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1.
Int J Cancer ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584193

RESUMO

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four time points over 25-years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n=70,397) aged 50-79 years without breast cancer at enrollment (1993-1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared with women with birth weight of 6 to 8 pounds, women with birth weight of less than 6 pounds had lower risk of breast cancer (HR=0.88 95% CI: 0.79-0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer. This article is protected by copyright. All rights reserved.

2.
Cancer Causes Control ; 30(11): 1201-1211, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542834

RESUMO

PURPOSE: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users. METHODS: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. RESULTS: Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT). CONCLUSIONS: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.

3.
Obstet Gynecol ; 134(3): 591-599, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403595

RESUMO

OBJECTIVE: To examine associations among parity, breastfeeding history, and risk of developing type 2 diabetes among postmenopausal women. METHODS: A prospective cohort study was conducted. One hundred thirty-six thousand six hundred fifty-two postmenopausal women aged 50-79 years participating in the Women's Health Initiative recruited from 40 clinical centers throughout the United States between 1993 and 1998, without baseline cancer or diabetes were followed for 14.2 years. Parity and breastfeeding data were collected by questionnaires administrated to all participants at baseline. Incident diabetes was assessed via validated self-report of physician-diagnosed diabetes treated with insulin or other hypoglycemic medications. Multivariable Cox proportional hazards regression models were used to assess associations between parity, breastfeeding and diabetes incidence, and racial-ethnic differences in the associations. RESULTS: During follow-up, 18,812 cases of incident diabetes were identified. Overall, a greater number of term pregnancies was associated with increased risk of diabetes (P for trend=.002), and longer duration of breastfeeding was associated with lower risk of diabetes (P for trend <.01). After further adjusting for adult weight gain among a subset of the cohort (n=75,558) with 9,110 cases, the association between parity and risk of diabetes were attenuated and became nonsignificant. Also, parous women with fewer than five term pregnancies did not have increased diabetes risk when breastfeeding for 3 months or more per child, which was associated with less weight gain. CONCLUSION: The results of this large, prospective study showed that the association between parity and risk of type 2 diabetes was most likely confounded by adult weight gain among postmenopausal women.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31448952

RESUMO

Background: Home-based video visits were provided over one year as a supplement to in-person care for pediatric type 1 diabetes (T1D) patients with suboptimal glycemic control. We hypothesized that the intervention would be feasible and satisfactory for the target population and would significantly improve hemoglobin A1c (HbA1c) levels and completion of recommended quarterly diabetes clinic visits. Methods: This was a nonrandomized clinical trial. Fifty-seven patients aged 3-17 years with known T1D and HbA1c ≥8% (64 mmol/mol) were recruited to receive the intervention. The study population was 49% adolescent (13-17 years old) and 58% publicly insured patients. Video visits were scheduled every 4, 6, or 8 weeks depending on the HbA1c level. HbA1c levels as well as frequencies of clinic visits and of diabetes-related emergency department (ED) and hospital encounters were compared before and after the study. Results: Thirty participants completed 12 months of video visits. The study cohort demonstrated significant improvement in mean HbA1c in both intention-to-treat (N = 57) analysis (10.8% [95 mmol/mol] to 10.0% [86 mmol/mol], P = 0.01) and per-protocol (N = 30) analysis (10.8% [95 mmol/mol] to 9.6% [81 mmol/mol], P = 0.004). Completion of ≥4 annual diabetes clinic visits improved significantly from 21% at baseline to 83% during the study period for the entire cohort, P < 0.0001. The frequency of diabetes-related ED and hospital encounters did not change significantly. Conclusions: Home-based video visits are a feasible supplement to in-person care for children and adolescents with T1D and suboptimal glycemic control and can successfully improve HbA1c levels and adherence to recommended frequency of care in this high-risk clinical population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31455673

