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Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis., Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium., Setting: Population-based., Patient(s): We included 8,500 women with ovarian cancer, 13,592 control women., Intervention(s): Ten well-established ovarian cancer risk factors., Main Outcome Measure(s): Risk of ovarian cancer for women with and without endometriosis., Result(s): Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-<30 kg/m 2 was associated with increased ovarian cancer risk among women with endometriosis (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.00-1.60), but not associated with the risk among women without endometriosis (OR = 0.97; 95% CI, 0.91-1.05) when compared with BMI 18.5-<25 kg/m 2 ; an increased risk was observed for a BMI ≥30 kg/m 2 , although there was little difference comparing women with endometriosis (OR = 1.21; 95% CI, 0.94-1.57) to women without (OR = 1.13; 95% CI, 1.04-1.22) (P-interaction = .51). Genital talcum powder use and long-term menopausal estrogen-only therapy use showed increased ovarian cancer risk, but risk appeared greater for those with endometriosis vs. those without (genital talcum powder: OR = 1.38; 95% CI, 1.04-1.84 vs. OR = 1.12; 95% CI, 1.01-1.25, respectively; ≥10 years of estrogen-only therapy: OR = 1.88; 95% CI, 1.09-3.24 vs. OR = 1.42; 95% CI, 1.14-1.76, respectively); neither of these interactions were statistically significant (P-interaction = .65 and P-interaction = .96, respectively)., Conclusion(s): The associations between ovarian cancer and most risk factors were similar among women with and without endometriosis. However, there was some suggestion of differences by endometriosis status for BMI, menopausal hormone therapy use, and genital talcum powder use, highlighting the complexity of ovarian cancer etiology., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Diagnostic variation among pathologists interpreting cutaneous melanocytic lesions could lead to suboptimal care., Objective: To estimate the potential association of second-opinion strategies in the histopathologic diagnosis of cutaneous melanocytic lesions with diagnostic accuracy and 1-year population-level costs in the US., Design, Setting, and Participants: Decision analysis with 1-year time horizon including melanocytic lesion diagnoses available from US pathologists participating in the Melanoma Pathology Study (M-Path) and from the study panel of reference pathologists who classified cases using the MPATH-Dx classification tool. M-Path data collection occurred from July 2013 through March 2015; analyses for the present study were performed between April 2015 and January 2021., Exposures: Various second-opinion strategies for interpretation of melanocytic cutaneous lesions., Main Outcomes and Measures: Estimated accuracy of pathologists' diagnoses, defined as concordance with the reference panel diagnoses, and 1-year postbiopsy medical costs under various second-opinion strategies. Expected percentage of concordant diagnoses, including percentages of overinterpretation and underinterpretation, and 1-year costs of medical care per 100 000 in the US population., Results: Decision-analytic model parameters were based on diagnostic interpretations for 240 cases by 187 pathologists compared with reference panel diagnoses. Without second opinions, 83.2% of diagnoses in the US were estimated to be accurate-ie, concordant with the reference diagnosis; with overinterpretation (8.0%) or underinterpretation (8.8%), and 16 850 misclassified diagnoses per 100 000 biopsies. Accuracy increased under all second-opinion strategies. Accuracy (87.4% concordance with 3.6% overinterpretation and 9.1% underinterpretation) and cost (an increase of more than $10 million per 100 000 biopsies per year) were highest when second opinions were universal (eg, performed on all biopsies), relative to no second opinions. A selective second-opinion strategy based on pathologists' desire or institutional requirements for a second opinion was most accurate (86.5% concordance; 4.4% overinterpretation; 9.1% underinterpretation) and would reduce costs by more than $1.9 million per 100 000 skin biopsies relative to no second opinions. Improvements in diagnostic accuracy with all second-opinion strategies were associated with reductions in overinterpretation but not underinterpretation., Conclusions and Relevance: In this decision-analytic model, selective second-opinion strategies for interpretation of melanocytic skin lesions showed the potential to improve diagnostic accuracy and decrease costs relative to no second opinions or universal second opinions.

Background: Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered., Methods: The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case-control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted., Results: Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50-0.85). There was a statistically significant trend of decreasing risk with increasing duration of use ( P trend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk., Conclusions: DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted., Impact: The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect., (©2021 American Association for Cancer Research.)

Endometriosis is a common gynecologic disease defined by the presence of endometrial-like tissue outside the uterine cavity. While its etiology is largely unknown, accumulating evidence suggests that inflammation plays a major role. Our objective was to investigate the association between peripheral blood leukocyte telomere length (LTL) and endometriosis using data from two large population-based studies, the New England Case-Control Study (NEC; n = 877) and the National Health and Nutrition Examination Survey (NHANES; n = 2268). NEC control participants were identified through a combination of random digit dialing, drivers' license lists, and town resident lists. In NHANES, selection algorithms were used to identify a nationally representative sample. Blood samples and demographic, reproductive, and health-related information were available from both data sources. Endometriosis was defined as self-reported of physician-diagnosed endometriosis. LTL was measured using quantitative polymerase chain reaction. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between LTL and endometriosis. Shorter LTL was associated with greater odds of history of endometriosis. In NEC, women with the shortest LTL tertile compared with the longest had a 2.5-fold greater odds of endometriosis (OR T3/T1  = 2.56, 95% CI = 1.16-5.63; p value, test for linear trend = 0.02). The association was stronger among women who usually experienced moderate or severe menstrual pain (OR T3/T1  = 3.50, 95% CI = 1.12-10.97). In NHANES, the data suggested a similar but attenuated association (OR T3/T1  = 1.29, 95% CI = 0.85-1.96). The observed associations in NEC suggest that shorter LTL may be associated with greater odds of endometriosis. A better understanding of how LTL influences endometriosis risk could elucidate novel disease pathophysiology.

Importance: Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent., Objective: To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype., Design, Setting, and Participants: A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019., Exposures: Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies., Main Outcomes and Measures: Diagnosis of epithelial ovarian cancer., Results: A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02)., Conclusions and Relevance: Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.

Background: Fast food is cross-sectionally associated with having overweight and obesity in young children., Objectives: To examine whether fast food intake independently contributes to the development of overweight and obesity among preschool-age children., Methods: Prospective cohort of 3- to 5-year-old children (n = 541) followed for 1 year. Children's height and weight were objectively measured at baseline and study end. Parents reported their child's fast food intake frequency in the past week from 11 chain fast food restaurants in six online follow-up surveys, completed approximately 8 weeks apart. Poisson regression with robust standard errors modelled the risk of a child increasing in weight status (ie, transitioning from a having a healthy weight to having overweight or from having overweight to having obesity) over the study period in relation to their average weekly fast food intake, adjusted for sociodemographics, child obesogenic behaviours, and parent weight status., Results: At baseline, 18.1% of children had overweight and 9.8% had obesity; 8.1% of children transitioned to a greater weight status over the 1-year period. Mean fast food intake frequency among consumers was 2.1 (SD: 1.4) times per week. The risk of increasing in weight status increased linearly with each additional time fast food was consumed in an average week over the study year (RR: 1.38; 95% CI, 1.13-1.67; P < .01)., Conclusions: Greater fast food intake over 1 year was associated with increasing weight status during that time in this preschool-age cohort., (© 2020 World Obesity Federation.)

Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker., Methods: We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC., Result: The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset., Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

Introduction: Fast food (FF) advertising is a potential risk factor for FF consumption among children, yet the impact of such advertising on children's FF intake has not been assessed in a longitudinal, naturalistic study. Whether parents' FF consumption mitigates advertising effects is also unknown., Methods: One-year, longitudinal study among 624 preschool-age children, 3-5 years old, and one parent each recruited from New Hampshire, 2014-2015. Parents completed six online surveys every eight weeks and, at each, reported the number of times their children consumed FF in the past week. Each child's advertisement exposure was determined by counting the brand-specific FF advertisements aired within the programs they viewed on children's TV networks during the study. At baseline, parents reported the frequency of their own FF consumption. Data were analyzed in 2017-2018., Results: Three FF brands targeted TV advertising to children during the study: McDonald's, Wendy's and Subway. Few children were exposed to child-targeted advertising for Wendy's or Subway. Results from adjusted Poisson regression models focused on McDonald's showed a differential effect of advertisement exposure on children's McDonald's intake in the past week (any or mean intake) by parental FF consumption (P < 0.01). Specifically, McDonald's intake was consistently high among children whose parents consumed FF more frequently (≥monthly), regardless of children's advertisement exposure. However, advertisement exposure increased the risk of McDonald's intake among children nearly two-fold when parents consumed FF less frequently (

Introduction: Child-directed TV advertising is believed to influence children's diets, yet prospective studies in naturalistic settings are absent. This study examined if child-directed TV advertisement exposure for ten brands of high-sugar breakfast cereals was associated with children's intake of those brands prospectively., Methods: Observational study of 624 preschool-age children and their parents conducted in New Hampshire, 2014-2015. Over 1 year, parents completed a baseline and six online follow-up surveys, one every 8 weeks. Children's exposure to high-sugar breakfast cereal TV advertisements was based on the network-specific TV programs children watched in the 7 days prior to each follow-up assessment, and parents reported children's intake of each advertised high-sugar breakfast cereal brand during that same 7-day period. Data were analyzed in 2017-2018., Results: In the fully adjusted Poisson regression model accounting for repeated measures and brand-specific effects, children with high-sugar breakfast cereal advertisement exposure in the past 7 days (i.e., recent exposure; RR=1.34, 95% CI=1.04, 1.72), at any assessment in the past (RR=1.23, 95% CI=1.06, 1.42), or recent and past exposure (RR=1.37, 95% CI=1.15, 1.63) combined had an increased risk of brand-specific high-sugar breakfast cereal intake. Absolute risk difference of children's high-sugar breakfast cereal intake because of high-sugar breakfast cereal TV advertisement exposure varied by brand., Conclusions: This naturalistic study demonstrates that child-directed high-sugar breakfast cereal TV advertising was prospectively associated with brand-specific high-sugar breakfast cereal intake among preschoolers. Findings indicate that child-directed advertising influences begin earlier and last longer than previously demonstrated, highlighting limitations of current industry guidelines regarding the marketing of high-sugar foods to children under age 6 years., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The impact of malpractice concerns on pathologists' use of defensive medicine and interpretations of melanocytic skin lesions (MSLs) is unknown., Methods: A total of 207 pathologists interpreting MSLs responded to a survey about past involvement in malpractice litigation, influence of malpractice concerns on diagnosis, and use of assurance behaviors (defensive medicine) to alleviate malpractice concerns. Assurance behaviors included requesting second opinions, additional slides, additional sampling, and ordering specialized tests., Results: Of the pathologists, 27.5% reported that malpractice concerns influenced them toward a more severe MSL diagnosis. Nearly all (95.2%) pathologists reported practicing at least one assurance behavior due to malpractice concerns, and this practice was associated with being influenced toward a more severe MSL diagnosis (odds ratio, 2.72; 95% confidence interval, 1.41-5.26)., Conclusions: One of four US skin pathologists upgrade MSL diagnosis due to malpractice concerns, and nearly all practice assurance behaviors. Assurance behaviors are associated with rendering a more severe MSL diagnosis.

