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1.  Red Meat Consumption during Adolescence among Premenopausal Women and Risk of Breast Cancer 
Background
Adolescence may be a period of increased susceptibility to breast cancer due to regular division of undifferentiated cells that occurs between puberty and first birth. Red meat consumption during early adult life has been associated with breast cancer, but intake during adolescence has not been examined prospectively. We aimed to assess the relationship between various types of red meat intake during adolescence and premenopausal breast cancer. Methods: We examined the incidence of invasive pre-menopausal breast cancer prospectively within the Nurses’ Health Study II. A total of 39,268 premenopausal women who completed a validated 124-item food frequency questionnaire on their diet during high school, were followed for 7 years, from 1998 to 2005. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI).
Results
455 cases of invasive premenopausal breast cancer were diagnosed between 1998 and 2005. Compared with women in the lowest quintile of red meat intake during high school, the multivariate-adjusted RR for the highest quintile of intake was 1.34 (95% CI, 0.94–1.89; Ptrend = 0.05). A significant linear association was observed with every additional 100 g of red meat consumed per day (RR, 1.20; 95% CI, 1.00–1.43; P = 0.05). This association was more pronounced in hormone receptor–positive tumors (RR, 1.36; 95% CI, 1.08–1.70; P = 0.008) and was not significant in hormone receptor negative tumors (RR, 0.99; 95% CI, 0.61–1.61, P = 0.97). Our conclusions: Higher red meat intake in adolescence may increase the risk of premenopausal breast cancer.
doi:10.1158/1055-9965.EPI-08-0037
PMCID: PMC4510942  PMID: 18669582
3.  Use of Aspirin, Other Nonsteroidal Anti-Inflammatory Drugs, and Acetaminophen and Postmenopausal Breast Cancer Incidence 
Journal of Clinical Oncology  2012;30(28):3468-3477.
Purpose
The associations between use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen and breast cancer incidence in postmenopausal women are uncertain. We examined these associations with breast cancer, both overall and by molecular subtype.
Patients and Methods
We observed 84,602 postmenopausal women, free of cancer in 1980, until June 2008 and prospectively collected data on analgesic use, reproductive history, and other lifestyle factors using biennial questionnaires. Proportional hazards models were used to estimate multivariable relative risks (RRs) and 95% CIs.
Results
We documented 4,734 cases of incident invasive breast cancer. Compared with nonuse of aspirin, multivariable RRs of regular aspirin use (≥ two tablets per week) for more than 20 years were 0.91 for overall breast cancer (95% CI, 0.81 to 1.01; Ptrend = 0.16), 0.90 for estrogen receptor (ER) –positive progesterone receptor (PR) –positive breast cancer (95% CI, 0.77 to 1.06; Ptrend = 0.17), and 0.91 for ER-negative PR-negative breast cancer (95% CI, 0.68 to 1.22; Ptrend = 0.97). Results did not vary appreciably by past or current use, days per week of use, or dosage of use. Use of other NSAIDs and acetaminophen was largely not significantly associated with breast cancer risk. Additionally, use of higher doses of each analgesic (≥ six tablets per week) for more than 10 years was generally not significantly associated with risk of breast cancer, either overall or by subtype. Furthermore, largely no substantial associations were noted for breast cancer molecular subtypes, including luminal A, luminal B, triple negative, basal-like, human epidermal growth factor receptor 2 positive, cyclooxygenase-2 (COX-2) negative, and COX-2 positive.
Conclusion
Our study suggests that use of aspirin, other NSAIDs, and acetaminophen is not importantly associated with risk of postmenopausal breast cancer, either overall or by specific subtype.
doi:10.1200/JCO.2012.42.2006
PMCID: PMC3454769  PMID: 22927520
4.  Dietary patterns and plasma sex hormones, prolactin and sex hormone-binding globulin in premenopausal women 
Background
Sex hormones are important for breast cancer but it is unclear whether dietary patterns influence hormone concentrations.
Methods
Dietary pattern adherence scores for the alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Alternative Healthy Eating Index (AHEI) were calculated from semiquantitative food frequency questionnaires administered in 1995 and 1999. Premenopausal plasma concentrations of sex hormones were measured in samples collected in 1996–1999. We used generalized linear models to calculate geometric mean hormone concentrations across quartiles of dietary pattern scores among 1,990 women in the Nurses’ Health Study II.
Results
We did not observe significant associations between sex hormone concentrations and the DASH pattern, and only one suggestive association between follicular estrone concentrations and the aMED pattern (top vs. bottom quartile −4.4%, (95%CI −10.6%, 2.1%), p-trend=0.06). However, women in the top vs. bottom quartile of AHEI score had lower concentrations of follicular (−9.1%, 95%CI: −16.1%, −1.4%; p-trend=0.04) and luteal (−7.5%, 95%CI: −13.6%, −0.9%; p-trend=0.01) estrone, luteal free (−9.3%, 95%CI: −16.8%, −1.1%; p-trend=0.01), and total (−6.7 %, 95%CI: −14.3%, 1.5%; p-trend=0.04) estradiol, follicular estradiol (−14.2 %, 95%CI: −24.6%, −2.4%; p-trend=0.05) and androstenedione (−7.8%, 95%CI: −15.4%, 0.4%; p-trend=0.03).
Conclusion
Diet quality measured by the AHEI is inversely associated with premenopausal estrogen concentrations. Given we did not observe similar associations with the aMED or DASH patterns, our findings should be interpreted with caution.
Impact
Given the role of estrogens in breast cancer etiology, our findings add to the substantial evidence on the benefits of adhering to a healthy diet.
doi:10.1158/1055-9965.EPI-15-1019
PMCID: PMC5082703  PMID: 26980437
Dietary patterns; sex hormones; premenopausal
5.  Early life body fatness and risk of colorectal cancer in US women and men – results from two large cohort studies 
Background
The association between body fatness before adulthood and later risk of colorectal cancer remains unclear. We hypothesized that, independent of adult body fatness, early life body fatness would be associated with a higher risk of developing colorectal cancer.
Methods
We assessed body fatness during childhood and adolescence using a validated 9-level somatotype and inquired body weight in young adulthood in the Nurses' Health Study and Health Professionals Follow-up Study. We used Cox proportional hazard regression modeling to estimate relative risks (RRs, 95% CIs) adjusting for adult body mass index (BMI) and other known colorectal cancer risk factors.
Results
We identified 2,100 incident colorectal cancer cases (1,292 in women and 808 in men) during 22 years of follow-up. Among women, the RR(95% CI) for childhood body fatness of level 5 or higher versus level 1 was 1.28(1.04-1.58, p-trend=0.08) and for adolescent body fatness, it was 1.27(1.01-1.60, p-trend = 0.23). The corresponding RRs for men were 1.04(0.82-1.31, p-trend=0.48) and 0.98(0.75-1.27, p-trend=0.20), respectively. Results were generally similar across anatomic subsites within the colorectum. Additionally, the RRs comparing BMI categories ≥ 27.5 to < 19 kg/m2 were 1.44(1.06-1.95, at age 18, p-trend=0.009) for women and 1.18(0.84-1.65, at age 21, p-trend=0.57) for men.
Conclusion
Increased body fatness in early life, independent of adult obesity, might be a risk factor for colorectal cancer in women, but we observed a weaker association in men.
Impact
Our findings support the growing evidence that early life body fatness affects the risk of colorectal cancer many decades later.
doi:10.1158/1055-9965.EPI-14-0909-T
PMCID: PMC4412364  PMID: 25777804
body fatness; early life; childhood; adolescence; colorectal cancer
6.  Inclusion of Endogenous Hormone Levels in Risk Prediction Models of Postmenopausal Breast Cancer 
Journal of Clinical Oncology  2014;32(28):3111-3117.
Purpose
Endogenous hormones are risk factors for postmenopausal breast cancer, and their measurement may improve our ability to identify high-risk women. Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone–binding globulin (SHBG) improved risk prediction for postmenopausal invasive breast cancer (n = 437 patient cases and n = 775 controls not using postmenopausal hormones) in the Nurses' Health Study.
Methods
We evaluated improvement in the area under the curve (AUC) for 5-year risk of invasive breast cancer by adding each hormone to the Gail and Rosner-Colditz risk scores. We used stepwise regression to identify the subset of hormones most associated with risk and assessed AUC improvement; we used 10-fold cross validation to assess model overfitting.
Results
Each hormone was associated with breast cancer risk (odds ratio doubling, 0.82 [SHBG] to 1.37 [estrone sulfate]). Individual hormones improved the AUC by 1.3 to 5.2 units relative to the Gail score and 0.3 to 2.9 for the Rosner-Colditz score. Estrone sulfate, testosterone, and prolactin were selected by stepwise regression and increased the AUC by 5.9 units (P = .003) for the Gail score and 3.4 (P = .04) for the Rosner-Colditz score. In cross validation, the average AUC change across the validation data sets was 6.0 (P = .002) and 3.0 units (P = .03), respectively. Similar results were observed for estrogen receptor–positive disease (selected hormones: estrone sulfate, testosterone, prolactin, and SHBG; change in AUC, 8.8 [P < .001] for Gail score and 5.8 [P = .004] for Rosner-Colditz score).
