Childhood height and risk of testicular germ cell tumors in adulthood.
ABSTRACT: Increased adult stature has been associated with risk of testicular germ cell tumors (TGCT) in a number of studies. Whether childhood stature is also associated with TGCT is unclear as no studies of measured childhood height and TGCT have been reported. Thus, associations between TGCT in adulthood and childhood height and growth between ages 7 and 13 years were examined in a cohort from the Copenhagen School Health Records Register. Analyses included 162,607 boys born during the years 1930-1989. Development of TGCT was determined via linkage to the Danish Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Between 1968 and 2014, 782 TGCT were diagnosed. Childhood height, per one unit increase in z-score, was associated with risk of TGCT, with HRs ranging from 1.11 (95%CI 1.03-1.20) at age 7 to 1.09 (95%CI?=?1.01-1.18) at age 13. In a categorical analysis, the shortest boys were at the lowest risk of developing TGCT. Results varied little by TGCT histology (seminoma and nonseminoma). Growth between ages 7 and 13 years was not associated with risk. These findings suggest that risk of TGCT in adulthood was already determined by age 7 years. Although the mechanism requires further investigation, these results provide additional evidence that risk of TGCT is determined at a young age, thus suggesting that additional investigation of early life factors is warranted.
Project description:BACKGROUND:Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR). METHODS:The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights-measured between ages 7 and 13 years-were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS:There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk. CONCLUSIONS:The association between childhood height and prostate cancer risk was driven by height at age 13 years. IMPACT:Our findings implicate late childhood, adolescence, and adulthood growth periods as containing the exposure window(s) of interest that underlies the association between height and prostate cancer. The causal factor may not be singular given the complexity of both human growth and carcinogenesis.
Project description:To estimate differences in skeletal maturity and stature from birth to age 18 years between individuals who are overweight vs normal weight in young adulthood.Weight, length and height, and relative skeletal age (skeletal-chronological age) were assessed annually from birth to age 18 years in 521 subjects (255 women) in the Fels Longitudinal Study who were overweight or obese (body mass index (BMI) >25 kg?m(-2), n=131) or normal weight (n=390) in young adulthood (18-30 years). Generalized estimating equations were used to test for skeletal maturity and stature differences by young adult BMI status.Differences in height increased during puberty, being significant for girls at ages 10 to 12 years, and for boys at ages 11 to 13 years (P-values<0.001), with overweight or obese adults being ?3 cm taller at those ages than normal weight adults. These differences then diminished so that by age 18 years, overweight or obese adults were not significantly different in stature to their normal weight peers. Differences in skeletal maturity were similar, but more pervasive; overweight or obese adults were more skeletally advanced throughout childhood. Skeletal maturity differences peaked at chronological age 12 in boys and 14 in girls (P-values<0.001), with overweight or obese adults being ?1 year more advanced than normal weight adults.This descriptive study is the first to track advanced skeletal maturity and linear growth acceleration throughout infancy, childhood and adolescence in individuals who become overweight, showing that differences occur primarily around the time of the pubertal growth spurt. Increased BMI in children on a path to becoming overweight adults precedes an advancement in skeletal development and subsequently tall stature during puberty. Further work is required to assess the predictive value of accelerated pubertal height growth for assessing obesity risk in a variety of populations.
Project description:Taller stature and obesity in adulthood have been consistently associated with an increased risk of thyroid cancer, but few studies have investigated the role of childhood body size. Using data from a large prospective cohort, we examined associations for height and body mass index (BMI) at ages 7 to 13 years with risk of thyroid cancer in later life. The study population included 321,085 children from the Copenhagen School Health Records Register, born between 1930 and 1989 in Copenhagen, Denmark, with measurements of height and weight from 7 to 13 years of age. These data were linked with the Danish Cancer Registry to identify incident thyroid cancer cases (1968-2010). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for age- and sex-specific height and BMI SD scores (SDS) using proportional hazards models stratified by birth cohort and sex. During follow-up (median = 38.6 years), 171 women and 64 men were diagnosed with thyroid cancer. Both height and BMI were positively associated with thyroid cancer risk, and these associations were similar by age at measurement. Using age 10 as an example, HRs per 1 unit increase in SDS for height (~6-7 cm) and BMI (~1.5-2 kg/m(2)) were 1.22 (95% CI, 1.07-1.40) and 1.15 (95% CI, 1.00-1.34), respectively. These results, together with the relatively young ages at which thyroid cancers are diagnosed compared with other malignancies, suggest a potential link between early-life factors related to growth and body weight and thyroid carcinogenesis.
