Is the association of birth weight with premenopausal breast cancer risk mediated through childhood growth?
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ABSTRACT:
SUBMITTER: dos Santos Silva I
PROVIDER: S-EPMC2409836 | biostudies-other | 2004 Aug
REPOSITORIES: biostudies-other
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Project description:Maternal smoking during pregnancy is associated with both reduced birth weight and adverse neurobehavioral outcomes. The aim of this study was to investigate longitudinal associations between maternal smoking during pregnancy and childhood behavioral outcomes, and to determine the role of birth weight in mediating such associations. The study included 489 mother-child pairs. Prenatal exposures were assessed via maternal interviews conducted on average 1 year after delivery and child behavior assessments were completed at 5-12 years of age using the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF). Maternal smoking during pregnancy was associated with externalizing and total behavior problems according to both mother and teacher report. Maternal smoking was also associated with the following percentage increases in scores: 41% (CBCL) and 44% (TRF) for aggressive behavior and 65% (CBCL) and 47% (TRF) for attention problems. Associations with behavior problems were attenuated or no longer observed for mothers that quit smoking in early pregnancy. The proportion of the total effect of maternal smoking on behavioral outcomes explained by differences in birth weight was small and ranged from 6.6% for externalizing behavior on the CBCL to 20.1% for rule-breaking behavior on the CBCL. Our results suggest that birth weight differences explain only a small proportion of the magnitude of association between maternal smoking during pregnancy and selected behavioral outcomes.
| S-EPMC6734934 | biostudies-literature
Project description:ImportanceThere is a lack of evidence on the association of birth weight, childhood body mass index (BMI), change in BMI during childhood, and childhood height with subsequent risks of hidradenitis suppurativa (HS) in adulthood.ObjectiveTo investigate the association of birth weight, childhood BMI, change in BMI during childhood, and childhood height with subsequent risks of HS in adulthood in a large Danish population-based cohort.Design, setting, and participantsThis cohort study included 347 200 schoolchildren from the Copenhagen School Health Records Register born from 1930 to 1996 who were linked to the Danish National Patient Register of hospital discharge diagnoses to identify cases of HS. Birth weight was reported by parents or guardians, whereas childhood weight and height were measured by school physicians or nurses at ages 7 through 13 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs. Statistical analysis was performed from February 20, 2019, to May 15, 2019.Main outcomes and measuresA diagnosis of HS as recorded in the Danish National Patient Register.ResultsAmong the 347 200 children included in the study (175 750 boys) during the follow-up period from 1977 to 2017, 1037 individuals (677 females; median age at diagnosis, 39 years [range, 15-73 years]) received a diagnosis of HS. A nonlinear (U-shaped) association was found between birth weight and HS, such that both the lightest (2.00-2.75 kg; HR, 1.36 [95% CI, 1.10-1.68]) and the heaviest babies (4.26-5.50 kg; HR, 1.39 [95% CI, 1.01-1.93]) had increased risks of HS compared with normal-weight babies (3.26-3.75 kg; P = .04 for deviation from linearity). The risk of HS increased significantly with increasing BMI z score at each age from 7 to 13 years, from an HR of 1.32 (95% CI, 1.24-1.40) per BMI z score at 7 years of age to an HR of 1.50 (95% CI, 1.40-1.61) per BMI z score at 13 years of age. Compared with children with a normal weight at 7 and 13 years of age, those with a normal weight at 7 years of age and overweight at 13 years of age had a significantly increased risk of HS (HR, 2.11 [95% CI, 1.63-2.74]) and children with persistent overweight at both ages also had an increased risk of HS (HR, 2.61 [95% CI, 2.02-3.38]). Children with overweight at 7 years of age but with normal weight at 13 years of age did not have a significantly increased risk of HS (HR, 1.05 [95% CI, 0.67-1.67]). Childhood height at all ages was not associated with risk of HS (children at 7 years had an HR of 1.00 [95% CI, 0.94-1.07], and those 13 years had an HR of 1.06 [95% CI, 0.99-1.13], per z score).Conclusions and relevanceThis cohort study found that both the lightest and heaviest babies had increased risks of HS. Childhood BMI was positively and significantly associated with risk of HS development in adulthood. These findings suggest that returning to normal weight before puberty reduces risks of HS to levels observed in children who were never overweight. Childhood height was not associated with risk of HS.