Background: Diagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear., Objective: Identify pathologist characteristics associated with rates of accuracy and reproducibility., Methods: Pathologists independently interpreted the same set of biopsy specimens from melanocytic lesions on 2 occasions. Diagnoses were categorized into 1 of 5 classes according to the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis system. Reproducibility was determined by pathologists' concordance of diagnoses across 2 occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models., Results: Rates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology and in those with 5 or more years of experience. In addition, accuracy was high among pathologists with a higher proportion of melanocytic lesions in their caseload composition and higher volume of melanocytic lesions., Limitations: Data gathered in a test set situation by using a classification tool not currently in clinical use., Conclusion: Diagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact of these referrals on patient outcomes requires additional research., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The recently updated American Joint Committee on Cancer (AJCC) classification of cancer staging, the AJCC Cancer Staging Manual , 8th edition ( AJCC 8 ), includes revisions to definitions of T1a vs T1b or greater. The Melanoma Pathology Study database affords a comparison,of pathologists' concordance and reproducibility in the microstaging of melanoma according to both the existing 7th edition (AJCC 7 ) and the new AJCC 8 ., Objective: To compare AJCC 7 and AJCC 8 to examine whether changes to the definitions of T1a and T1b or greater are associated with changes in concordance and reproducibility., Design Setting and Participants: In this diagnostic study conducted as part of the national Melanoma Pathology Study across US states, 187 pathologists interpreting melanocytic skin lesions in practice completed 4342 independent case interpretations of 116 invasive melanoma cases. A consensus reference diagnosis and participating pathologists' interpretations were classified into the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis class IV (T1a) or class V ( T1b) using both the AJCC 7 and AJCC 8 criteria., Main Outcomes and Measures: Concordance with consensus reference diagnosis, interobserver reproducibility, and intraobserver reproducibility., Results: For T1a diagnoses, participating pathologists' concordance with the consensus reference diagnosis increased from 44% (95% CI, 41%-48%) to 54% (95% CI, 51%-57%) using AJCC 7 and AJCC 8 criteria, respectively. The concordance for cases of T1b or greater increased from 72% (95% CI, 69%-75%) to 78% (95% CI, 75%-80%). Intraobserver reproducibility of diagnoses also improved, increasing from 59% (95% CI, 56%-63%) to 64% (95% CI, 62%-67%) for T1a invasive melanoma, and from 74% (95% CI, 71%-76%) to 77% (95% CI, 74%-79%) for T1b or greater invasive melanoma cases., Conclusions and Relevance: Melanoma staging in AJCC 8 shows greater reproducibility and higher concordance with a reference standard. Improved classification of invasive melanoma can be expected after implementation of AJCC 8 , suggesting a positive impact on patients. However, despite improvement, concordance and reproducibility remain low., Competing Interests: Conflict of Interest Disclosures: Dr Elder reported serving as a consultant for Myriad Genetics and SciBase and receiving research funding from the National Institutes of Health/National Cancer Institute. Dr Barnhill reported a financial relationship with Myriad Genetics. Dr Longton reported receiving grants from Fred Hutchinson Cancer Research Center and the National Cancer Institute during the conduct of the study. Drs Titus, Weinstock, Pepe, and Piepkorn reported receiving grants from the National Cancer Institute during the conduct of the study. No other disclosures were reported.

Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association between severe menstrual pain and ovarian cancer, adjusting for potential confounders and multinomial logistic regression to calculate ORs for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct question, severe pain was associated with a small but significant increase in overall risk of ovarian cancer (OR = 1.07, 95% CI: 1.01-1.13), after adjusting for endometriosis and other potential confounders. The association appeared to be more relevant for clear cell (OR = 1.48, 95% CI: 1.10-1.99) and serous borderline (OR = 1.31, 95% CI: 1.05-1.63) subtypes. In this large international pooled analysis of case-control studies, we observed a small increase in risk of ovarian cancer for women reporting severe menstrual pain. While we observed an increased ovarian cancer risk with severe menstrual pain, the possibility of recall bias and undiagnosed endometriosis cannot be excluded. Future validation in prospective studies with detailed information on endometriosis is needed., (© 2017 UICC.)

Background: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited., Objective: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions., Materials and Methods: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions., Results: Laboratory policies required second opinions for 31% of pathologists and most commonly required for melanoma in situ (26%) and invasive melanoma (30%). In practice, most pathologists reported requesting second opinions for melanocytic tumors of uncertain malignant potential (85%) and atypical Spitzoid lesions (88%). Most pathologists perceived that second opinions increased interpretive accuracy (78%) and protected them from malpractice lawsuits (62%)., Conclusion: Use of second opinions in clinical practice is greater than that required by laboratory policies, especially for melanocytic tumors of uncertain malignant potential and atypical Spitzoid lesions. Quality of care in surgical interventions for atypical melanocytic proliferations critically depends on the accuracy of diagnosis in pathology reporting. Future research should examine the extent to which second opinions improve accuracy of melanocytic lesion diagnosis.

Background: Little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time., Objectives: To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis., Methods: We conducted a before-and-after multiple time series study of Medicare beneficiaries aged ≥ 66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results Medicare database. Primary exposure was time from primary melanoma diagnosis at 3-6 months and 6-24 months postdiagnosis. Covariates included tumour-, patient- and geographical-level characteristics and healthcare utilization in the 6 months before diagnosis. Poisson regression was used to estimate population-based risk-adjusted utilization rates for skin biopsies, benign skin excisions, internal medicine office visits and dermatology office visits., Results: The study population included 56 254 patients with first diagnoses of primary melanoma. Most patients were ≥ 75 years old (56·8%), male (62·1%), and had in situ melanoma (42·4%) or localized invasive melanoma (45·9%). From 2000 to 2009, risk-adjusted skin biopsy rates 24 months postdiagnosis increased from 358·3 to 541·3 per 1000 person-years (P < 0·001), and dermatology visits increased from 989·0 to 1535·6 per 1000 person-years (P < 0·001). Benign excisions and internal medicine visits remained stable. In 2000, risk-adjusted skin biopsy rates 6 months postdiagnosis increased by 208·5 relative to the 6 months before diagnosis (148·7 vs. 357·2) compared with an observed absolute increase of 272·5 (290·9 vs. 563·1) in 2009. Trends in dermatology visits were similar., Conclusions: Utilization of skin biopsies and dermatology office visits following primary melanoma diagnosis has increased substantially over time. These results may inform optimization of care delivery for melanoma within the Medicare population., (© 2017 British Association of Dermatologists.)

