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.

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.

Birth weight, childhood body mass index, and risk of diverticular disease in adulthood.

OBJECTIVE: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. METHODS: Cohort study of 346,586 persons born during 1930-1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18-49 and from age 50. RESULTS: During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98-1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11-1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85-1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34-1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83-0.99) per 500 g higher birthweight]. CONCLUSION: BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight.

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.

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.

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.

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.

Trajectories of Infant Weight Gain from Birth to 12 Months and Adult-Onset Coronary Heart Disease.

OBJECTIVE: To investigate associations between infant weight gain trajectories and coronary heart disease (CHD). STUDY DESIGN: We followed 3645 Danish individuals born between 1959 and 1961 with information on weight at birth and at age 2 weeks and 1, 2, 3, 4, 6, or 12 months. Sex-specific weight trajectories were generated using latent class modeling. Cases of CHD (n = 279) were identified from national health registers. Hazard ratios (HRs) were estimated by Cox regression with sequential adjustment for sex, socioeconomic status, prepregnancy body mass index, maternal smoking, preterm birth, parity, and birth weight. RESULTS: We identified 5 trajectories of weight development in infancy in our cohort: very low-moderate increase (11.5% of the population), low-marked increase (13.9%), low-stable increase (32.4%), average-stable increase (29.8%), and high-moderate increase (12.4%). Compared with the average-stable increasing trajectory, having a very low-moderately increasing weight trajectory in infancy was associated with a higher frequency of adult CHD (HR, 1.56; 95% CI, 1.04-2.33). The higher frequency remained after adjustment for maternal factors but was slightly attenuated after additional adjustment for preterm birth and parity (HR, 1.41; 95% CI, 0.91-2.23) and disappeared after adjustment for birth weight (HR, 0.78; 95% CI, 0.44-1.37). The associations with CHD did not differ between the other trajectories and the average-stable increasing trajectory. CONCLUSIONS: Although a pattern of very low-moderate increasing weight during infancy was associated with a higher frequency of adult CHD, the association did not persist after adjustment for birth weight, highlighting the importance of prenatal exposures.

Weight Changes in Type 2 Diabetes and Cancer Risk: A Latent Class Trajectory Model Study.

INTRODUCTION: Body mass index (BMI) is often elevated at type 2 diabetes (T2D) diagnosis. Using latent class trajectory modelling (LCTM) of BMI, we examined whether weight loss after diagnosis influenced cancer incidence and all-cause mortality. METHODS: From 1995 to 2010, we identified 7,708 patients with T2D from the Salford Integrated Record database (UK) and linked to the cancer registry for information on obesity-related cancer (ORC), non-ORC; and all-cause mortality. Repeated BMIs were used to construct sex-specific latent class trajectories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS: Four sex-specific BMI classes were identified; stable-overweight, stable-obese, obese-slightly-decreasing, and obese-steeply-decreasing; comprising 41%, 45%, 13%, and 1% of women, and 45%, 37%, 17%, and 1% of men, respectively. In women, the stable-obese class had similar ORC risks as the obese-slightly-decreasing class, whereas the stable-overweight class had lower risks. In men, the obese-slightly-decreasing class had higher risks of ORC (HR = 1.86, 95% CI: 1.05-3.32) than the stable-obese class, while the stable-overweight class had similar risks No associations were observed for non-ORC. Compared to the stable-obese class, women (HR = 1.60, 95% CI: 0.99-2.58) and men (HR = 2.37, 95% CI: 1.66-3.39) in the obese-slightly-decreasing class had elevated mortality. No associations were observed for the stable-overweight classes. CONCLUSION: Patients who lost weight after T2D diagnosis had higher risks for ORC (in men) and higher all-cause mortality (both genders) than patients with stable obesity.

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.

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, growth and risks of systemic lupus erythematosus - A large Danish observational cohort study.