Conclusion
Our results support that endogenous hormones improve risk prediction for invasive breast cancer and could help identify women who may benefit from chemoprevention or more screening.
doi:10.1200/JCO.2014.56.1068
PMCID: PMC4171356  PMID: 25135988
7.  Citrus Consumption and Risk of Cutaneous Malignant Melanoma 
Journal of Clinical Oncology  2015;33(23):2500-2508.
Purpose
Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption.
Methods
A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records.
Results
Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001).
Conclusion
Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications.
doi:10.1200/JCO.2014.57.4111
PMCID: PMC4979231  PMID: 26124488
8.  PARENTAL SMOKING IN PREGNANCY AND THE RISKS OF ADULT ONSET HYPERTENSION 
Hypertension  2012;61(2):494-500.
Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33,086 participants of the Nurses’ Health Study II and the Nurses’ Mothers’ Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8,575 (25.9%) mothers and 18,874 (57.0%) fathers smoked during pregnancy. During follow-up, 7,825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥15 cigarettes/day during pregnancy were associated with increased risks of hypertension (RR 1.19, 95% CI 1.09 to 1.29, and RR 1.18, 95% CI 1.12 to 1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, while additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (RR 1.07, 95% CI 0.98 to 1.16, and RR 1.06, 95% CI 1.01 to 1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.
doi:10.1161/HYPERTENSIONAHA.111.200907
PMCID: PMC3606889  PMID: 23266542
Pregnancy; parental smoking; hypertension; body mass index
10.  Physical Activity and the Risk of Community-Acquired Pneumonia in US Women 
The American journal of medicine  2010;123(3):281.e7-281.e11.
Background
Exercise bolsters the immune system, and can prevent various infections in certain populations. However, limited data exist regarding the role of physical activity and the risk of community-acquired pneumonia.
Methods
We prospectively examined, during a 12-year period, the association between physical activity and the risk of community-acquired pneumonia among 83,165 women in Nurses’ Health Study (NHS) II who were between the ages of 27 and 44 years in 1991.We excluded women who had pneumonia prior to 1991, and those with a history of cancer, cardiovascular disease or asthma. Biennial self-administered mailed questionnaires were used to determine activity level. Cases of pneumonia required a diagnosis by a physician and confirmation with a chest radiograph.
Results
We identified 1265 new cases of community-acquired pneumonia during 965,168 person-years of follow up. After adjusting for age, women in the highest quintile of physical activity were less likely to develop pneumonia than women in the lowest quintile (relative risk [RR] =0.72; 95% confidence interval [CI], 0.60–0.86; p for trend < 0.001). However, the association was attenuated and only marginally significant after further adjusting for body-mass index (BMI), smoking and alcohol use (RR=0.84; 95% CI, 0.70–1.01; p for trend=0.06). Women in the highest quintile of walking were less likely to develop pneumonia compared to women who walked the least (multivariate adjusted RR=0.82; 95% CI, 0.69–0.98); however, the trend across quintiles was not significant (p for trend=0.25).
Conclusions
Higher physical activity does not substantially reduce pneumonia risk in well-nourished women.
doi:10.1016/j.amjmed.2009.07.028
PMCID: PMC2847455  PMID: 20193839
11.  Consumption of cured meats and prospective risk of chronic obstructive pulmonary disease in women123 
Background
Most cured meats contain nitrites. Nitrites generate oxidative-nitrative stress and were shown in animal models to cause emphysema. Prospective epidemiologic data on cured meats and chronic obstructive pulmonary disease (COPD), however, are sparse.
Objective
We examined the relation between cured meat consumption and the prospective risk of newly diagnosed COPD in women.
Design
This was a prospective cohort study of 71 531 women from the Nurses’ Health Study who completed a validated dietary questionnaire at baseline in 1984 and had no baseline COPD or a report of asthma. Participants were aged 38–63 y in 1984 and were followed for 16 y.
Results
A total of 750 new cases of COPD were documented during the follow-up. Cured meat consumption was positively associated with COPD risk after adjustment for age, smoking, and multiple other potential confounders. The adjusted relative risks of COPD across categories of cured meat consumption (never or almost never, 1–3 servings/mo, 1 serving/wk, 2–3 servings/wk, and ≥4 servings/wk) were 1.0, 1.14 (95% CI: 0.78, 1.66), 1.15 (95% CI: 0.79, 1.69), 1.40 (95% CI: 0.96, 2.05), and 1.51 (95% CI: 1.00, 2.27), respectively, (P for trend = 0.005). This positive association was present among both past (P for trend = 0.02) and current (P for trend = 0.03) smokers. No association was observed among never smokers, probably because of the small number of COPD cases in these women.