Project description:Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life.We assessed associations between childhood body mass index (BMI) and height-measured annually between ages 7 and 13-with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255?053 children born during 1930-1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression.During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages.Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.
Project description:<h4>Background</h4>Short stature or short legs is associated with cardiometabolic disease. Few studies have addressed this issue in children, incorporated repeated measures, or studied modern cohorts.<h4>Methods</h4>We examined if change in total height, leg length and trunk length between two time points from early (median: 3.2 years) to mid-childhood (median: 7.7 years), with and without adjustment for concurrent change in adiposity (subscapular plus triceps skinfold thickness), was associated with mid-childhood cardiometabolic risk in 315 boys and 295 girls from Project Viva. The main outcome was a cardiometabolic risk score based on sex-specific internal z-scores for systolic blood pressure, waist circumference, homeostatic model assessment of insulin resistance, triglycerides and high-density lipoprotein-cholesterol.<h4>Results</h4>Mean (SD) total height was 97.9 (4.5) cm in boys and 97.1 (4.7) cm in girls in early childhood and 129.1 (7.2) cm in boys and 128.3 (7.9) cm in girls in mid-childhood. Trunk length constituted about half of total height. In linear regression models adjusted for parental anthropometry and socio-demographics, faster growth in total height, leg length and particularly trunk length, were associated with higher cardiometabolic risk in mid-childhood. Per 1 cm annual increase in trunk length, the cardiometabolic risk score was 0.23 z-score (95% confidence interval [CI] 0.08, 0.39) higher among boys and 0.47 z-score (95% CI 0.33, 0.60) higher among girls. Estimates were attenuated after adjusting for adiposity (boys: 0.03 z-score, 95% CI -0.11, 0.18; girls: 0.32 z-score, 95% CI 0.19, 0.45).<h4>Conclusion</h4>Rapid linear growth, particularly in trunk length, was associated with higher cardiometabolic risk in childhood, which was explained by relationships of linear growth with adiposity in boys, but only partly in girls.
Project description:<h4>Background</h4>Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg?m(-2)) and height were associated with histologic subtypes of endometrial cancer.<h4>Methods</h4>From the Copenhagen School Health Records Register, 155?505 girls born 1930-1989 with measured weights and heights from 7 to 13 years were linked to health registers. BMI and height were transformed to age-specific z-scores. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox regressions.<h4>Results</h4>A total of 1020 endometrial cancers were recorded. BMI was non-linearly associated with all endometrial cancers, oestrogen-dependent cancers and the subtype of endometrioid adenocarcinomas; associations were statistically significant and positive above a z-score=0 and non-significant below zero. Compared with a 7-year-old girl with a BMI z-score=0, an equally tall girl who was 3.6?kg heavier (BMI z-score=1.5) had a hazard ratio=1.53 (95% confidence interval: 1.29-1.82) for endometrioid adenocarcinoma. BMI was not associated with non-oestrogen-dependent cancers, except at the oldest childhood ages. Height at all ages was statistically significant and positively associated with all endometrial cancers, except non-oestrogen-dependent cancers. At 7 years, per ~5.2?cm (1 z-score), the risk of endometrioid adenocarcinoma was 1.18 (95% confidence interval: 1.09-1.28). Among non-users of unopposed oestrogens, associations between BMI and endometrioid adenocarcinoma strengthened, but no effects on height associations were observed.<h4>Conclusions</h4>Endometrial carcinogenesis is linked to early-life body size, suggesting that childhood BMI and height may be useful indicators for the risk of later development of endometrial cancer and might aid in the early prevention of obesity-related endometrial cancers.