RESUMO

BACKGROUND: Fiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown. METHODS: The association between prebiotic use and colorectal cancer risk and mortality was evaluated in postmenopausal women in the Women's Health Initiative study. Self-reported prebiotic use was documented at study enrollment. Adjudicated colorectal cancer cases and mortality were captured using medical and death records. Cox proportional hazards models were used to estimate the HR related to prebiotic use and colorectal cancer risk and mortality. RESULTS: In total, 3,032 colorectal cancer cases were diagnosed during an average 15.4 years of follow-up. Overall, 3.7% of women used a prebiotic with psyllium, the major fiber type. Use of any prebiotic supplement was not associated with colorectal cancer risk or mortality. The type of prebiotic supplement (none vs. insoluble or soluble) was not associated with colorectal cancer risk; however, use of insoluble fiber prebiotics compared with none was associated with higher colorectal cancer mortality [HR, 2.79; 95% confidence interval (CI), 1.32-5.90; P = 0.007]. Likelihood ratio tests indicated no significant interactions between prebiotic use and other colorectal cancer risk factors, including metabolic syndrome. CONCLUSIONS: Prebiotic fiber supplement use was not associated with colorectal cancer risk. Insoluble, but not soluble, prebiotic fiber use was associated with higher colorectal cancer mortality. These findings do not support the promotion of prebiotic fiber supplements to reduce colorectal cancer risk or colorectal cancer mortality. IMPACT: Further investigation is warranted for findings regarding insoluble prebiotic fiber and higher colorectal cancer mortality in postmenopausal women.

6.
Ann Am Thorac Soc ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31314549

RESUMO

Small pulmonary nodules are most often managed by surveillance imaging with chest computed tomography (CT), but the optimal frequency and duration of surveillance are unknown. The Watch the Spot Trial is a multi-center, pragmatic, comparative effectiveness trial with cluster randomization by hospital or health system that compares more vs. less intensive strategies for active surveillance of small pulmonary nodules. The study plans to enroll approximately 35,200 patients with a small pulmonary nodule that is newly detected on chest CT, either incidentally or by screening. Study protocols for more and less intensive surveillance were adapted from published guidelines. The primary outcome is the percentage of cancerous nodules that progress beyond American Joint Committee on Cancer 7th edition (AJCC 7) stage T1aN0M0. Secondary outcomes include patient-reported anxiety and emotional distress, nodule-related health care utilization, radiation exposure, and adherence with the assigned surveillance protocol. Distinctive aspects of the trial include: (1) the pragmatic integration of study procedures into existing clinical workflow; (2) the use of cluster-randomization by hospital or health system; (3) the implementation and evaluation of a system-level intervention for protocol-based care; (4) the use of highly efficient, technology-enabled methods to identify and (passively) enroll participants; (5) reliance on data collected as part of routine clinical care, including data from electronic health records and state cancer registries; (6) linkage with state cancer registries for complete ascertainment of the primary study outcome; and (7) intensive engagement with a diverse group of patient and non-patient stakeholders in the design and execution of the study.

7.
Sci Total Environ ; 654: 1179-1186, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30841392

RESUMO

Fine particles (PM2.5) are known to increase risks of cardiovascular diseases, but it is unclear how they affect plasma lipid levels. In this study, we examined the associations between PM2.5 exposure and lipid/lipoprotein levels from 2289 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation. The average exposure to PM2.5 and gaseous co-pollutants during the prior one year, six months, 30 days, and one day were estimated for each woman based on U.S. Environmental Protection Agency ambient monitoring data. Blood samples were collected annually from 1999 to 2005 and analyzed for lipids/lipoproteins. Mixed-effect models were used to account for repeated measures for each woman, adjusted for demographic, health and behavior covariates. PM2.5 exposures, especially the long-term exposure, were negatively associated with protective lipoproteins, and positively associated with atherogenic lipoproteins. For example, each 3 µg/m3 increase of one-year PM2.5 exposure was associated with decreases of -0.7% (-1.4%, -0.1%) in high-density lipoprotein cholesterols and -0.6% (-1.1%, -0.1%) in apolipoprotein A1 (ApoA1), as well as increases of 3.8% (1.0%, 6.6%) in lipoprotein(a) and 1.4% (0.5%, 2.3%) in the ratio of apolipoprotein B (ApoB)/ApoA1. In stratified analysis, increased atherogenic lipoproteins were mainly observed in women without dyslipidemia, and both increased atherogenic lipoproteins and reduced protective lipoproteins were observed among women in perimenopause. In summary, PM2.5 exposure was associated with adverse lipid level changes, and thus, may increase cardiovascular risks in midlife women.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Material Particulado/análise , HDL-Colesterol , Lipoproteínas , Estudos Longitudinais , Estados Unidos
8.
Psychometrika ; 84(2): 447-467, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30877425