Conclusion
Frequent cured meat consumption was associated with an increased risk of newly diagnosed COPD among women who smoke.
PMCID: PMC2665788  PMID: 18400725
12.  Additive Interactions Between Susceptibility Single-Nucleotide Polymorphisms Identified in Genome-Wide Association Studies and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium 
Joshi, Amit D. | Lindström, Sara | Hüsing, Anika | Barrdahl, Myrto | VanderWeele, Tyler J. | Campa, Daniele | Canzian, Federico | Gaudet, Mia M. | Figueroa, Jonine D. | Baglietto, Laura | Berg, Christine D. | Buring, Julie E. | Chanock, Stephen J. | Chirlaque, María-Dolores | Diver, W. Ryan | Dossus, Laure | Giles, Graham G. | Haiman, Christopher A. | Hankinson, Susan E. | Henderson, Brian E. | Hoover, Robert N. | Hunter, David J. | Isaacs, Claudine | Kaaks, Rudolf | Kolonel, Laurence N. | Krogh, Vittorio | Le Marchand, Loic | Lee, I-Min | Lund, Eiliv | McCarty, Catherine A. | Overvad, Kim | Peeters, Petra H. | Riboli, Elio | Schumacher, Fredrick | Severi, Gianluca | Stram, Daniel O. | Sund, Malin | Thun, Michael J. | Travis, Ruth C. | Trichopoulos, Dimitrios | Willett, Walter C. | Zhang, Shumin | Ziegler, Regina G. | Kraft, Peter | Joshi, Amit D. | Lindström, Sara | Hunter, David J. | Kraft, Peter | Hüsing, Anika | Barrdahl, Myrto | Kaaks, Rudolf | Kraft, Peter | VanderWeele, Tyler J. | Trichopoulos, Dimitrios | Campa, Daniele | VanderWeele, Tyler J. | Campa, Daniele | Canzian, Federico | Gaudet, Mia M. | Figueroa, Jonine D. | Chanock, Stephen J. | Hoover, Robert N. | Ziegler, Regina G. | Baglietto, Laura | Giles, Graham G. | Severi, Gianluca | Baglietto, Laura | Giles, Graham G. | Severi, Gianluca | Berg, Christine D. | Buring, Julie E. | Lee, I-Min | Zhang, Shumin | Chirlaque, María-Dolores | Chirlaque, María-Dolores | Diver, W. Ryan | Thun, Michael J. | Dossus, Laure | Dossus, Laure | Giles, Graham G. | Haiman, Christopher A. | Schumacher, Fredrick | Stram, Daniel O. | Henderson, Brian E. | Hankinson, Susan E. | Isaacs, Claudine | Kolonel, Laurence N. | Krogh, Vittorio | Marchand, Loic Le | Lund, Eiliv | McCarty, Catherine A. | Overvad, Kim | Peeters, Petra H. | Peeters, Petra H. | Riboli, Elio | Sund, Malin | Travis, Ruth C. | Trichopoulos, Dimitrios | Trichopoulos, Dimitrios | Willett, Walter C.
American Journal of Epidemiology  2014;180(10):1018-1027.
Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10−5) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)2). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
doi:10.1093/aje/kwu214
PMCID: PMC4224360  PMID: 25255808
additive interactions; breast cancer; genome-wide association studies; single-nucleotide polymorphisms
13.  Does a grill menu redesign influence sales, nutrients purchased, and consumer acceptance in a worksite cafeteria? 
Preventive Medicine Reports  2017;8:140-147.
Worksite cafeterias are compelling venues to improve diet quality through environmental changes.
We conducted a pre-post study to evaluate how a cafeteria-initiated grill menu redesign influenced sales, revenue, and nutrient content of foods purchased. Secondly, we evaluated consumer opinions about menu changes to inform practices for worksite environment interventions. Monthly sales data (2012–2015) were used to compute gross sales and revenue of entrées and side dishes pre-post menu changes. Alternative protein sources replaced red meat; nutrient composition and nutrients purchased were compared using Food Pro software. Consumer responses were queried using online surveys; open-ended responses were analyzed using NVivo. Differences in sales and nutrient content pre-post menu redesign were tested with Wilcoxon Rank Sum tests. Gross sales of entrées (61 vs. 222 servings/month; p = 0.01) and side dishes (120 vs. 365 servings/month; p = 0.001) increased more than three-fold post-menu changes. Revenue from entrées (312 vs. 1144 USD/month; p = 0.01) and side dishes (238 vs. 914 USD/month; p = 0.001) also increased; per entrée, consumers purchased significantly more unsaturated fat (5 g), and less saturated fat (3 g) and sodium (100 mg). For side dishes, they purchased fewer calories (48 kcal) and unsaturated fat (2.9 g), but more fiber (1.8 g), and sodium (260 mg). Four themes emerged from consumer responses: the importance of 1) variety, novelty, choice; 2) cost, affordability, value; 3) health; and 4) food quality, taste. Menu redesign can improve nutrient content, while also increasing sales and revenue. Multi-dimensional assessment of the nutritional, consumer, and retailer implications is desirable practice for enacting similar environmental changes.