Project description:Background:Low bone mineral density and an increased risk of appendicular and vertebral fractures are well-established consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment. Monitoring of endocrine and skeletal health and timely intervention in at-risk patients is important in the management of children with DMD. Methods:As part of the Norwegian Duchenne muscular dystrophy cohort study, we examined the skeletal maturation of 62 boys less than 18?years old, both currently glucocorticoid treated (n?=?44), previously treated (n?=?6) and naïve (n?=?12). The relationship between bone age, height and bone mineral density (BMD) Z-scores was explored. Results:The participants in the glucocorticoid treated group were short in stature and puberty was delayed. Bone age was significantly delayed, and the delay increased with age and duration of treatment. The difference in height between glucocorticoid treated and naïve boys was no longer significant when height was corrected for delayed skeletal maturation. Mean BMD Z-scores fell below -?2 before 12?years of age in the glucocorticoid treated group, with scores significantly correlated with age, duration of treatment and pubertal development. When BMD Z-scores were corrected for by retarded bone age, the increase in BMD Z-scores was significant for all age groups. Conclusion:Our results suggest that skeletal maturation should be assessed in the evaluation of short stature and bone health in GC treated boys with DMD, as failing to consider delayed bone age leads to underestimation of BMD Z-scores and potentially overestimation of fracture risk.
Project description:Background:Excess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer. Objective:To examine if childhood body mass index (BMI; kg/m2) and height are associated with pancreatic cancer in adult life. Methods:We linked 293,208 children born from 1930-1982 in the Copenhagen School Health Records Register who had measured values of weights and heights at ages 7-13 years with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions. Results:During 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were positively and significantly associated with pancreatic cancer in men and women up to age 70 years; beyond age 70 the associations diminished. The HRs of pancreatic cancer were 1.13 (95% CI: 1.05-1.21) and 1.18 (95% CI: 1.09-1.27) per BMI z-score at ages 7 and 13 years, respectively. A BMI ?1.5 z-score at ages 7, 10 and 13 years was positively and significantly associated with pancreatic cancer; however, the effect did not differ from having a BMI z-score ?1.5 at only one of these ages. Positive, albeit non-statistically significant, associations were identified with height. Conclusions:BMI at all ages from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic cancer in adults.
Project description:Predicted maturity offset and age at peak height velocity are increasingly used with youth athletes, although validation studies of the equations indicated major limitations. The equations have since been modified and simplified.The objective of this study was to validate the new maturity offset prediction equations in independent longitudinal samples of boys and girls.Two new equations for boys with chronological age and sitting height and chronological age and stature as predictors, and one equation for girls with chronological age and stature as predictors were evaluated in serial data from the Wroc?aw Growth Study, 193 boys (aged 8-18 years) and 198 girls (aged 8-16 years). Observed age at peak height velocity for each youth was estimated with the Preece-Baines Model 1. The original prediction equations were included for comparison. Predicted age at peak height velocity was the difference between chronological age at prediction and maturity offset.Predicted ages at peak height velocity with the new equations approximated observed ages at peak height velocity in average maturing boys near the time of peak height velocity; a corresponding window for average maturing girls was not apparent. Compared with observed age at peak height velocity, predicted ages at peak height velocity with the new and original equations were consistently later in early maturing youth and earlier in late maturing youth of both sexes. Predicted ages at peak height velocity with the new equations had reduced variation compared with the original equations and especially observed ages at peak height velocity. Intra-individual variation in predicted ages at peak height velocity with all equations was considerable.The new equations are useful for average maturing boys close to the time of peak height velocity; there does not appear to be a clear window for average maturing girls. The new and original equations have major limitations with early and late maturing boys and girls.
Project description:BACKGROUND: Prostate 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. METHODS: Subjects 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. RESULTS: Overall, 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. CONCLUSIONS: These results suggest that at most childhood ages, BMI does not confer an additional risk for prostate cancer beyond that of height.