indicated an increase in CD47 mRNA expression in SKOV3 and ES2 cells (P<0.001). Flow cytometry revealed a notable elevation in the cell surface CD47 protein mean fluorescence intensity of cisplatin-treated SKOV3 and ES2 cells (P<0.001).ConclusionsCD47 is highly expressed in ovarian cancer, and NACT increases the expression of CD47, which may contribute to tumor immune evasion. It is possible that platinum-based chemotherapy may result in elevated CD47 mRNA expression and cell surface CD47 protein expression.

Dataset Information

Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

Publications

Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

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