RESUMO

The inverse probability of treatment weighted (IPTW) estimator can be used to make causal inferences under two assumptions: (1) no unobserved confounders (ignorability) and (2) positive probability of treatment and of control at every level of the confounders (positivity), but is vulnerable to bias if by chance, the proportion of the sample assigned to treatment, or proportion of control, is zero at certain levels of the confounders. We propose to deal with this sampling zero problem, also known as practical violation of the positivity assumption, in a setting where the observed confounder is cluster identity, i.e., treatment assignment is ignorable within clusters. Specifically, based on a random coefficient model assumed for the potential outcome, we augment the IPTW estimating function with the estimated potential outcomes of treatment (or of control) for clusters that have no observation of treatment (or control). If the cluster-specific potential outcomes are estimated correctly, the augmented estimating function can be shown to converge in expectation to zero and therefore yield consistent causal estimates. The proposed method can be implemented in the existing software, and it performs well in simulated data as well as with real-world data from a teacher preparation evaluation study.

9.
J Am Heart Assoc ; 8(4): e011021, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30764690

RESUMO

Background Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25-hydroxy vitamin D (25[ OH ]D) rather than total 25( OH )D may explain apparent racial disparities in cardiovascular disease ( CVD ). We prospectively examined black-white differences in the associations of total, free, and bioavailable 25( OH )D, vitamin D-binding protein, and parathyroid hormone levels at baseline with incident CVD (including nonfatal myocardial infarction, nonfatal stroke, and CVD death) in postmenopausal women. Methods and Results We conducted a case-cohort study among 79 705 postmenopausal women, aged 50 to 79 years, who were free of CVD at baseline in the WHI-OS (Women's Health Initiative Observational Study). A subcohort of 1300 black and 1500 white participants were randomly chosen as controls; a total of 550 black and 1500 white women who developed incident CVD during a mean follow-up of 11 years were chosen as cases. We directly measured total 25( OH )D, vitamin D-binding protein, albumin, parathyroid hormone, and calculated free and bioavailable 25( OH )D. Weighted Cox proportional hazards models were used to examine their associations with CVD risk. Although vitamin D-binding protein and total, free, and bioavailable 25( OH )D were not significantly associated with CVD risk in black or white women, a significant positive association between parathyroid hormone and CVD risk persisted in white women (hazard ratio comparing the highest quartile with the lowest, 1.37; 95% CI , 1.06-1.77) but not in black women (hazard ratio comparing the highest quartile with the lowest, 1.12; 95% CI, 0.79-1.58), independent of total, free, and bioavailable 25( OH )D or vitamin D-binding protein. Conclusions Circulating levels of vitamin D biomarkers are not related to CVD risk in either white or black women. Higher parathyroid hormone levels may be an independent risk factor for CVD in white women.

10.
Int J Cancer ; 145(8): 2051-2060, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30684389

RESUMO

Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC-MS/MS assays, we evaluated associations between pre-diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency-matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI-OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n = 102 serous/67 non-serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone-glucuronide (ADT-G) and total 5-α reduced glucuronide metabolites (markers of tissue-level androgenic activity) were at increased risk of developing non-serous ovarian cancer: ADT-G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68-11.32), p-heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47-8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT-G and total glucuronide metabolites, better markers of tissue-level androgenic activity in women than testosterone, were associated with an increased risk of developing non-serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non-serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer.

11.
Cancer ; 125(7): 1133-1142, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548236

RESUMO

BACKGROUND: The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size. METHODS: Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person's 30s. RESULTS: Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022). CONCLUSIONS: Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.

12.
Am J Epidemiol ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407487

RESUMO

Lifestyle-related factors influence risk of endometrial and ovarian cancers, but few studies have examined their joint associations with risk of these cancers. Using multivariable Cox regression models, we assessed the association of a healthy lifestyle index ((HLI) - a composite score (range 0-20) involving diet, alcohol consumption, physical activity, body mass index and smoking; higher scores represent healthier behavior) - with risk of endometrial and ovarian cancers among 108,136 postmenopausal women who were recruited in the Women's Health Initiative study between 1993 and 1998. After a median follow-up of 17.9 years, 1,435 endometrial cancer cases and 904 ovarian cancer cases had been ascertained. Women in the highest quintile of the HLI score had a lower risk of overall, Type I, well-differentiated, moderately differentiated, poorly differentiated, and localized endometrial cancer than those in the lowest quintile (HR≥q5 vs q1: 0.61 (95% CI: 0.51,0.72), 0.60 (0.49.0.72), 0.66 (0.46, 0.96), 0.69 (0.52,0.90), 0.49 (0.34,0.72) and 0.61 (0.50,0.74), respectively). The HLI score had a weak positive association with risk of serous ovarian cancer. Our findings underscore the potential importance of a healthy lifestyle in lowering endometrial cancer risk among postmenopausal women.