Objective: To determine whether exposure to child-targeted fast-food (FF) television (TV) advertising is associated with children's FF intake in a non-experimental setting., Design: Cross-sectional survey conducted April-December 2013. Parents reported their pre-school child's TV viewing time, channels watched and past-week FF consumption. Responses were combined with a list of FF commercials (ads) aired on children's TV channels during the same period to calculate children's exposure to child-targeted TV ads for the following chain FF restaurants: McDonald's, Subway and Wendy's (MSW)., Setting: Paediatric and Women, Infants, and Children (WIC) clinics in New Hampshire, USA., Subjects: Parents (n 548) with a child of pre-school age., Results: Children's mean age was 4·4 years; 43·2 % ate MSW in the past week. Among the 40·8 % exposed to MSW ads, 23·3 % had low, 34·2 % moderate and 42·5 % high exposure. McDonald's accounted for over 70 % of children's MSW ad exposure and consumption. Children's MSW consumption was significantly associated with their ad exposure, but not overall TV viewing time. After adjusting for demographics, socio-economic status and other screen time, moderate MSW ad exposure was associated with a 31 % (95 % CI 1·12, 1·53) increase and high MSW ad exposure with a 26 % (95 % CI 1·13, 1·41) increase in the likelihood of consuming MSW in the past week. Further adjustment for parent FF consumption did not change the findings substantially., Conclusions: Exposure to child-targeted FF TV advertising is positively associated with FF consumption among children of pre-school age, highlighting the vulnerability of young children to persuasive advertising and supporting recommendations to limit child-directed FF marketing.

Background: Melanoma incidence has increased in recent decades in the U.S.A. Uncertainty remains regarding how much of this increase is attributable to greater melanoma screening activities, potential detection bias and overdiagnosis., Objectives: To use a cross-sectional ecological analysis to evaluate the relationship between skin biopsy and melanoma incidence rates over a more recent time period than prior reports., Methods: Examination of the association of biopsy rates and melanoma incidence (invasive and in situ) in SEER-Medicare data (including 10 states) for 2002-2009., Results: The skin biopsy rate increased by approximately 50% (6% per year) throughout this 8-year period, from 7012 biopsies per 100 000 persons in 2002 to 10 528 biopsies per 100 000 persons in 2009. The overall melanoma incidence rate increased approximately 4% (< 1% per year) over the same time period. The incidence of melanoma in situ increased approximately 10% (1% per year), while the incidence of invasive melanoma increased from 2002 to 2005 then decreased from 2006 to 2009. Regression models estimated that, on average, for every 1000 skin biopsies performed, an additional 5·2 (95% confidence interval 4·1-6·3) cases of melanoma in situ were diagnosed and 8·1 (95% confidence interval 6·7-9·5) cases of invasive melanoma were diagnosed. When considering individual states, some demonstrated a positive association between biopsy rate and invasive melanoma incidence, others an inverse association, and still others a more complex pattern., Conclusions: Increased skin biopsies over time are associated with increased diagnosis of in situ melanoma, but the association with invasive melanoma is more complex., (© 2016 British Association of Dermatologists.)

Long and irregular menstrual cycles, a hallmark of polycystic ovary syndrome (PCOS), have been associated with higher androgen and lower sex hormone binding globulin levels and this altered hormonal environment may increase the risk of specific histologic subtypes of ovarian cancer. We investigated whether menstrual cycle characteristics and self-reported PCOS were associated with ovarian cancer risk among 2,041 women with epithelial ovarian cancer and 2,100 controls in the New England Case-Control Study (1992-2008). Menstrual cycle irregularity, menstrual cycle length, and PCOS were collected through in-person interview. Unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for ovarian cancer risk overall, and polytomous logistic regression to evaluate whether risk differed between histologic subtypes. Overall, we observed no elevation in ovarian cancer risk for women who reported periods that were never regular or for those reporting a menstrual cycle length of >35 days with ORs of 0.87 (95% CI = 0.69-1.10) and 0.83 (95% CI = 0.44-1.54), respectively. We observed no overall association between self-reported PCOS and ovarian cancer (OR = 0.97; 95% CI = 0.61-1.56). However, we observed significant differences in the association with menstrual cycle irregularity and risk of ovarian cancer subtypes (p heterogeneity  = 0.03) as well as by BMI and OC use (p interaction  < 0.01). Most notable, menstrual cycle irregularity was associated with a decreased risk of high grade serous tumors but an increased risk of serous borderline tumors among women who had never used OCs and those who were overweight. Future research in a large collaborative consortium may help clarify these associations., (© 2016 UICC.)

Breakfast cereals represent the most highly advertised packaged food on child-targeted television, and most ads are for cereals high in sugar. This study examined whether children's TV exposure to child-targeted, high-sugar breakfast cereal (SBC) ads was associated with their consumption of those SBC brands. Parents of 3- to 5-year-old children were recruited from pediatric and Women, Infants, and Children (WIC) clinics in Southern New Hampshire, USA, and completed a cross-sectional survey between April-December 2013. Parents reported their child's consumption of SBC brands; whether their child had watched any of 11 kids' channels in the past week; their child's TV viewing time; and socio-demographics. Children's exposure to child-targeted SBC TV ads was calculated by combining TV channel and viewing time with advertising data for SBC ads aired on kids' TV channels during the same timeframe. Five hundred forty-eight parents completed surveys; 52.7% had an annual household income of $50,000 or less. Children's mean age was 4.4 years, 51.6% were female, and 72.5% were non-Hispanic white. In the past week, 56.9% (N = 312) of children ate SBCs advertised on kids' channels. Overall, 40.6% of children were exposed to child-targeted SBC TV ads in the past week. In fully adjusted analyses, the number of SBC brands children consumed was positively associated with their exposure to child-targeted SBC ads. Children consumed 14% (RR = 1.14, 95% CI: 1.02, 1.27) more SBC brands for every 10 SBC ads seen in the past 7 days. Exposure to child-targeted SBC TV advertising is positively associated with SBC brand consumption among preschool-aged children. These findings support recommendations to limit the marketing of high-sugar foods to young children., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Multiple studies of ovarian cancer and genital talc use have led only to consensus about possible carcinogenicity. Seeking greater clarity, we examined this association in 2,041 cases with epithelial ovarian cancer and 2,100 age- and-residence-matched controls., Methods: We defined genital talc use as regular application to the genital/rectal area directly, on sanitary napkins, tampons, or underwear. To estimate "talc-years," we multiplied applications per year by years used. Unconditional logistic regression, Wald statistics, likelihood-ratio tests, and polytomous logistic regression were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI), trends, effect-modification, and heterogeneity by ovarian cancer histologic subtype., Results: Overall, genital talc use was associated with an OR (95% CI) of 1.33 (1.16, 1.52), with a trend for increasing risk by talc-years. Women who used talc were more likely to be older, heavier, asthma sufferers, and regular analgesic users--none of which was a confounder. Dose-responses were more apparent for premenopausal women, especially nonsmokers and those heavier or postmenopausal users of menopausal hormones (hormone therapy [HT]). Subtypes of ovarian cancer more likely to be associated with talc included invasive serous and endometrioid tumors and borderline serous and mucinous tumors. Premenopausal women and postmenopausal HT users with these subtypes who had accumulated >24 talc-years had ORs (95% CI) of 2.33 (1.32, 4.12) and 2.57 (1.51, 4.36), respectively., Conclusion: Risks for epithelial ovarian cancer from genital talc use vary by histologic subtype, menopausal status at diagnosis, HT use, weight, and smoking. These observations suggest that estrogen and/or prolactin may play a role via macrophage activity and inflammatory response to talc.

Purpose: Cigarette smoking increases overall mortality, but it is not established whether smoking is associated with breast cancer prognosis., Methods: We evaluated the association between smoking status before and after breast cancer diagnosis and mortality in the Collaborative Breast Cancer and Women's Longevity Study, a population-based prospective observational study conducted in Wisconsin, New Hampshire, and Massachusetts. Participants included 20,691 women, ages 20 to 79 years, diagnosed with incident localized or regional invasive breast cancer between 1988 and 2008; a subset of 4,562 of these women were recontacted a median of 6 years after diagnosis. Hazard ratios (HRs) with 95% CIs were calculated according to smoking status for death as a result of breast cancer; cancers of the lung, pharynx, or intrathoracic organs; other cancer; respiratory disease; and cardiovascular disease., Results: During a median of 12 years, 6,778 women died, including 2,894 who died as a result of breast cancer. Active smokers 1 year before breast cancer diagnosis were more likely than never smokers to die of breast cancer (HR, 1.25; 95% CI, 1.13 to 1.37), respiratory cancer (HR, 14.48; 95% CI, 9.89 to 21.21), other respiratory disease (HR, 6.02; 95% CI, 4.55 to 7.97), and cardiovascular disease (HR, 2.08; 95% CI, 1.80 to 2.41). The 10% of women who continued to smoke after diagnosis were more likely than never smokers to die of breast cancer (HR, 1.72; 95% CI, 1.13 to 2.60). When compared with women who continued to smoke after diagnosis, those who quit smoking after diagnosis had lower mortality from breast cancer (HR, 0.67; 95% CI, 0.38 to 1.19) and respiratory cancer (HR, 0.39; 95% CI, 0.16 to 0.95)., Conclusion: Smoking before or after diagnosis was associated with a higher mortality from breast cancer and several other causes., (© 2016 by American Society of Clinical Oncology.)

Fast food restaurants spend millions of dollars annually on child-targeted marketing, a substantial portion of which is allocated to toy premiums for kids' meals. The objectives of this study were to describe fast food toy premiums, and examine whether young children's knowledge of fast food toy premiums was associated with their fast food consumption. Parents of 3- to 5-year old children were recruited from pediatric and WIC clinics in Southern New Hampshire, and completed a cross-sectional survey between April 2013-March 2014. Parents reported whether their children usually knew what toys were being offered at fast food restaurants, and whether children had eaten at any of four restaurants that offer toy premiums with kids' meals (McDonald's, Burger King, Subway, Wendy's) during the 7 days preceding the survey. Seventy-one percent of eligible parents participated (N = 583); 48.4% did not receive any education beyond high school, and 27.1% of children were non-white. Half (49.7%) the children had eaten at one or more of the four fast food restaurants in the past week; one-third (33.9%) had eaten at McDonald's. The four restaurants released 49 unique toy premiums during the survey period; McDonald's released half of these. Even after controlling for parent fast food consumption and sociodemographics, children were 1.38 (95% CI = 1.04, 1.82) times more likely to have consumed McDonald's if they usually knew what toys were offered by fast food restaurants. We did not detect a relationship between children's toy knowledge and their intake of fast food from the other restaurants. In this community-based sample, young children's knowledge of fast food toys was associated with a greater frequency of eating at McDonald's, providing evidence in support of regulating child-directed marketing of unhealthy foods using toys., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Concerns about breast cancer overdiagnosis have increased the need to understand how cancers detected through screening mammography differ from those first detected by a woman or her clinician. We investigated risk factor associations for invasive breast cancer by method of detection within a series of case-control studies (1992-2007) carried out in Wisconsin, Massachusetts, and New Hampshire (n=15,648 invasive breast cancer patients and 17,602 controls aged 40-79 years). Approximately half of case women reported that their cancer had been detected by mammographic screening and half that they or their clinician had detected it. In polytomous logistic regression models, parity and age at first birth were more strongly associated with risk of mammography-detected breast cancer than with risk of woman/clinician-detected breast cancer (P≤0.01; adjusted for mammography utilization). Among postmenopausal women, estrogen-progestin hormone use was predominantly associated with risk of woman/clinician-detected breast cancer (odds ratio (OR)=1.49, 95% confidence interval (CI): 1.29, 1.72), whereas obesity was predominantly associated with risk of mammography-detected breast cancer (OR=1.72, 95% CI: 1.54, 1.92). Among regularly screened premenopausal women, obesity was not associated with increased risk of mammography-detected breast cancer (OR=0.99, 95% CI: 0.83, 1.18), but it was associated with reduced risk of woman/clinician-detected breast cancer (OR=0.53, 95% CI: 0.43, 0.64). These findings indicate important differences in breast cancer risk factors according to method of detection., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

