Improving lifestyle behaviors during chemotherapy for breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) Trial.

BACKGROUND: Little is known about improving physical activity (PA) and diet during and after chemotherapy for breast cancer. This secondary analysis examines changes in PA and diet quality during a yearlong intervention for patients with breast cancer undergoing chemotherapy and evaluates factors associated with these changes. METHODS: Newly diagnosed patients with breast cancer (N = 173) undergoing chemotherapy were randomized to a year-long nutrition and exercise intervention (n = 87) or usual care (UC, n = 86). Mixed models compared 1-year changes in PA and diet quality via the Healthy Eating Index (HEI)-2015 by study arm. Among the intervention group, baseline factors associated with change in PA and diet were assessed with multivariable linear and logistic regression. RESULTS: At 1 year, compared with UC, the intervention arm increased PA more (mean difference = 136.1 minutes/week; 95% CI, 90.2-182.0), participated in more strength training (56% vs. 15%; p < .001), and had suggestive improvements in HEI-2015 (mean difference = 2.5; 95% CI, -0.3 to 5.3; p = .08). In the intervention arm, lower fatigue was associated with improved PA (p = .04) and higher education was associated with improved HEI-2015 (p = .001) at 1 year. Higher HEI-2015 (p = .04) and married/living with someone (p = .05) were associated with higher odds of participating in strength training at 1 year. CONCLUSIONS: This year-long lifestyle intervention for patients with breast cancer undergoing chemotherapy resulted in increases in PA and suggestive improvements in diet quality. Behavior change was associated with baseline fatigue, diet quality, education, and married/living with someone. Addressing these factors in interventions may improve uptake of lifestyle behaviors in trials during and after chemotherapy.

Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study.

PURPOSE: Use qualitative and quantitative methods to explore factors influencing the adoption of guideline-based physical activity (PA) and dietary recommendations among participants enrolled in a lifestyle intervention during and after chemotherapy for breast cancer. METHODS: Among women with stage I-III breast cancer who participated in the intervention arm of the Lifestyle, Exercise, and Nutrition early after diagnosis (LEANer) trial, we used stratified, purposeful sampling to interview women who met both, one, or neither intervention goal after the 1-year intervention: (1) 150 min/week moderate-to-vigorous intensity exercise via a self-reported PA questionnaire and (2) improved self-reported diet quality measured by the Healthy Eating Index-2015. Semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed using thematic content analysis. RESULTS: The 29 women interviewed were 52 ± 11 years old on average, with a mean body mass index of 29.6 ± 7.7 kg/m2. Three themes emerged regarding aspects of the LEANer intervention that facilitated behavior change: (1) providing a conduit of trustworthy, timely, and personalized support and education; (2) shifting mindsets and enhanced understanding of the benefits of PA and nutrition during chemotherapy; and (3) fostering a sense of control and alternative focus. Factors described as hindering adoption of goals included: (1) adverse effects of chemotherapy and (2) competing priorities. CONCLUSIONS: Women reported the external support, tailored education, and experiencing the physical and mental benefits of the LEANer intervention facilitated the adoption of the interventions' behavioral goals. Addressing chemotherapy-related symptoms and competing priorities may facilitate adherence to lifestyle interventions during chemotherapy for breast cancer.

A qualitative study identifying challenges resulting from complex evidence on lifestyle factors and cancer: perspectives from Black and Latina cancer survivors and healthcare providers.

PURPOSE: Most breast cancer survivors have challenges with adopting healthy lifestyle behaviors. This may be due to contextual challenges that result from the complex nature of the evidence. To address this gap, we explored the experiences of breast cancer survivors of color and oncology healthcare providers. METHODS: Content analysis with inductive and deductive approaches was used for semi-structured interviews with 26 female breast cancer survivors and 10 oncology healthcare providers from Greater New Haven, Connecticut. RESULTS: Survivors identified substantial confusion on the evidence regarding lifestyle behaviors and breast cancer, stemming from inadequate healthcare provider counseling and an overreliance on informal sources of information. Providers identified lack of evidence-based knowledge as a barrier to counseling on these topics. There was a mixed perspective regarding the consistency of evidence, stemming from a combination of gaps in the available evidence and accessing evidence-based knowledge from a wide range of professional resources. Some providers perceived the guidelines as consistent; others felt guidelines were constantly changing, impacting how and on what they counseled. Therefore, many healthcare providers in oncology care relied on generic messaging on lifestyle behaviors after a cancer diagnosis. CONCLUSIONS: Inconsistent information sources, the rapidly changing evidence, and gaps in the current evidence contribute to generic messaging about lifestyle behaviors and may inhibit a survivor's ability to engage in behavior change. Consistent and uniform healthy lifestyle guidelines for cancer outcomes may address both provider and patient level barriers to knowledge.

A competing risk analysis of adherence to the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and obesity-related cancer risk in Hispanic/Latino adults in the NIH-AARP Diet and Health Study.

Incidence of obesity-related cancers (ORCs) is rising among US Hispanic/Latino adults, which may be partly due to inadequate engagement in healthy lifestyle behaviors. Prior research on cancer prevention guideline adherence and cancer risk has not considered competing events that may lead to misinterpreting the magnitude of risk between guideline adherence and cancer incidence. Among Hispanic/Latino adults (N = 9204) in the NIH-AARP Diet and Health Study, we examined the association between adherence to the 2012 American Cancer Society (ACS) guidelines (high, moderate, low) on nutrition and physical activity for cancer prevention and risk of any first observed ORC using Fine and Gray methods for competing risk analysis. Over a median of 10.5 years of follow-up, there were 619 first ORCs. The cumulative risk of ORC over a 15-year period was not significantly different across ACS guideline adherence categories (high cumulative incidence function [CIF]: 2.2%-5.8%; moderate CIF: 2.2%-6.6%; low CIF: 2.3%-6.7%, PGray's log rank  = .690). In competing risk analysis, high (compared to low) adherence to the ACS guidelines was associated with reduced probability of ORC (subdistribution hazard [SHR]: 0.76, 95% CI: 0.58-0.996, P = .047), with evidence of a linear trend for increasing adherence (Ptrend  = .039). Our findings were consistent with hypothesized inverse associations between ACS guideline adherence and ORC incidence accounting for competing risks. These findings suggest a need for continued public health efforts focused on promoting engagement in healthy lifestyle behaviors to reduce ORC incidence among US Hispanic/Latino adults.

Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants.

BACKGROUND: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI). METHODS: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking. RESULTS: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification. CONCLUSIONS: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality. LAY SUMMARY: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.

Examining the effect of obesity-associated gene variants on breast cancer survivors in a randomized weight loss intervention.

PURPOSE: Our study examined whether common variants of obesity-associated genes FTO, MC4R, BDNF, and CREB1 moderated the effects of a lifestyle intervention on weight change among breast cancer survivors. METHODS: 151 breast cancer survivors with a body mass index ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention or usual care group. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed. Linear mixed models were used including the main effects of genotype (assuming a dominant genetic model), treatment arm on weight and percent body fat changes, and genotype by treatment interaction variable. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. RESULTS: Women in the intervention group achieved significantly greater weight loss than the usual care group (5.9% vs 0.4%, p < 0.001), regardless of genotype. Changes in weight and percent body fat did not differ significantly between carriers of the FTO rs9939609, MC4R rs6567160, BDNF rs11030104, and CREB1 rs17203016 risk alleles compared to non-carriers (p-interaction > 0.0125 for each single-nucleotide polymorphisms). CONCLUSIONS: Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may achieve significant and clinically meaningful weight loss through healthy eating and exercise. CLINICAL TRIAL REGISTRATION: NCT02863887 (Date of Registration: August 11, 2016); NCT02110641 (Date of Registration: April 10, 2014).

Endocrine-related quality of life in a randomized trial of exercise on aromatase inhibitor-induced arthralgias in breast cancer survivors.