| S-EPMC7191432 | biostudies-literature
Project description:Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P?<?5?×?10-8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio?=?0.86 per 500 g higher BW; 95% confidence interval 0.73-1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer, but we are unable to rule out an association between the non-genetically-determined component of BW and breast cancer. Thus, genetically-predicted higher BW was not associated with an increased risk of breast cancer in adult life in our MR study.
| S-EPMC6497616 | biostudies-literature
Project description:Few studies have investigated the association between the full range of birth weight and the risk of childhood obesity in high-, middle- and low-income countries. The aim of the present study is to assess the association between different levels of birth weight and the risk of obesity among children aged 9-11 years in 12 countries.A multinational, cross-sectional study of 5141 children aged 9-11 years was conducted in 12 countries. Height and weight were obtained using standardized methods. Time spent in moderate-to-vigorous physical activity (MVPA), sedentary and sleeping were objectively measured using 24-h, waist-worn accelerometer (Actigraph GT3X+) monitored for 7 days. Birth weight and other factors (regions, parental education, maternal history of gestational diabetes, children age, gender, breast feeding, gestational age, unhealthy diet scores and healthy diet scores) were collected by parental and children's questionnaires. Multilevel modeling was used to account for the nested nature of the data.The overall prevalence of obesity (BMI z-score>+2 s.d.) was 15.4% for boys and 10.0% for girls. There was a positive association between birth weight and BMI z-scores. The multivariable-adjusted odds ratios (ORs) of childhood obesity were significantly higher among children whose birth weights were 3500-3999 g (OR 1.45; 95% confidence interval (CI): 1.10-1.92), and >4000 g (OR 2.08; 95% CI: 1.47-2.93), compared with the reference group (2500-2999 g). The positive association between birth weight and the odds of childhood obesity was seen in girls, whereas a U-shaped association appeared in boys.High levels of birth weight, defined as birth weight ⩾3500 g, were associated with increased odds of obesity among 9-11-year-old children in 12 countries. However, sex differences in the association between birth weight and the risk of obesity need to be considered when planning interventions to reduce childhood obesity.
| S-EPMC4850624 | biostudies-other
Project description:GWAS identified variants associated with birth weight (BW), childhood obesity (CO) and childhood BMI (CBMI), and placenta is a critical organ for fetal development and postnatal health. We examined the role of placental transcriptome and eQTLs in mediating the genetic causes for BW, CO and CBMI, and applied integrative analysis (Colocalization and MetaXcan). GWAS loci associated with BW, CO, and CBMI were substantially enriched for placenta eQTLs (6.76, 4.83 and 2.26 folds, respectively). Importantly, compared to eQTLs of adult tissues, only placental eQTLs contribute significantly to both anthropometry outcomes at birth (BW) and childhood phenotypes (CO/CBMI). Eight, six and one transcripts colocalized with BW, CO and CBMI risk loci, respectively. Our study reveals that placental transcription in utero likely plays a key role in determining postnatal body size, and as such may hold new possibilities for therapeutic interventions to prevent childhood obesity.