Purpose: Menstrual pain is associated with increased production of inflammatory molecules, such as prostaglandins. Inflammation is involved in pathogenesis of several cancers, including ovarian cancer. In this study, we examined the association between menstrual pain and risk of ovarian cancer., Methods: We conducted a case-control study with 2,028 cases of epithelial ovarian cancer and 2,091 age- and study center-matched controls. Women were asked to report the severity of menstrual pain during their twenties and thirties, when not using oral contraceptives or breastfeeding. We used an unconditional logistic regression to evaluate the association between menstrual pain and epithelial ovarian cancer risk overall, and polytomous logistic regression to evaluate whether the association differed across tumor subtypes., Results: Risk of ovarian cancer was increased in women with moderate (OR 1.22, 95 % CI 1.05-1.42) and severe pain (OR 1.34, 95 % CI 1.09-1.65) compared to women with no or mild pain during menstrual period. The association differed by histologic subtypes, with significant associations for severe pain with endometrioid (OR 1.64, 95 % CI 1.15-2.34) and clear cell tumors (OR 1.91, 95 % CI 1.11-3.28)., Conclusions: Our data suggest that moderate and severe pain during menstrual period are associated with increased risk of epithelial ovarian cancer. Due to high prevalence of menstrual pain in women of reproductive age, this observation warrants further studies.

Objective: The aim of this study is to examine whether school food attenuates household income-related disparities in adolescents' frequency of fruit and vegetable intake (FVI)., Method: Telephone surveys were conducted between 2007 and 2008 with adolescent-parent dyads from Northern New England; participants were randomly assigned to be surveyed at different times throughout the year. The main analysis comprised 1542 adolescents who typically obtained breakfast/lunch at school at least once/week. FVI was measured using 7-day recall of the number of times adolescents consumed fruits and vegetables. Fully adjusted linear regression was used to compare FVI among adolescents who were surveyed while school was in session (currently exposed to school food) to those who were surveyed when school was not in session (currently unexposed to school food)., Results: Mean FVI was 8.0 (SD=5.9) times/week. Among adolescents unexposed to school food, household income and FVI were strongly, positively associated. In contrast, among adolescents exposed to school food, FVI was similar across all income categories. We found a significant cross-over interaction between school food and household income in which consuming food at school was associated with higher FVI among adolescents from low-income households versus lower FVI among adolescents from high-income households., Conclusion: School food may mitigate income disparities in adolescent FVI. The findings suggest that the school food environment positively influences FVI among low-income adolescents., (Copyright © 2014. Published by Elsevier Inc.)

While several risk factors for breast cancer have been identified, studies have not consistently shown whether these factors operate more strongly at certain ages or for just pre- or postmenopausal women. We evaluated whether risk factors for breast cancer differ according to age or menopausal status. Data from five population-based case-control studies conducted during 1988-2008 were combined and analyzed. Cases (N = 23,959) and population controls (N = 28,304) completed telephone interviews. Logistic regression was used to estimate adjusted odds ratios and 95 % confidence intervals and tests for interaction by age and menopausal status. Odds ratios for first-degree family history of breast cancer were strongest for younger women-reaching twofold elevations-but were still statistically significantly elevated by 58-69 % among older women. Obesity was inversely associated with breast cancer among younger women and positively associated with risk for older women (interaction P < 0.0001). Recent alcohol intake was more strongly related to breast cancer risk among older women, although consumption of 3 or more drinks/day among younger women also was associated with elevated odd ratios (P < 0.0001). Associations with benign breast disease and most reproductive/menstrual factors did not vary by age. Repeating analysis stratifying by menopausal status produced similar results. With few exceptions, menstrual and lifestyle factors are associated with breast cancer risk regardless of age or menopausal status. Variation in the association of family history, obesity, and alcohol use with breast cancer risk by age and menopausal status may need to be considered when determining individual risk for breast cancer.

Purpose: The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk., Methods: We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N= 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models., Results: For standardized age at first birth, the OR was 1.52 (CI, 1.36-1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype., Conclusions: Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype., Methods: We evaluated fat intake in a New England case-control study including 1872 cases and 1978 population-based controls (1992-2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype., Results: We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66-0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64-0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08-1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41-0.82, P-trend=0.003)., Conclusions: These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.