BACKGROUND: The objective of this study was to evaluate the role of a 12-month exercise intervention on endocrine-related quality of life (QOL) and overall QOL among breast cancer survivors with aromatase inhibitor (AI)-induced arthralgia in the Hormones and Physical Exercise (HOPE) Study. METHODS: This was a randomized controlled trial of 121 breast cancer survivors who were currently receiving AIs and experiencing at least mild arthralgia. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaires and the 36-Item Short Form Survey (SF-36) at baseline, 6 months, and 12 months. Participants were randomized to either a 1-year gym-based, supervised exercise intervention group (150 minutes of aerobic exercise and 2 strength-training sessions each week) or a usual care group. Effects of the intervention on QOL were assessed using mixed-model, repeated-measures analysis. RESULTS: At 12 months, the exercise group had greater improvement in the overall QOL measures as well as the breast cancer-specific (scores, 2.2 vs 0.7; P = .02), endocrine-specific (scores, 5.6 vs 1.6; P < .001), and fatigue-specific (score, 5.8 vs 0.5; P < .001) subscales compared with the usual care group. The results indicated a stronger effect at 12 months versus 6 months after the intervention. CONCLUSIONS: Combined aerobic and resistance exercise, such as treadmill walking and strength training, improved endocrine-related and overall QOL among breast cancer survivors who were experiencing adverse side effects from AIs. Because adverse side effects associated with AI use are quite common and this is the main reason for treatment discontinuation, this nonpharmacologic intervention could benefit many breast cancer survivors and increase successful adherence to AIs in breast cancer treatment.

Concordance of cancer registry and self-reported race, ethnicity, and cancer type: a report from the American Cancer Society's studies of cancer survivors.

PURPOSE: To examine the concordance between cancer registry and self-reported data for race, Hispanic ethnicity, and cancer type in the American Cancer Society's Studies of Cancer Survivors (SCS) I and II. METHODS: We calculated sensitivity, specificity, positive predictive value, and Kappa statistics for SCS-I and II. The gold standard for cancer type was registry data and for race and ethnicity was self-reported questionnaire data. RESULTS: Among 6,306 survivors in SCS-I and 9,170 in SCS-II, overall agreement (Kappa) for cancer type was 0.98 and 0.99, respectively. Concordance was strongest for breast and prostate cancer (Sensitivity ≥ 0.98 in SCS-I and II). For race, Kappa was 0.85 (SCS-I) and 0.93 (SCS-II), with strong concordance for white (Sensitivity = 0.95 in SCS-I and 0.99 in SCS-II) and black survivors (Sensitivity = 0.94 in SCS-I and 0.99 in SCS-II), but weak concordance for American Indian/Alaska Native (Sensitivity = 0.23 in SCS-I and 0.19 in SCS-II) and Asian/Pacific Islander survivors (Sensitivity = 0.43 in SCS-I and 0.87 in SCS-II). Agreement was moderate for Hispanic ethnicity (Kappa = 0.73 and 0.71; Sensitivity = 0.74 and 0.76, in SCS-I and SCS-II, respectively). CONCLUSIONS: We observed strong concordance between cancer registry data and self-report for cancer type in this national sample. For race and ethnicity, however, concordance varied significantly, with the poorest concordances observed for American Indian/Alaska Native and Asian/Pacific Islander survivors. Ensuring accurate recording of race/ethnicity data in registries is crucial for monitoring cancer trends and addressing cancer disparities among cancer survivors.

Randomized controlled trial of weight loss versus usual care on telomere length in women with breast cancer: the lifestyle, exercise, and nutrition (LEAN) study.

PURPOSE: Some studies suggest that telomere shortening may be associated with increased breast cancer risk and mortality. Obesity is also associated with increased breast cancer risk and mortality. Few studies have examined changes in telomere length in overweight or obese breast cancer survivors. The purpose of our study was to examine the effect of a 6-month diet- and exercise-induced weight loss intervention versus usual care on telomere length in breast cancer survivors. METHODS: 151 breast cancer survivors with body mass index (BMI) ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention (n = 93) or to usual care (n = 58). Fasting blood samples, height, weight, physical activity, and diet were measured at baseline and 6-months. Relative telomere length (RTL) was measured by quantitative-polymerase chain reaction (qPCR) done on buffy coat-extracted genomic DNA. Mean baseline to 6-month changes were compared between groups (intention-to-treat) using generalized estimating equations. RESULTS: Complete telomere data were available in 125 participants. Women were 58 ± 8 years, with BMI 33.0 ± 6.2 kg/m2 and were 2.9 ± 2.5 years from diagnosis; 90% were non-Hispanic white, and 76% had stage 0/I breast cancer. After 6 months, women randomized to weight loss had 3% telomere lengthening compared to 5% shortening in the usual care group (p = 0.12). Among women with stage 0/I, the intervention group experienced 7% telomere lengthening compared to 8% shortening in the usual care group (p = 0.01). No intervention effect was observed in women with stage II/III breast cancer. CONCLUSION: Our findings suggest a weight loss intervention in stage 0 and 1 breast cancer survivors may lead to telomere lengthening, compared to a shortening in their usual care counterparts.

