TienYu Owen Yang

Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies

BACKGROUND Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. METHODS Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. FINDINGS The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. INTERPRETATION Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). FUNDING Medical Research Council, Cancer Research UK.

Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study.

Background:Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear.Methods:Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression.Results:Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m−2 increase in BMI, 95% confidence interval (CI): 1.77–1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09–1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77–1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61–2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88–1.22).Conclusion:Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women’s current BMI.

Parent Support, Peer Support, and Peer Acceptance in Healthy Lifestyle for Asthma Management Among Early Adolescents

PURPOSE This study aims to investigate the association between social support variables and healthy lifestyle for asthma management among early adolescents (ages 9-14 years). DESIGN AND METHODS Questionnaires were completed by 86 parent-adolescent dyads. RESULTS Healthy lifestyle was associated with social support variables. The association with peer acceptance was stronger among adolescents who received less asthma-specific support from peers. Age was negatively associated with healthy lifestyle, but the association was attenuated after adjustment for asthma-specific peer support. PRACTICE IMPLICATIONS The findings of this study suggest recognizing the developmental change of social support during early adolescence.

Birth weight and adult cancer incidence: large prospective study and meta-analysis

BACKGROUND Most evidence about associations between birth weight and adult cancer risk comes from studies linking birth records to cancer registration data, where information on known risk factors for cancer is generally lacking. Here, we report on associations between birth weight and cause-specific cancer risk in a large cohort of UK women, and investigate how observed associations are affected by other factors. METHODS A total of 453 023 women, born in the 1930s and 1940s, reported their birth weight, maternal smoking, parental heights, age at menarche, adult height, adult smoking, and many other personal characteristics. They were followed for incident cancer. Using Cox regression, relative risks by birth weight were estimated for cancers with more than 1500 incident cases, adjusting for 17 potential confounding factors, individually and simultaneously. RESULTS Birth weight reported in adulthood was strongly correlated with that recorded at birth (correlation coefficient = 0.78, P < 0.0001). Reported birth weight was associated with most of the potential confounding factors examined, the strongest association being with adult height. After 9.2 years follow-up per woman, 39 060 incident cancers were registered (4414 colorectal, 3175 lung, 1795 malignant melanoma, 14 542 breast, 2623 endometrial, 2009 ovarian, 1565 non-Hodgkin lymphoma, and 8937 other cancers). Associations with birth weight were null or weak and reduced after adjustment by adult height (P[trend] > 0.01 for every cancer, after adjustment). In contrast, adult height was strongly related to the risk of every cancer except lung cancer, after adjusting for birth weight and other factors (P[trend] < 0.0001 for most cancers). For lung cancer, adjusting for smoking reduced the association with birth weight. Meta-analyses were dominated by our findings. CONCLUSION Birth weight and adult height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women.Birth weight and height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women.

Tea and coffee and risk of endometrial cancer: cohort study and meta-analysis

Background: Previous reports, mostly from retrospective studies, suggested possible protective effects of both tea and coffee against endometrial cancer, but recent reports from prospective studies generally showed weaker or null associations. Objectives: We investigated endometrial cancer risk in relation to tea and coffee consumption in a large prospective study and did a meta-analysis of published results. Design: Daily consumption of tea and coffee was recorded in 560,356 participants (without a hysterectomy) in the UK Million Women Study of whom 4067 women developed endometrial cancer during 5.2 million person-years of follow up (average: 9.3 y per woman). Results: With the use of Cox proportional hazards regression, we showed no significant association between endometrial cancer risk and consumption of either tea (multivariate adjusted RR per cup daily: 1.00; 95% CI: 0.98, 1.02) or coffee (RR per cup daily: 0.98; 95% CI: 0.96, 1.01). Our meta-analyses showed no significant association between endometrial cancer risk and tea consumption and a weak association for coffee consumption in prospective studies, but there may have been selective publication of only part of the evidence. Conclusions: There is little or no association between tea consumption and endometrial cancer risk. If there is any association with coffee consumption, it appears to be weak.

Adiposity and ischemic and hemorrhagic stroke: Prospective study in women and meta-analysis

Objective: To compare associations of body mass index (BMI) with ischemic stroke and hemorrhagic stroke risk, and to review the worldwide evidence. Methods: We recruited 1.3 million previously stroke-free UK women between 1996 and 2001 (mean age 57 years [SD 5]) and followed them by record linkage for hospital admissions and deaths. We used Cox regression to estimate adjusted relative risks for ischemic and hemorrhagic (intracerebral or subarachnoid hemorrhage) stroke in relation to BMI. We conducted a meta-analysis of published findings from prospective studies on these associations. Results: During an average follow-up of 11.7 years, there were 20,549 first strokes, of which 9,993 were specified as ischemic and 5,852 as hemorrhagic. Increased BMI was associated with an increased risk of ischemic stroke (relative risk 1.21 per 5 kg/m2 BMI, 95% confidence interval 1.18–1.23, p < 0.0001) but a decreased risk of hemorrhagic stroke (relative risk 0.89 per 5 kg/m2 BMI, 0.86–0.92, p < 0.0001). The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different (heterogeneity: p < 0.0001) but were not significantly different for intracerebral hemorrhage (n = 2,790) and subarachnoid hemorrhage (n = 3,062) (heterogeneity: p = 0.5). Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic than hemorrhagic stroke with most evidence (prior to this study) coming from Asian populations. Conclusions: In UK women, higher BMI is associated with increased risk of ischemic stroke but decreased risk of hemorrhagic stroke. The totality of the available published evidence suggests that BMI-associated risks are greater for ischemic than for hemorrhagic stroke.

Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood.

Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17‐1.51, for BMI 35+ vs <22.5 kg/m2), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10–1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.

Differences in risk factors for 3 types of stroke: UK prospective study and meta-analyses.

Objective To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. Methods A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999–2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies. Results After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84–2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04–1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26–0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30–1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12–5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94–2.72] or ischemic stroke [RR 2.50, 95% CI 2.29–2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke. Conclusion Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

Specific and Non-specific Clinical Presentations in the Year Before the Diagnosis of Childhood Leukaemia.

Clinical presentations of childhood leukaemia have been reported in case‐only studies. The timing when these presentations start to occur prior to diagnosis is less clear.

Diagnostic uncertainty of herpangina and hand-foot-and-mouth disease and its impact on national enterovirus syndromic monitoring.

The community burden of enterovirus is often monitored through syndromic monitoring systems based on reported cases of enterovirus-related infection (EVI) diagnoses. The extent to which this is affected by under- and over-diagnosis has not been reported. In Taiwan, children often make more than one healthcare visit during an episode of infection. We used change of diagnosis within an episode of infection as a guide of diagnostic uncertainty in a nationally representative cohort of Taiwanese children (n = 13 284) followed from birth to the 9th birthday through electronic health records. We conducted a nested case-control analysis and estimated cross-diagnosis ratios (CDRs) as the observed proportion of acute respiratory infection (ARI) diagnoses following an EVI diagnosis in excess of background ARI burdens. With 19 357 EVI diagnoses in this cohort, the CDR within 7 days was 1·51 (95% confidence interval 1·45-1·57), confirming a significant excess of ARI diagnoses within the week following an EVI diagnosis. We used age-specific CDRs to calibrate the weekly EVI burden in children aged 3-5 years in 2008, and the difference between observed and calibrated weekly EVI burdens was small. Therefore, there was evidence suggesting a small uncertainty in EVI diagnosis, but the observed EVI burdens through syndromic monitoring were not substantially affected by the small uncertainty.