OBJECTIVES: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that size earlier in life may be important in the aetiology of SLE as well. We investigated whether birthweight, childhood body mass index (BMI; [kg/m2]), height and growth are associated with risks of adult SLE. METHODS: The study included 346,627 children from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights from 7-13 years. Birthweight information was available from 1936. Linkages were made to the Danish National Patient Register for information on registrations of SLE. During follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazards regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: No differences by sex were detected in any of the associations. Birthweight was not associated with SLE risks. Childhood BMI and height were positively and linearly associated with SLE risks. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. The estimates were similar in magnitude across all childhood ages for BMI and height. There were limited indications that change in BMI or growth in height during childhood influence the risks of SLE in adulthood. CONCLUSIONS: Childhood body size is associated with risks of adult SLE, which supports the hypothesis that early life factors are important in SLE aetiology.

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.

Inflammatory Bowel Diseases Increase Risk of Type 2 Diabetes in a Nationwide Cohort Study.

BACKGROUND & AIMS: The intestine regulates glucose homeostasis, but it is not clear whether chronic intestinal inflammation affects risk for type 2 diabetes. We investigated the long-term risk of type 2 diabetes in patients with inflammatory bowel diseases (IBD) in a nationwide cohort study in Denmark. METHODS: In a nationwide population-based cohort of 6,028,844 persons in Denmark, we compared data from individuals with a diagnosis of IBD (Crohn's disease [CD] or ulcerative colitis UC]) with data from individuals from the general population from 1977 through 2014. Persons with type 2 diabetes were identified in the National Patient Register. Risk is presented as standardized incidence ratios (SIR) with 95% CIs. RESULTS: During 736,072 person-years of follow-up, 3436 patients with IBD developed type 2 diabetes vs 2224 expected (SIR, 1.54; 95% CI, 1.49-1.60). The risk was significantly increased in patients with UC (SIR, 1.54; 95% CI, 1.48-1.60), in patients with CD (SIR, 1.57; 95% CI, 1.47-1.67), in women (SIR, 1.51; 95% CI, 1.44-1.59), and in men (SIR, 1.57; 95% CI, 1.50-1.65). The risk was highest the first year after a diagnosis of IBD (SIR, 4.48; 95% CI, 4.16-4.83), but remained increased for 20 or more years following the diagnosis (SIR, 1.26; 95% CI, 1.16-1.38). The increased risk could not be accounted for by frequency of health care contacts or corticosteroid exposure. Patients who received a diagnosis of IBD from 2003 through 2014 (SIR, 1.79; 95% CI, 1.67-1.91) had a significantly higher risk of type 2 diabetes than patients who received a diagnosis of IBD from 1977 through 1988 (SIR, 1.47; 95% CI, 1.39-1.56) or 1989 through 2002 (SIR, 1.48; 95% CI, 1.41-1.56) (P < .001). CONCLUSIONS: In a population-based cohort study, we found an increased risk of type 2 diabetes in patients with UC or CD, with highest risk estimates from 2003 through 2014, compared with earlier years. Studies are needed to determine the effects of IBD treatment on risk of type 2 diabetes.

Overweight Patterns Between Childhood and Early Adulthood and Esophageal and Gastric Cardia Adenocarcinoma Risk.

OBJECTIVE: Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear. METHODS: This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7-13 years) and early adulthood (17-26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. RESULTS: The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50-4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57-6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood. CONCLUSIONS: Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.

Change in weight status from childhood to early adulthood and late adulthood risk of colon cancer in men: a population-based cohort study.

BACKGROUND: Although weight gain in mid- to late adult life is associated with an increased risk of colon cancer, it is unclear if increases or losses in weight from childhood to early adulthood are differentially associated with risks of adult colon cancer. METHODS: Weight and height were measured at 7 or 13 years and in early adulthood (17-26 years) in 64,675 boys in the Copenhagen School Health Records Register and the Danish Conscription Database. Cases of colon cancer (n = 751) were identified in the Danish Cancer Registry. Boys and young men were categorized as normal weight or overweight. Associations between changes in weight and colon cancer were examined using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with men with a normal weight at 7 years and in early adulthood, men with overweight at both ages had an increased risk of adult colon cancer (HR: 2.73, 95% CI 1.80-4.15). In contrast, men with overweight at 7 years, but not in early adulthood did not have an increased risk of colon cancer (HR: 0.73, 95% CI 0.35-1.54), nor did men with a normal weight at 7 years and overweight in early adulthood (HR: 1.28, 95% CI 0.96-1.70). Similar results were observed for weight status at age 13 years combined with early adulthood. CONCLUSIONS: Childhood overweight that persists into early adulthood is associated with an increased risk of colon cancer, whereas overweight that disappears before early adulthood or developed after childhood is not.

Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes.

BACKGROUND: Childhood overweight is associated with an increased risk of type 2 diabetes in adulthood. We investigated whether remission of overweight before early adulthood reduces this risk. METHODS: We conducted a study involving 62,565 Danish men whose weights and heights had been measured at 7 and 13 years of age and in early adulthood (17 to 26 years of age). Overweight was defined in accordance with Centers for Disease Control and Prevention criteria. Data on type 2 diabetes status (at age ≥30 years, 6710 persons) were obtained from a national health registry. RESULTS: Overweight at 7 years of age (3373 of 62,565 men; 5.4%), 13 years of age (3418 of 62,565; 5.5%), or early adulthood (5108 of 62,565; 8.2%) was positively associated with the risk of type 2 diabetes; associations were stronger at older ages at overweight and at younger ages at diagnosis of type 2 diabetes. Men who had had remission of overweight before the age of 13 years had a risk of having type 2 diabetes diagnosed at 30 to 60 years of age that was similar to that among men who had never been overweight (hazard ratio, 0.96; 95% confidence interval [CI], 0.75 to 1.21). As compared with men who had never been overweight, men who had been overweight at 7 and 13 years of age but not during early adulthood had a higher risk of type 2 diabetes (hazard ratio, 1.47; 95% CI, 1.10 to 1.98), but their risk was lower than that among men with persistent overweight (hazard ratio [persistently overweight vs. never overweight], 4.14; 95% CI, 3.57 to 4.79). An increase in body-mass index between 7 years of age and early adulthood was associated with an increased risk of type 2 diabetes, even among men whose weight had been normal at 7 years of age. CONCLUSIONS: Childhood overweight at 7 years of age was associated with increased risks of adult type 2 diabetes only if it continued until puberty or later ages. (Funded by the European Union.).

Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life.

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m2) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04-1.14) and 1.14 (95% CI 1.09-1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.

Height at Ages 7-13 Years in Relation to Developing Type 2 Diabetes Throughout Adult Life.

BACKGROUND: Short adults have an increased risk of type 2 diabetes. Although adult height results from childhood growth, the effects of height and growth trajectories during childhood are sparsely investigated. We investigated sex-specific associations between childhood height, growth and adult type 2 diabetes, including potential influences of birthweight and childhood body mass index (BMI). METHODS: We followed 292 827 individuals, born 1930-83, from the Copenhagen School Health Records Register in national registers for type 2 diabetes (11 548 men; 7472 women). Weights and heights were measured at ages 7-13 years. Hazard ratios (HR) of type 2 diabetes (age ≥30 years) were estimated without and with adjustment for birthweight and BMI. RESULTS: In men, associations between height and type 2 diabetes changed from inverse for below-average heights at age 7 years to positive for above-average heights at 13 years. No consistent associations were observed among women. These associations were not affected by birthweight. After adjustment for BMI, below-average childhood heights were inversely associated with type 2 diabetes among men (HR range: 0.91-0.93 per z-score) but above-average heights were not. Among women, after adjustment for BMI, below- and above-average heights in childhood were inversely associated with type 2 diabetes (HR range: 0.91-0.95). Greater height growth from 7 to 13 years was positively associated with type 2 diabetes in men and women. CONCLUSIONS: After adjustment for BMI, short childhood height at all ages and greater growth during childhood are associated with an increased risk of type 2 diabetes, suggesting that this period of life warrants mechanistic investigations.