Pre-diagnosis diet and survival after a diagnosis of ovarian cancer.

BACKGROUND: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. METHODS: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake. RESULTS: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53-0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62-0.99), fish (HR=0.74, 95% CI: 0.57-0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59-0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01-1.65, P-trend=0.03). CONCLUSIONS: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

Health-related quality of life in ovarian cancer survivors: Results from the American Cancer Society's Study of Cancer Survivors - I.

OBJECTIVE: There are limited data on outcomes and predictors of health-related quality of life (HRQOL) of ovarian cancer survivors. Therefore, we examined the trajectory and predictors of HRQOL one- and two-years post-diagnosis in this population. METHODS: 365 ovarian cancer survivors, a subset of participants in the longitudinal American Cancer Society's Study of Cancer Survivors-I, completed questionnaires at one-year post-diagnosis on sociodemographics, clinical factors, and HRQOL (SF-36). 284 women had HRQOL data at two-years post-diagnosis. In this secondary data analysis, we examined HRQOL at both time points, changes in HRQOL and predictors of HRQOL with univariate and multivariate linear regression. RESULTS: Mean mental and physical HRQOL scores one-year post-diagnosis were 49.37 (SD±11.59) and 45.96 (SD±10.89), respectively. Older age, lower income, higher disease stage, more comorbidities and greater symptom burden were associated with poorer physical functioning one year post-diagnosis. Younger age, higher stage, having an existing mental health issue, greater symptom burden, and not receiving chemotherapy were associated with poorer mental functioning. Disease recurrence between one- and two-years post-diagnosis and greater symptom burden were predictors of declining physical functioning from one- to two-years post-diagnosis. Mental functioning did not change significantly between assessments. CONCLUSIONS: Overall mental and physical functioning of these ovarian cancer survivors was similar to the general population. However, lower HRQOL was associated with a number of variables, including disease recurrence, treatment status, symptom burden, age, and number of comorbidities. These findings can help health care providers identify survivors who may benefit from relevant interventions.

Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort.

Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer.

Dietary iron intake and variation in iron homeostasis genes may affect colorectal neoplasia risk. We conducted two nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: one of advanced colorectal adenoma (1205 cases; 1387 controls) and one of colorectal cancer (370 cases; 401 controls). Iron intake was estimated with a food frequency questionnaire and genotyping was performed for 21 genes. Unconditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) for colorectal neoplasia risk within quartiles of intake. Several single nucleotide polymorphisms (SNPs) modified the association between iron intake and the risk of adenoma or cancer. Dietary iron was positively associated with colorectal adenoma among three SNPs of HEPHL1, including carriers of the AA genotype at rs7946162 (ORQ4-Q1 = 2.22, 95% CI 1.15-4.27, Ptrend = 0.03; Pinteraction = 0.10), the TT genotype at rs2460063 (ORQ4-Q1 = 2.39, 95% CI 1.26-4.54, Ptrend = 0.02; Pinteraction = 0.04) and the GG genotype at rs7127348 (ORQ4-Q1 = 2.40, 95% CI 1.23-4.67, Ptrend = 0.02; Pinteraction = 0.09). Heme iron was positively associated with colorectal cancer among those with GG genotypes for ACO1 rs10970985 (ORQ4-Q 1 = 2.45, 95% CI 3.40-8.06, Ptrend = 0.004; Pinteraction = 0.05). However, none of the associations were statistically significant after adjustment for multiple comparisons. Future studies should target the specific genes and SNPs for which the association was significant prior to multiple comparison correction.

Novel gene identified in an exome-wide association study of tanning dependence.

