Background : Converging lines of research suggest that activation of the insulin/insulin-like-growth-factor axis may impact prognosis among breast cancer survivors. Carbohydrate intake can stimulate the insulin/insulin-like -growth-factor axis by elevating blood glucose concentrations, and insulin-like-growth-factor-1 receptor (IGF-1R) activation in breast cancers triggers proliferative signaling. This dissertation examined the influence of carbohydrate intake on breast cancer recurrence and all-cause mortality among postmenopausal breast cancer survivors, and whether the odds of recurrence was modified by IGF-1R expression in the primary cancer. Methods : Secondary analysis of N=2,111 postmenopausal breast cancer survivors enrolled in a dietary intervention trial. Baseline and one-year dietary intake was assessed using 24-hour dietary recalls. One- year change in carbohydrate intake was quantified as tertiles (grams/day) and change in approximately one serving of high or low quality carbohydrate-based foods; quality considered the impact on blood glucose concentrations. Samples of primary breast cancer tissue (N=265) were stained in a nested, case-control, immunohistochemical study to test the interaction between a decreased carbohydrate intake and IGF-1R expression on odds of recurrence. Finally, the impact of carbohydrate quality (high vs. low) on outcomes was assessed among the full cohort. Results : Dietary changes began a median 24 months post-diagnosis. Over a median 7 years, there were N=247 (11.7%) recurrences. Risk of recurrence significantly increased over tertiles of change in carbohydrate intake (p=0.055). A decreased carbohydrate intake (< -26 grams/day) reduced the risk of recurrence by 30% (HR: 0.7; 95%CI:0.5-1.0). Risk reduction significantly differed (p=0.110) by IGF-1R expression in the primary breast cancer: a decreased carbohydrate intake reduced the odds of recurrence by 30% (conditional OR: 0.7;95%CI:0.2- 1.7) among participants who had IGF-1R negative cancers and 80% (conditional OR: 0.2;95%CI:0.03-0.3) among participants who had IGF-1R positive cancers. Among the full cohort, only a decreased intake of low quality carbohydrates (e.g., refined grains, sweets, starchy vegetables) was protective, and only among participants who did not decrease their intake of high quality carbohydrates (e.g., fruits, non-starchy vegetables, whole grains, dairy). Conclusions : Results support that modifications in carbohydrate intake may impact prognosis among postmenopausal breast cancer survivors via the insulin/insulin-like-growth-factor axis. Importantly, carbohydrate quality may be more important that quantity relative to prognosis

Background

The insulin-like growth factor-I (IGFI) receptor is a potential target for breast cancer treatment and may be influenced by dietary intake.

Methods

Nested, case-control study of 265 postmenopausal breast cancer survivors; primary breast cancer tissue was stained to determine IGFI receptor status. Change in carbohydrate intake from baseline to year 1 of study was estimated from 24-hour dietary recalls. Breast cancer recurrence cases (91) were matched to two controls (n = 174) on disease and study characteristics and counter matched on change in carbohydrate intake. Weighted conditional logistic regression models fit the risk of recurrence on IGFI receptor status and dietary change.

Results

Half of the tumors were IGFI receptor positive. Increased risk of recurrence was associated with IGFI receptor-positive status [HR 1.7; 95% confidence interval (CI), 1.2-2.5] and, separately, with a stable/increased intake of carbohydrates (HR 2.0; 95% CI, 1.3-5.0). There was a borderline significant interaction between those two variables (P = 0.11). Specifically, carbohydrate intake had no significant impact on risk of recurrence among women who were receptor negative, yet increased the risk of recurrence by more than 5-fold among women who were receptor positive (HR 5.5; 95% CI, 1.8-16.3).

Conclusions

Among women whose tumor tissue is positive for the IGFI receptor, reducing carbohydrate intake after diagnosis could reduce the risk of breast cancer recurrence. These findings need replication in a larger sample.

Impact

This is the first study to suggest that it may be possible to personalize dietary recommendations for breast cancer survivors based on molecular characteristics of their primary tumor tissue. .

Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity.

Introduction

We examined the relationship between current tobacco use and functionally important respiratory symptoms.

Methods

Longitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders.

Results

All tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]).

Conclusions

Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity.

Implications

How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

Introduction

Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions.

Objectives

The aim of this study was to examine the strength and shape of the relationship between adults' neighborhood perceptions and walking and cycling for transport across diverse environments.

Methods

As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18-65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire-Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored.

Results

Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix-access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix-access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport.

Conclusions

Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies.