Birthweight, childhood body size, and timing of puberty and risks of breast cancer by menopausal status and tumor receptor subtypes.

BACKGROUND: Associations of birthweight, childhood body size and pubertal timing with breast cancer risks by menopausal status and tumor receptor subtypes are inconclusive. Thus, we investigated these associations in a population-based cohort of Danish women. METHODS: We studied 162,419 women born between 1930 and 1996 from the Copenhagen School Health Records Register. The register includes information on birthweight, measured childhood weights and heights at the age of 7-13 years, and computed ages at the onset of the growth spurt (OGS) and at peak height velocity (PHV). The Danish Breast Cancer Cooperative Group database provided information on breast cancer (n = 7510), including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and menopausal status. Hormone replacement therapy use came from the Danish National Prescription Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression. RESULTS: We found that birthweight was not associated with any breast cancer subtypes. While childhood BMI was not statistically significantly associated with ER+ tumors nor consistently with ER- tumors among pre-menopausal women, consistent inverse associations were found among postmenopausal women. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 0.90 (95% CI 0.87-0.93) and 0.84 (95% CI 0.79-0.91) per BMI z-score, respectively. Similarly, childhood BMI was inversely associated with pre- and postmenopausal HER2- tumors, but not with HER2+ tumors. Childhood height was positively associated with both pre- and postmenopausal ER+ tumors, but not with ER- tumors. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 1.09 (95% CI 1.06-1.12) and 1.02 (95% CI 0.96-1.09) per height z-score, respectively. In general, childhood height was positively associated with HER2+ and HER2- tumors among pre- and postmenopausal women. Ages at OGS and PHV were not associated with any breast cancer subtypes. CONCLUSIONS: We showed that a high BMI and short stature in childhood are associated with reduced risks of certain breast cancer subtypes. Thus, childhood body composition may play a role in the development of breast cancer.

Childhood body mass index trajectories and associations with adult-onset chronic kidney disease in Denmark: A population-based cohort study.

BACKGROUND: Although excess adult adiposity is a strong risk factor for chronic kidney disease (CKD), evidence for associations with early life body size is limited. We investigated whether childhood body mass index (BMI) trajectories are associated with adult-onset CKD and end-stage kidney disease (ESKD) using a population-based cohort. Further, we examined the role of adult-onset type 2 diabetes (T2D) in these associations. METHODS AND FINDINGS: We included 151,506 boys and 148,590 girls from the Copenhagen School Health Records Register, born 1930 to 1987 with information on measured weights and heights at ages 6 to 15 years. Five sex-specific childhood BMI trajectories were analyzed. Information on the main outcomes CKD and ESKD, as well as T2D, came from national health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using Poisson regression adjusted for year of birth. During a median of 30.8 person-years of follow-up, 5,968 men and 3,903 women developed CKD and 977 men and 543 women developed ESKD. For both sexes, the rates of CKD and ESKD increased significantly with higher child BMI trajectories in comparison with the average BMI trajectory (40% to 43% of individuals) and the below-average BMI trajectory (21% to 23% of individuals) had the lowest rates. When including T2D, most associations were significant and men (IRR = 1.39, 95% CI: 1.13 to 1.72) and women (IRR = 1.54, 95% CI: 1.28 to 1.86) with the obese childhood BMI trajectory (2% of individuals) had significantly higher CKD rates than the average BMI trajectory, whereas for ESKD, the associations were positive, but nonsignificant, for men (IRR = 1.38, 95% CI: 0.83 to 2.31) but significant for women (IRR = 1.97, 95% CI: 1.25 to 3.11) with the obese BMI trajectory. A main study limitation is the use of only hospital-based CKD diagnoses. CONCLUSIONS: Individuals with childhood BMI trajectories above average had higher rates of CKD and ESKD than those with an average childhood BMI trajectory. When including T2D, most associations were significant, particularly with CKD, emphasizing the potential information that the early appearance of above-average BMI growth patterns provide in relation to adult-onset CKD beyond the information provided by T2D development.

Early life body size, pubertal timing, and risks of benign breast disease in a large cohort of Danish female adolescents and women.

A high childhood body mass index (BMI) may be protective against benign breast disease (BBD), but little is known about the effects of other early life body size measures. Thus, we examined associations between birthweight, childhood BMI, height, and pubertal timing and BBD risks. We included 171,272 girls, born from 1930 to 1996, from the Copenhagen School Health Records Register, which contains information on birthweight, childhood anthropometry (7-13 years), age at onset of the growth spurt (OGS), and peak height velocity (PHV). During follow-up, 9361 BBD cases (15-50 years) were registered in the Danish National Patient Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. At all childhood ages, BMI was inversely but non-linearly associated with BBD. The association was slightly stronger in magnitude for BMI z-scores above 0 (HRage 7 = 0.86; 95%CI: 0.83-0.90 per z-score) than below 0 (HRage 7 = 0.95; 95%CI 0.91-0.99 per z-score). Associations between childhood height and BBD differed by age; at 7 years the association was an inverted U-shape, whereas at 13 years height was not associated with BBD. Ages at OGS and PHV were positively associated with BBD. Low and high birthweights were associated with lower BBD risks.   Conclusion: A high childhood BMI, a short or tall stature at young childhood ages, an early pubertal onset, and low or high birthweights are associated with reduced risks of BBD. These complex associations suggest that the role of these factors in breast tissue development during early life warrants further investigation in relation to BBD etiology. What is Known: • Benign breast disease (BBD) is common and may be an intermediary marker of breast cancer risks. • Early life body size may relate to the development of BBD, but currently little is known. What is New: • Girls with a high body mass index at school ages or with an early pubertal timing have decreased risks of BBD. • Short and tall heights at young childhood ages and low and high birthweights are associated with lower BBD risks.

Birthweight, childhood overweight, height and growth and adult cancer risks: a review of studies using the Copenhagen School Health Records Register.

BACKGROUND: Most identified risk factors for cancer primarily occur in adulthood. As cancers generally have long latency periods, it is possible that risk factors acting earlier in life and accumulation of risks across the life course are important. Thus, focusing only on adult overweight as a modifiable risk factor may overlook childhood as an important aetiologic time window when body size is relevant for future cancer risks. The objective of this study was to review the evidence for associations between birthweight, body mass index (BMI), height and growth from 7-13 years and adult cancer risks based on studies using the Copenhagen School Health Records Register. METHODS: The register contains measured anthropometric information on 372,636 children born in 1930-1989. All studies examining associations between early life body size and risks of adult cancer (until 85 years, diagnosed in 1968-2015) were included, comprising 31 studies on 16 different cancer sites. Cancer diagnoses were retrieved via individual-level linkages to the Danish Cancer Registry. RESULTS: Birthweight was differentially associated with bladder, breast, colon, glioma, Hodgkin's disease, liver, kidney (renal cell), melanoma, ovarian, rectal, testicular and thyroid cancer. BMI in childhood was positively associated with risks of bladder (only late childhood), colon, endometrial, kidney, liver, oesophageal (only late childhood), ovarian, pancreatic (<70 years), prostate (only before childhood height adjustment) and thyroid cancer, whereas it was inversely associated with breast cancer. Child height was positively associated with breast, colon, endometrial, glioma, Hodgkin's disease, kidney, melanoma, oesophageal (only women), ovarian, prostate, testicular and thyroid cancer and inversely associated with bladder cancer. Greater than average increases in childhood BMI or linear growth at ages 7-13 increased risks of several cancers. CONCLUSIONS: Early life body size and growth are associated with many, but not all adult cancers, suggesting that the aetiology of several cancers may lie earlier in life than previously thought.

Changes and correlations in height from 7 to 69 years of age across the birth years of 1930 to 1989.