13.
J Hematol Oncol ; 11(1): 129, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400986

RESUMO

BACKGROUND: This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. METHOD: Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans. RESULTS: FoundationACT detected GAs in 69 of 81 (85%) cases with MSAF > 0. Forty-two of 51 (82%) cases had ≥ 1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N = 81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P = 0.0006) or high tumor metabolic burden (P = 0.0006) regardless of cfDNA quantity (P = 0.2362). CONCLUSION: This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden.

14.
mSphere ; 3(6)2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30404934

RESUMO

In 2017, a new type of goose-origin astrovirus (GoAstV) that is completely different from previously identified avian astroviruses (which have only 30.0% to 50.5% homology with GoAstV) has been isolated from diseased geese in China. This disease can cause joint swelling in sick geese, and the anatomy shows a clear precipitation of urate in the kidney. The rate of death and culling can reach more than 30%, revealing the disease's severe pathogenicity. To quickly and accurately diagnose the newly emerging disease, we established a highly specific reverse transcription-quantitative PCR (RT-qPCR) method of detecting GoAstV. Sensitivity testing showed that the minimum amount of test sample for this method is 52.5 copies/µl. Clinical application confirmed that this method can quickly and effectively detect GoAstV, providing a diagnostic platform for the prevention and control of goose disease.IMPORTANCE Goose-origin astrovirus (GoAstV), as a newly emerging virus in 2017, is different from previously known astroviruses in the genus Avastrovirus So far, few studies have focused on the novel virus. Considering the infectious development of astrovirus (AstV), we established a reverse transcription-quantitative PCR (RT-qPCR) assay with a strong specificity to quickly and accurately diagnose GoAstV. Confirmed by clinical application, this method can quickly and accurately detect prevalent GoAstV. The assay is thus convenient for clinical operation and is applicable to the monitoring of GoAstV disease.

15.
Sleep Med ; 50: 48-54, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29982090

RESUMO

BACKGROUND/OBJECTIVE: Many studies have shown a U-shaped association of sleep duration with mortality; however, this association is difficult to interpret owing to possible reverse causation, residual confounding, and measurement issues. We used data from the Women's Health Initiative to examine the associations of sleep duration, insomnia, and use of sleep aids with death from cardiovascular disease (CVD), cancer, "other" causes, and all causes combined. METHODS: Cox proportional hazards models were used in the analysis of baseline data and in time-dependent analyses of repeated measures to estimate associations of sleep-related factors with mortality. Among 158,203 women with information regarding sleep, 30,400 total deaths, 8857 CVD deaths, 9284 cancer deaths, and 11,928 other deaths were ascertained over a median of 17.8 years. RESULTS: In both baseline and time-dependent analyses, both short (≤5 h) and long sleep (≥9 h) durations were associated with increased risk of total, CVD, and "other" deaths, but not with cancer deaths. Insomnia showed no association with mortality, whereas use of sleep medications was associated with an increased mortality risk. CONCLUSIONS: While our findings showed a small but robust association of sleep duration with mortality in postmenopausal women, studies including objective measurements of sleep quality and efficiency are needed to clarify these associations.

16.
Stat Med ; 37(24): 3417-3436, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29943474

RESUMO

Missing covariates often occur in biomedical studies with survival outcomes. Multiple imputation via chained equations (MICE) is a semi-parametric and flexible approach that imputes multivariate data by a series of conditional models, one for each incomplete variable. When applying MICE, practitioners tend to specify the conditional models in a simple fashion largely dictated by the software, which could lead to suboptimal results. Practical guidelines for specifying appropriate conditional models in MICE are lacking. Motivated by a study of time to hip fractures in the Women's Health Initiative Observational Study using accelerated failure time models, we propose and experiment with some rationales leading to appropriate MICE specifications. This strategy starts with specifying a joint model for the variables involved. We first derive the conditional distribution of each variable under the joint model, then approximate these conditional distributions to the extent which can be characterized by commonly used regression models. We propose to fit separate models to impute incomplete variables by the failure status, which is key to generating appropriate MICE specifications for survival outcomes. The proposed strategy can be conveniently implemented with all available imputation software that uses fully conditional specifications. Our simulation results show that some commonly used simple MICE specifications can produce suboptimal results, while those based on the proposed strategy appear to perform well and be robust toward model misspecifications. Hence, we warn against a mechanical use of MICE and suggest careful modeling of the conditional distributions of variables to ensure proper performance.

17.
Menopause ; 25(10): 1131-1137, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29762199

RESUMO

OBJECTIVE: We conducted a gene-environment interaction study to evaluate whether the association of body mass index (BMI) associated meta genome-wide association study single-nucleotide polymorphisms (SNPs) (as a genetic risk score) and BMI is modified by physical activity and age. METHODS: In 8,206 women of European ancestry from the Women's Health Initiative (WHI), we used linear regression to examine main effects of the 95 SNP BMI genetic risk score (GRS) and physical activity on BMI, and evaluated whether genetic associations are modified by physical activity (two-way interaction) and age (three-way interaction). RESULTS: We found evidence for modification of the BMI GRS-BMI association according to both physical activity and age. We observed a significant two-way interaction of BMI GRS × physical activity in the crude model (P interaction = 0.05), where a smaller effect of the BMI GRS on BMI with increasing physical activity. The beta coefficient was 0.05 (standard error [SE] = 0.02, P = 0.01) for the high-activity group compared with beta = 0.13 (SE = 0.02, P = 4.8 × 10) for the sedentary group. The three-way interaction was statistically significant (adjusted P interaction = 0.01). Notably, in the 70+ age group, the BMI GRS-BMI association was attenuated and no longer significant in the high-activity group; the beta coefficient for the 70+ high-activity group was relatively small and nonsignificant (beta = 0.02, SE = 0.03, P = 0.58) compared with 70+ sedentary group (beta = 0.17, SE = 0.03, P = 2.5 × 10). CONCLUSION: Our study suggests that physical activity attenuates the influence of genetic predisposition to obesity, and this effect is more profound in the oldest age group.

18.
Br J Cancer ; 118(12): 1639-1647, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29795306

RESUMO

BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

19.
JAMA Oncol ; 4(10): e181212, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800122

RESUMO

Importance: In a randomized clinical trial, a low-fat eating pattern was associated with lower risk of death after breast cancer. However, the extent to which results were driven by dietary influence on survival after breast cancer diagnosis was unknown. Objective: To determine the association of a low-fat dietary pattern with breast cancer overall survival (breast cancer followed by death from any cause measured from cancer diagnosis). Design, Setting, and Participants: This is a secondary analysis of the Women's Health Initiative randomized clinical trial that was conducted at 40 US clinical centers enrolling participants from 1993 through 1998. Participants were 48 835 postmenopausal women with no previous breast cancer and dietary fat intake of greater than 32% by food frequency questionnaire. Interventions: Participants were randomized to a dietary intervention group (40%; n = 19 541) with goals to reduce fat intake to 20% of energy and increase fruit, vegetable, and grain intake or a usual-diet comparison group (60%; n = 29 294). Dietary group participants with incident breast cancers continued to participate in subsequent dietary intervention activities. Main Outcomes and Measures: Breast cancer overall survival for incident breast cancers diagnosed during the 8.5-year (median) dietary intervention, examined in post hoc analyses after 11.5 years (median) postdiagnosis follow-up. Results: Of 1764 women diagnosed with breast cancer during the dietary intervention period, mean (SD) age at screening was 62.7 (6.7) years and age at diagnosis was 67.6 (6.9) years. With 516 total deaths, breast cancer overall survival was significantly greater for women in the dietary intervention group than in the usual-diet comparison group (10-year survival of 82% and 78%, respectively; hazard ratio [HR], 0.78; 95% CI, 0.65-0.94; P = .01). In the dietary group there were fewer deaths from breast cancer (68 vs 120; HR, 0.86; 95% CI, 0.64-1.17), other cancers (36 vs 65; HR, 0.76; 95% CI, 0.50-1.17), and cardiovascular disease (27 vs 64; HR, 0.62; 95% CI, 0.39-0.99). Conclusions and Relevance: In women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased overall survival. The increase is due, in part, to better survival from several causes of death. Trial Registration: ClinicalTrials.gov Identifier: NCT00000611.

20.
J Am Acad Dermatol ; 79(2): 221-229, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29653212

RESUMO

BACKGROUND: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. OBJECTIVE: To identify histomorphologic features correlating with BRAF V600E status in nevi. METHODS: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. RESULTS: Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. LIMITATIONS: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. CONCLUSIONS: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

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