Growing evidence suggests that some individuals may exhibit symptoms of dependence to ultraviolet light, a known carcinogen, in the context of tanning. Genetic associations with tanning dependence (TD) have not yet been explored. We conducted an exome-wide association study in 79 individuals who exhibited symptoms of TD and 213 individuals with volitional exposure to ultraviolet light, but who were not TD based on three TD scales. A total of 300 000 mostly exomic single nucleotide polymorphisms primarily in coding regions were assessed using an Affymetrix Axiom array. We performed a gene burden test with Bonferroni correction for the number of genes examined (P < 0.05/14 904 = 3.36 × 10(-6) ). One gene, patched domain containing 2 (PTCHD2), yielded a statistically significant P-value of 2.5 × 10(-6) (OR = 0.27) with fewer individuals classified as TD having a minor allele at this locus. These results require replication, but are the first to support a specific genetic association with TD.

Indoor tanning in businesses and homes and risk of melanoma and nonmelanoma skin cancer in 2 US case-control studies.

BACKGROUND: Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based). OBJECTIVE: We sought to assess where individuals tanned indoors and skin cancer risk by tanning device location. METHODS: Multivariate logistic regression was conducted in 2 US case-control studies of melanoma (1161 cases, 1083 controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382 controls, age<40 years) conducted between 2004 and 2010. RESULTS: Most indoor tanners (86.4%-95.1%), especially younger individuals, tanned exclusively in businesses. Persons who used indoor tanning exclusively in businesses were at increased risk of melanoma (odds ratio 1.82, 95% confidence interval 1.47-2.26) and basal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48) compared with non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95% confidence interval 1.75-9.78); 67.6% used sun lamps. LIMITATIONS: Self-reported tanning and potential recall bias are limitations. CONCLUSION: Business-only tanning, despite claims of "safe" tanning, was positively associated with a significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon and mostly from sun lamps, which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer.

Association between diet quality and ovarian cancer risk and survival.

BACKGROUND: Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort. METHODS: We used data from women in the prospective National Institutes of Health-AARP Diet and Health Study enrolled from 1995 to 1996 who were aged 50-71 years at baseline with follow-up through December 31, 2017. Participants completed a 124-item food frequency questionnaire at baseline, and diet quality was assessed via the Healthy Eating Index-2015, the alternate Mediterranean diet score, and the Dietary Approaches to Stop Hypertension score. Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multistate model with Cox proportional hazards regression to account for semicompeting events. RESULTS: Among 150 643 participants with a median follow-up time of 20.5 years, 1107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better prediagnosis diet quality, according to the Healthy Eating Index-2015 (quintile 5 vs quintile 1: hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.60 to 0.93) and alternate Mediterranean diet score (quintile 5 vs quintile 1: HR = 0.68, 95% CI = 0.53 to 0.87), was associated with lower all-cause mortality. There was no evidence of an association between Dietary Approaches to Stop Hypertension score and all-cause mortality. CONCLUSIONS: Better prediagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis but was not associated with ovarian cancer risk.

United States Long-Term Trends in Adult BMI (1959-2018): Unraveling the Roots of the Obesity Epidemic.

The escalating rates of obesity since the 1950s poses a critical public health challenge across all age groups in the United States. While numerous studies have examined cross-sectional disparities across racial, ethnic, and socioeconomic groups, there has been limited research on long-term trends. To address this gap, we analyzed average adult body mass index (BMI) trends from 1959 to 2018, using data from the National Health and Nutrition Examination Survey (NHANES) and the National Health Examination Survey (NHES). Employing time series analysis, we evaluated BMI trends across income, education, and race/ethnicity. The results revealed a consistent upward trajectory in average BMI across all groups over the six-decade period, with no significant differences by income or education levels among high school graduates. However, individuals with less than a high school education displayed a more gradual increase in BMI. Racial disparities were also evident, with Black adults showing higher BMI growth rates compared to White adults, while Hispanic and other racial groups experienced slower increases. These findings underscore the need for systemic interventions to address the ongoing obesity epidemic, emphasizing the importance of research to identify trends over time and a system-thinking approach to inform effective population-level interventions and policy decisions.

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin.

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4×10 -9 per nt, we report that sun exposure creates pervasive mutations at sites with ∼100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3×10 -5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

Exercise and nutrition to improve cancer Treatment-Related outcomes (ENICTO).

Chemotherapy treatment-related side-effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity (RDI). The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium, to address this knowledge gap. This paper describes the mechanisms hypothesized to underpin intervention effects on clinically-relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the paper includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that cancer patients could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve RDI for a curative outcome.