OBJECTIVES: The aims of this study were to describe changes in height during childhood and to investigate potential changes in the proportion of children attaining final height in childhood and in correlations between child and adult height across birth cohorts. METHODS: We included 363 059 children (179 906 girls) from the Copenhagen School Health Records Register, who were born between 1930 and 1989, with height measurements at ages 7, 10, or 13 years. Linkages to data resources containing adult height values between ages 18 and 69 years were possible for a subpopulation of 96 133 individuals (23 051 women). Birth years were categorized as 1930 to 1939, 1940 to 1949, and 1950 to 1989. Descriptive height statistics were estimated by birth years and birth cohorts. Height correlations were examined using sex- and age-specific partial Pearson correlation analyses and meta-regression techniques. RESULTS: Across 60 birth years, mean child heights at age 7 increased by 2.9 cm in girls and 3.0 cm in boys, and adult heights increased as well. The proportions of children attaining final height by age 13 remained low across the birth cohorts; nonetheless, there was a significant increase from 0.7% to 1.5% in girls only (P < .0001). Both child-child and child-adult height correlations were strong and remained relatively stable across birth cohorts. CONCLUSIONS: Mean child and adult height increased during the study period, but the proportion of children attaining final height at age 13 remained low. Child-child and child-adult height correlations were largely unchanged across birth cohorts.

Birth weight, childhood body mass index and height and risks of endometriosis and adenomyosis.

Background: Body size in adult life is likely associated with risks of endometriosis and adenomyosis, yet little is known about associations with body size earlier in life.Aim: To examine whether birth weight, childhood body mass index (BMI) and height are associated with risks of endometriosis and adenomyosis.Subjects and methods: From the Copenhagen School Health Records Register, 171,447 girls born 1930-1996, with measured weights and heights at ages 7-13 were included. Outcomes were obtained from health registers. Cox regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI).Results: During follow-up, 2149 endometriosis cases and 1410 adenomyosis cases were diagnosed. Childhood BMI was inversely associated with endometriosis (HR = 0.92 [95% CI: 0.88-0.96] per z-score at age 7). In contrast, childhood height was positively associated with endometriosis (HR = 1.09 [95% CI: 1.05-1.14] per z-score at age 7). Associations with childhood body size did not differ by endometriosis location. Childhood BMI and height had limited associations with adenomyosis. Birth weight was not associated with endometriosis or adenomyosis.Conclusion: Lean and tall girls are more often diagnosed with endometriosis, but not adenomyosis. These findings suggest that indicators of endometriosis risk are already apparent at early ages.

Early life body size and its associations with adult bladder cancer.

Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.Aim: To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC.Subjects and methods: Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.Results: 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively.Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.

Childhood height and risk of testicular germ cell tumors in adulthood.

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.

Birth weight and the risk of histological subtypes of ovarian and endometrial cancers: Results from the Copenhagen School Health Records Register.

BACKGROUND: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ovarian and endometrial cancers overall and by histologic subtype. METHODS: 162,559 girls, born from 1930 to 1989, from the Copenhagen School Health Records Register (CSHRR) were followed prospectively via linkage with the Danish health registers. Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to 2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A decreased risk of Type II endometrial tumors was suggested per kilogram increase in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS: Our results suggest that both lower and higher birth weights were associated with increased ovarian cancer risk and associations were particularly strong for serous ovarian cancer, the most common subtype. Birth weight was not associated with most types of endometrial cancer.

Childhood body mass index growth trajectories and endometrial cancer risk.

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

Childhood height, adult height, and the risk of prostate cancer.

PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk. When adjusted for adult height, height at age 7 years was no longer significantly associated with the risk of prostate cancer. Height at 13 years was significantly and positively associated with prostate cancer risk even when adult height was adjusted for; per height z-score the hazard ratio was 1.15 [95% confidence interval (CI) 1.01-1.32]. CONCLUSIONS: The effect of height at 13 years on the risk of prostate cancer was not entirely mediated through adult height, suggesting that child height and adult height may be associated with prostate cancer through different pathways.

Early life body size and puberty markers as predictors of breast cancer risk later in life: A neural network analysis.

BACKGROUND: The early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer. METHODS: We used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model. RESULTS: The highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076. CONCLUSION: We found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models.

Plasma enterolactone and incidence of endometrial cancer in a case-cohort study of Danish women.

The phyto-oestrogen enterolactone has been hypothesised to protect against hormone-dependent cancers, probably through its antioestrogenic potential. We investigated whether a higher level of plasma enterolactone was associated with a lower incidence of endometrial cancer in a case-cohort study in the 'Diet, Cancer and Health' cohort. The cohort study included 29 875 women aged 50­64 years enrolled between 1993 and 1997. Information on diet and lifestyle was provided by self-administrated questionnaires and blood was drawn from each participant. Time-resolved fluoroimmunoassay was used for biochemical determination of plasma enterolactone. A total of 173 cases and 149 randomly selected cohort members were included. We estimated incidence rate ratio (IRR) and 95% CI by a Cox proportional hazards model. A 20 nmol/l higher plasma concentration of enterolactone was associated with a non-significant lower risk of endometrial cancer (IRR 0.93, 95% CI 0.84, 1.04). When excluding women with low enterolactone concentrations (quartile 1) due to potential recent antibiotic use, the association became slightly stronger, but remained non-significant (IRR 0.90, 95% CI 0.79, 1.02). Menopausal status, hormone replacement therapy or BMI did not modify the association. In conclusion, we found some support for a possible inverse association between plasma enterolactone concentration and endometrial cancer incidence.

Childhood body mass index trajectories, adult-onset type 2 diabetes, and obesity-related cancers.

BACKGROUND: Elevated childhood body mass index (BMI), commonly examined as a "once-only" value, increases the risk of cancer and type 2 diabetes (T2D) in adulthood. Continuous exposure to adiposity during childhood may further increase cancer risk. We examined whether longitudinal childhood BMI trajectories were associated with adult obesity-related cancer and the role of adult-onset T2D in these associations. METHODS: Five sex-specific latent class BMI trajectories were generated for 301 927 children (149 325 girls) aged 6-15 years from the Copenhagen School Health Records Register. Information on obesity-related cancers and T2D was obtained from national health registers. Incidence rate ratios (IRR), cumulative incidences, and confidence intervals (CI) were estimated using Poisson regressions. RESULTS: Compared with the average childhood BMI trajectory (containing approximately 40% of individuals), the rate of obesity-related cancer (excluding breast cancer) increased with higher childhood BMI trajectories among women. The highest rates occurred in the overweight (IRR = 1.27, 95% CI = 1.17 to 1.38) and obesity (IRR = 1.79, 95% CI = 1.53 to 2.08) BMI trajectories. Similar patterns were observed among men. In contrast, women with the obesity childhood BMI trajectory had the lowest rate of pre- and postmenopausal breast cancer (IRR = 0.59, 95% CI = 0.43 to 0.80, and IRR = 0.41, 95% CI = 0.30 to 0.57, respectively). For all trajectories, the cumulative risk of obesity-related cancer increased with adult-onset T2D. CONCLUSION: Consistent childhood overweight or obesity may increase the rates of adult obesity-related cancer and decrease the rates of breast cancer. Adult-onset T2D conferred additional risk for obesity-related cancer, but the effect did not differ across childhood BMI trajectories.

Trajectories of body mass index across the lifecourse and associations with post-menopausal breast cancer by estrogen receptor status.

BACKGROUND: Associations between a high body mass index (BMI) at single timepoints during child- and adulthood and risks of post-menopausal breast cancer are well-established, but associations with BMI across the lifecourse remains largely unknown. Therefore, we examined whether lifecourse BMI trajectories were associated with risks of post-menopausal breast cancer overall and by estrogen receptor (ER) status. METHODS: We included 6698 Danish women born 1930-1946. Information on BMI at ages 6-15 years came from the Copenhagen School Health Records Register, and information on BMI at ages 20, 30, 40, 50 and/or 50-64 years came from the Diet, Cancer and Health cohort. Breast cancer cases (n = 577) were identified in the Danish Breast Cancer Cooperative Group database. Six BMI trajectories were identified using latent class trajectory modelling. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models. RESULTS: Compared to women with a trajectory characterized by an average BMI gain across life, women with the two trajectories with steep increases in BMI during childhood and adolescence that thereafter largely stabilized, had lower risks of post-menopausal breast cancer and ER-positive tumors. The adjusted HRs for ER-positive tumors were 0.67 (95% CI: 0.47-0.95) and 0.68 (95% CI: 0.46-1.01), respectively. In contrast, women with a trajectory with a low gain in BMI during childhood and adolescence followed by a subsequent steep increase during adulthood, had higher risks of post-menopausal breast cancer and ER-positive tumors when compared to women with an average BMI gain. The adjusted HR for ER-positive tumors was 1.28 (95% CI: 0.98-1.67). CONCLUSIONS: Our findings suggest that the timing of excess gain in BMI across the lifecourse impacts subsequent post-menopausal breast cancer risks. Thus, the BMI development across life is likely useful in the identification of women at increased risks of post-menopausal breast cancer.

Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy.

OBJECTIVE: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. METHODS: A nested case-control study was conducted within the prospective Danish population-based 'Diet, Cancer, and Health' cohort. During follow-up, 348 eligible cases were identified among 20,861 postmenopausal women and matched to 348 controls. Baseline serum samples were analyzed for estradiol, bioavailable estradiol, estrone, estrone sulfate, and SHBG. Conditional logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders. RESULTS: Modest direct associations were identified between estrogen levels and breast cancer incidence among both never and baseline HRT users. Estrone and estrone sulfate were more consistently associated among both groups than estradiol. No association was found with SHBG. CONCLUSION: Despite different hormonal profiles, higher serum estrogen levels were associated with a higher risk of breast cancer among both never and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.

Whole grain, dietary fiber, and incidence of endometrial cancer in a Danish cohort study.

Whole grains and dietary fiber might be inversely associated with endometrial cancer risk through their effects on sex hormone metabolism and body fat. We investigated whether a higher intake of whole grains and dietary fiber was associated with a lower incidence of endometrial cancer in the Diet, Cancer and Health cohort of 29,875 women aged 50-64 years at enrollment in 1993-1997. Information on diet and lifestyle was derived from self-administered questionnaires. The incidence rate ratios and 95% confidence intervals were estimated based on a Cox proportional hazards model. Of the 24,418 women included as cohort members, 217 had a diagnosis of endometrial cancer. No clear associations were found between intake of whole grains or dietary fiber and the incidence of endometrial cancer.

Body mass index trajectories in childhood and incidence rates of type 2 diabetes and coronary heart disease in adulthood: A cohort study.

AIMS: We examined associations between five body mass index (BMI) trajectories from ages 6-15 years and register-based adult-onset type 2 diabetes mellitus (T2D) and coronary heart disease (CHD) with and without adjustment for adult BMI. METHODS: Child and adult BMI came from two Danish cohorts and 13,205 and 13,438 individuals were included in T2D and CHD analyses, respectively. Trajectories were estimated by latent class modelling. Incidence rate ratios (IRRs) were estimated with Poisson regression. RESULTS: In models without adult BMI, compared to the lowest trajectory, among men the T2D IRRs were 0.92 (95 %CI:0.77-1.09) for the second lowest trajectory and 1.51 (95 %CI:0.71-3.20) for the highest trajectory. The corresponding IRRs in women were 0.92 (95 %CI:0.74-1.16) and 3.58 (95 %CI:2.30-5.57). In models including adult BMI, compared to the lowest trajectory, T2D IRRs in men were 0.57 (95 %CI:0.47-0.68) for the second lowest trajectory and 0.26 (95 %CI:0.12-0.56) for the highest trajectory. The corresponding IRRs in women were 0.60 (95 %CI:0.48-0.75) and 0.59 (95 %CI:0.36-0.96). The associations were similar in direction, but not statistically significant, for CHD. CONCLUSIONS: Incidence rates of adult-onset T2D were greater for a high child BMI trajectory than a low child BMI trajectory, but not in models that included adult BMI.

Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome.

INTRODUCTION: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown. OBJECTIVE: To investigate associations between a woman's own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS. METHODS: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960-1996, with information on birthweight and measured weight and height at the ages of 7-13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15-50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis. RESULTS: Birthweight was not associated with PCOS. At the age of 7-13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34-3.42) at age 7 years and 2.99 (95% CI 2.38-3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth. CONCLUSION: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark.

Importance: Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective: To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants: This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures: Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures: Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results: This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. Conclusions and Relevance: This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.