Objective: To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival., Methods: We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models., Results: Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset., Conclusion: This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies., Methods: The first analysis was based on a sample of 1328 women age 20-74 who participated as controls in a case-control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43-86 recruited as part of a cohort study in Wisconsin., Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p=0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p=0.01). The results were not replicated in the validation cohort (B=-0.61, p=0.14 and B=-0.01, p=.0.98, respectively)., Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Previous studies have observed that tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer; however, little is known about whether these associations vary by surgical characteristics, individual characteristics or tumor histology. We used logistic regression to examine tubal ligation, simple hysterectomy and hysterectomy with unilateral oophorectomy in relation to risk of epithelial ovarian cancer in the New England Case-Control Study. Our primary analysis included 2,265 cases and 2,333 controls. Overall, tubal ligation was associated with a lower risk of epithelial ovarian cancer [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.68-0.97], especially for endometrioid tumors (OR = 0.45, 95% CI: 0.29-0.69). The inverse association between tubal ligation and ovarian cancer risk was stronger for women who had undergone the procedure at the time of last delivery (OR = 0.60, 95% CI: 0.42-0.84) rather than at a later time (OR = 0.93, 95% CI: 0.75-1.15). Overall, simple hysterectomy was not associated with ovarian cancer risk (OR: 1.09, 95% CI: 0.83-1.42), although it was associated with a nonsignificant decreased risk of ovarian cancer among women who underwent the procedure at age 45 or older (RR: 0.64, 95% CI: 0.40-1.02) or within the last 10 years (OR = 0.65, 95% CI: 0.38-1.13). Overall, women who had a hysterectomy with a unilateral oophorectomy had significantly lower risk of ovarian cancer (OR = 0.65, 95% CI: 0.45-0.94). In summary, tubal ligation and hysterectomy with unilateral oophorectomy were inversely associated with ovarian cancer risk in a large population-based case-control study. Additional research is necessary to understand the potential biologic mechanisms by which these procedures may reduce ovarian cancer risk., (Copyright © 2013 UICC.)

Background: Despite validation studies demonstrating substantial bias, epidemiologic studies typically use self-reported height and weight as primary measures of body mass index because of feasibility and resource limitations., Purpose: To demonstrate a method for calculating accurate and precise estimates that use body mass index when objectively measuring height and weight in a full sample is not feasible., Methods: As part of a longitudinal study of adolescent health, 1,840 adolescents (ages 12-18) self-reported their height and weight during telephone surveys. Height and weight was measured for 407 of these adolescents. Sex-specific, age-adjusted obesity status was calculated from self-reported and from measured height and weight. Prevalence and predictors of obesity were estimated using self-reported data, measured data, and multiple imputation (of measured data)., Results: Among adolescents with self-reported and measured data, the obesity prevalence was lower when using self-report compared with actual measurements (p < .001). The obesity prevalence from multiple imputation (20%) was much closer to estimates based solely on measured data (20%) compared with estimates based solely on self-reported data (12%), indicating improved accuracy. In multivariate models, estimates of predictors of obesity were more accurate and approximately as precise (similar confidence intervals) as estimates based solely on self-reported data., Conclusions: The two-method measurement design offers researchers a technique to reduce the bias typically inherent in self-reported height and weight without needing to collect measurements on the full sample. This technique enhances the ability to detect real, statistically significant differences, while minimizing the need for additional resources., (Copyright © 2013 Society for Adolescent Health and Medicine. All rights reserved.)

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score's highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67-2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.

Purpose: Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear., Patients and Methods: We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast cancer who were residents of Wisconsin, Massachusetts, or New Hampshire and diagnosed from 198 to 200 at ages 20 to 79 years. All women reported on prediagnostic intake; a subsample of 4,881 reported on postdiagnostic intake., Results: During a median follow-up of 11.3 years from diagnosis, 7,780 deaths occurred, including 3,484 resulting from breast cancer. Hazard ratios (HR) and 95% CIs were estimated. Based on a quadratic analysis, moderate alcohol consumption before diagnosis was modestly associated with disease-specific survival (compared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers., Conclusion: Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.

Study Question: Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification?, Summary Answer: Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer., What Is Known Already: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways., Design: This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews., Participants/materials, Setting, Methods: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center., Main Results and the Role of Chance: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility., Limitations, Reasons for Caution: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study., Wider Implications of the Findings: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types., Study Funding/competing Interest(s): This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare., Trial Registration Number: Not applicable.

Objectives: The 2010 Dietary Guidelines for Americans include reducing consumption of sugar-sweetened beverages. Among the many possible routes of access for youth, school vending machines provide ready availability of sugar-sweetened beverages. The purpose of this study was to determine variation in high school student access to sugar-sweetened beverages through vending machines by geographic location - urban, town or rural - and to offer an approach for analysing school vending machine content., Study Design: Cross-sectional observational study., Methods: Between October 2007 and May 2008, trained coders recorded beverage vending machine content and machine-front advertising in 113 machines across 26 schools in New Hampshire and Vermont, USA., Results: Compared with town schools, urban schools were significantly less likely to offer sugar-sweetened beverages (P = 0.002). Rural schools also offered more sugar-sweetened beverages than urban schools, but this difference was not significant. Advertisements for sugar-sweetened beverages were highly prevalent in town schools., Conclusions: High school students have ready access to sugar-sweetened beverages through their school vending machines. Town schools offer the highest risk of exposure; school vending machines located in towns offer up to twice as much access to sugar-sweetened beverages in both content and advertising compared with urban locations. Variation by geographic region suggests that healthier environments are possible and some schools can lead as inspirational role models., (Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: Genomewide association studies have consistently found variants in fibroblast growth factor receptor 2 (FGFR2) to be associated with breast cancer. Recent reports suggest that postmenopausal hormone therapy (HT) use may modify the association between single nucleotide polymorphisms (SNPs) in FGFR2 and breast cancer risk. We assessed the hypothesis that the association between rs1219648 (FGFR2) SNP and breast cancer risk is modified by postmenopausal HT use in a population-based case-control study., Methods: We evaluated rs1219648 SNP for an association with breast cancer risk using data obtained from 869 postmenopausal breast cancer cases diagnosed between 1995 and 2000 and from 808 postmenopausal community controls who participated in a study conducted in three US states. Detailed postmenopausal HT information was collected through a structured telephone interview, and DNA samples were collected by mail using an established mouthwash protocol. Odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for age and state of residence., Results: We observed a significant association between rs1219648 and breast cancer risk (per-allele odds ratio, 1.22; 95% CI, 1.06-1.41; P = 0.007), which did not vary significantly by ever use of estrogen plus progestogen therapy (interaction P = 0.48). There was stronger evidence of an interaction between ever use of estrogen-only HT and increasing number of rs1219648 risk alleles to increase breast cancer risk (interaction P = 0.08)., Conclusions: Our results are consistent with a risk association with FGFR2 but provide limited support for interaction with HT use. The study raises the possibility that the FGFR2 rs1219648 variant is more strongly associated with risk in estrogen-only hormone users, although this observation needs to be examined in larger studies.