| S-EPMC6329610 | biostudies-literature
Project description:BackgroundBirth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations.MethodsWe used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels.FindingsBW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (βadj [95% CI per SD] for obesity: -0.12 [-0.15, -0.08]; normal weight: -0.04 [-0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: -0.11 [-0.14, -0.08]; normal weight: -0.02 [-0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: -0.12 [-0.16, -0.08]; normal weight: -0.06 [-0.11, -0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05).InterpretationWe identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD.FundingNovo Nordisk Foundation (NNF15OC0016544, NNF0064142 to T.H., NNF15OC0016692 to T.H. and A.K., NNF18CC0033668 to S.E.S, NNF18SA0034956 to C.E.F., NNF20SA0067242 to DCA, NNF18CC0034900 to NNF CBMR), The Innovation Fund Denmark (0603-00484B to T.H.), The Danish Cardiovascular Academy (DCA) and the Danish Heart Foundation (HF) (PhD2021007-DCA to P.K.R, 18-R125-A8447-22088 (HF) and 21-R149-A10071-22193 (HF) to M.A.V.L., PhD2023009-HF to L.A.H), EU Horizon (668031, 847989, 825694, 964590 to A.K.), Innovative Health Initiative (101132901 for A.K.), A.P. Møller Foundation (19-L-0366 to T.H.), The Danish National Research Foundation, Steno Diabetes Center Sjælland, and The Region Zealand and Southern Denmark Health Scientific Research Foundation.
| S-EPMC11293585 | biostudies-literature
Project description:ObjectiveTo confirm the previously reported increased risk of leukemia among macrosomic children (those with birth weight >4 kg).MethodsBirth certificates of Arizona, Illinois, and Kentucky children diagnosed as having acute lymphoblastic leukemia (ALL) before age 5 years were matched with birth certificates from leukemia-free children of the same sex, race, and ethnicity who were born in the same county on or about the same day. Odds ratios (ORs) for ALL among children of low (<2.5 kg) or high (>4 kg) birth weight were calculated by conditional logistic regression.ResultsChildren with high birth weight had an elevated risk of ALL in the first 5 years of life (OR 1.28, 95% confidence interval [CI] 1.01-1.61). The excess risk was confined to non-Hispanic whites (OR 1.77, 95% CI 1.27-2.48), both boys (OR 1.57, 95% CI 1.01-2.45) and girls (OR 2.10, 95% CI 1.26-3.52).ConclusionsThis study confirms the association between high birth weight and ALL previously reported by other studies in children of European ancestry. The literature on maternal risk factors for both macrosomia and ALL is reviewed, with maternal overnutrition emerging as a plausible risk factor for both outcomes.
| S-EPMC9310147 | biostudies-literature
Project description:Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
| S-EPMC7365745 | biostudies-literature
Project description:ImportanceThe association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation.ObjectiveTo investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics.Design, setting, and participantsThis multicenter analysis used pooled individual-level data from 758?592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13?082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017.ExposuresBody mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years.Main outcomes and measuresInvasive or in situ premenopausal breast cancer.ResultsAmong the 758?592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference,?0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI?35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall.Conclusions and relevanceThe results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.
| S-EPMC6248078 | biostudies-literature
Project description:Childhood obesity is a global public health problem. Understanding the molecular mechanisms that underlie early origins of childhood obesity can facilitate interventions. Consistent phenotypic and genetic correlations have been found between childhood obesity traits and birth weight (a proxy for in-utero growth), suggesting shared genetic influences (pleiotropy). We aimed to (1) investigate whether there is significant shared genetic influence between birth weight and childhood obesity traits, and (2) to identify genetic loci with shared effects. Using a statistical approach that integrates summary statistics and functional annotations for paired traits, we found strong evidence of pleiotropy (P < 3.53 × 10-127) and enrichment of functional annotations (P < 1.62 × 10-39) between birth weight and childhood body mass index (BMI)/obesity. The pleiotropic loci were enriched for regulatory features in skeletal muscle, adipose and brain tissues and in cell lines derived from blood lymphocytes. At 5% false discovery rate, 6 loci were associated with birth weight and childhood BMI and 13 loci were associated with birth weight and childhood obesity. Out of these 19 loci, one locus (EBF1) was novel to childhood obesity and one locus (LMBR1L) was novel to both birth weight and childhood BMI/obesity. These findings give evidence of substantial shared genetic effects in the regulation of both fetal growth and childhood obesity.
| S-EPMC7794220 | biostudies-literature