Background: Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection., Objectives: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas., Methods: We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest., Results: Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor., Conclusions: Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case-control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium [Quartile 4 (Q4, >1,319 mg/day) vs. Quartile 1 (Q1, <655 mg/day), OR = 0.62, 95% CI = 0.49-0.79]; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline (Q4, >559 IU/day vs. Q1, <164 IU/day, OR = 0.51, 95% CI = 0.34-0.76) and endometrioid tumors (Q4 vs. Q1, OR = 0.55, 95% CI = 0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation., (Copyright © 2012 UICC.)

Introduction: Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women., Methods: We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingooophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific mortality were calculated using Cox proportional hazards regression., Results: Seventeen percent (N = 1,778) of breast cancer survivors (mean age at diagnosis = 63.5) reported pre-diagnosis TAHBSO. During follow-up (mean = 9.5 years), 2,856 deaths occurred, including 1,060 breast cancer deaths and 459 CVD deaths. Breast cancer deaths occurred a median of 5.1 years after diagnosis; CVD deaths occurred further from diagnosis (median = 9.7 years). Women who reported pre-diagnosis TAHBSO had a 16% decrease in all-cause mortality (HR = 0.84; 95% CI: 0.76, 0.92) compared to those with an intact uterus and ovaries. This overall decrease reflected a 27% lower breast cancer mortality among women who never used postmenopausal hormones (HR = 0.73; CI: 0.55, 0.96) and 43% lower CVD risk among women who reported using estrogen (HR = 0.57; CI: 0.39, 0.83) after TAHBSO., Conclusions: Information on prior TAHBSO and estrogen use can inform risk of death fromboth breast cancer and cardiovascular disease among breast cancer survivors.

Most studies of attention-deficit hyperactivity disorder (ADHD) youth have obtained data from the perspective of either children or parents, but not both simultaneously. The purpose of this study was to examine child and parent perspectives on parenting in a large community-based sample of children with and without ADHD. We identified children in grades 4-6 and their parents through surveys administered to a random sample of public schools. We used multivariable logistic regression to determine independent associations between child and parent characteristics and the presence of ADHD while controlling for covariates and clustering by school. Sufficient data were achieved for 2,509 child/parent dyads. Ten percent of youths (n = 240) had been diagnosed with ADHD. Compared with those without ADHD, those with ADHD were more commonly male (67.9 vs. 48.0 %, p < .001) and age 12 or over (16.3 vs. 10.3 %). After adjusting for covariates and clustering, compared to children without ADHD, children with ADHD were significantly more likely to report lower self-regulation (OR = 0.68, 95 % CI = 0.53, 0.88) and higher levels of rebelliousness (OR = 2.00, 95 % CI = 1.52, 2.69). Compared with parents whose children did not have ADHD, parents of children with ADHD rated their overall parental efficacy substantially lower (OR = 0.23, 95 % CI = 0.15, 0.33). However, child assessment of parenting style was similar by ADHD. Despite the internal challenges community-based youth with ADHD face, many parents of ADHD youth exhibit valuable parental skills from the perspective of their children. Feedback of this information to parents may improve parental self-efficacy, which is known to be positively associated with improved ADHD outcomes.

Objective: To compare the associations between weight status and different forms of physical activity among adolescents., Methods: We conducted telephone surveys with 1718 New Hampshire and Vermont high school students and their parents as part of a longitudinal study of adolescent health. We surveyed adolescents about their team sports participation, other extracurricular physical activity, active commuting, physical education, recreational activity for fun, screen time, diet quality, and demographics. Overweight/obesity (BMI for age ≥ 85th percentile) and obesity (BMI for age ≥ 95 percentile) were based on self-reported height and weight., Results: Overall, 29.0% (n = 498) of the sample was overweight/obese and 13.0% (n = 223) were obese. After adjustments, sports team participation was inversely related to overweight/obesity (relative risk [RR] = 0.73 [95% confidence interval (CI): 0.61, 0.87] for >2 sports teams versus 0) and obesity (RR = 0.61 [95% CI: 0.45, 0.81] for >2 sports teams versus 0). Additionally, active commuting to school was inversely related to obesity (RR = 0.67 [95% CI: 0.45, 0.99] for >3.5 days per week versus 0). Attributable risk estimates suggest obesity prevalence would decrease by 26.1% (95% CI: 9.4%, 42.8%) if all adolescents played on 2 sports teams per year and by 22.1% (95% CI: 0.1%, 43.3%) if all adolescents walked/biked to school at least 4 days per week., Conclusions: Team sport participation had the strongest and most consistent inverse association with weight status. Active commuting to school may reduce the risk of obesity, but not necessarily overweight, and should be studied further. Obesity prevention programs should consider strategies to increase team sport participation among all students.