Highlights
•Redesigning menus may improve nutrient content and promote sales.•Consumers value variety even when well-liked offerings are available.•Sodium use requires scrutiny when redesigning menu items.
doi:10.1016/j.pmedr.2017.09.001
PMCID: PMC5635243
Worksite health promotion; Food environment change; Consumer satisfaction; Menu redesign; Sales and revenue
14.  FRUIT AND VEGETABLE CONSUMPTION AND THE INCIDENCE OF HYPERTENSION IN THREE PROSPECTIVE COHORT STUDIES 
Increased fruit and vegetable intake lowers blood pressure in short-term interventional studies. However, data on the association of long-term intake of fruits and vegetables with hypertension risk are scarce.
We prospectively examined the independent association of whole fruit (excluding juices) and vegetable intake, as well as the change in consumption of whole fruits and vegetables, with incident hypertension in three large longitudinal cohort studies: Nurses’ Health Study (n=62,175), Nurses’ Health Study II (n=88,475), and Health Professionals Follow-up Study (n =36,803). We calculated hazard ratios and 95% confidence intervals for fruit and vegetable consumption while controlling for hypertension risk factors. Compared with participants whose consumption was ≤4servings/week, the pooled hazard ratios among those whose intake was ≥4servings/day were 0.92(0.87–0.97) for total whole fruit intake and 0.95(0.86–1.04) for total vegetable intake. Similarly, compared with participants who did not increase their fruit or vegetable consumption, the pooled hazard ratios for those whose intake increased by ≥7servings/week were 0.94(0.90–0.97) for total whole fruit intake and 0.98(0.94–1.01) for total vegetable. Analyses of individual fruits and vegetables yielded different results. Consumption levels of ≥4servings/per week (as opposed to <1serving/month) of broccoli, carrots, tofu or soybeans, raisins and apples was associated with lower hypertension risk.
In conclusion, our results suggest that greater long-term intake and increased consumption of whole fruits may reduce the risk of developing hypertension.
doi:10.1161/HYPERTENSIONAHA.115.06497
PMCID: PMC5350612  PMID: 26644239
hypertension; incidence; epidemiology; prospective studies; fruit; vegetables
15.  Cigarette Smoking Before and After Breast Cancer Diagnosis: Mortality From Breast Cancer and Smoking-Related Diseases 
Journal of Clinical Oncology  2016;34(12):1315-1322.
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.
doi:10.1200/JCO.2015.63.9328
PMCID: PMC4872346  PMID: 26811527
16.  Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance) 
Journal of Clinical Oncology  2015;33(31):3598-3607.
Purpose
Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown.
Patients and Methods
During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression.
Results
Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality.
Conclusion
Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer.
doi:10.1200/JCO.2015.61.5062
PMCID: PMC4622099  PMID: 26282659
19.  Adiposity and Different Types of Screen Time 
Pediatrics  2013;132(6):e1497-e1505.
OBJECTIVE:
Few prospective studies have examined separate forms of screen time in relation to adiposity. Our objective was to assess independent relations of television, electronic games (video/computer), and digital versatile disc (DVD)/videos and total screen time with change in adolescent BMI.
METHODS:
Using data from the 2004, 2006, and 2008 waves of the ongoing Growing up Today Study II, we assessed baseline and 2-year change in reported screen time in relation to concurrent change in BMI among 4287 girls and 3505 boys aged 9 to 16 years in 2004. Gender-specific models adjusted for previous BMI, age, race/ethnicity, growth/development, months between questionnaires, and physical activity.
RESULTS:
Among girls and boys, each hour per day increase in reported television viewing was associated with a 0.09 increase in BMI (Ps < .001), and each hour per day increase in total screen time was associated with a 0.07 increase among girls and 0.05 increase among boys (Ps < .001). Among girls only, greater baseline television, games, and total screen time and change in DVDs/videos were associated with gains in BMI (Ps < .05). BMI gains associated with change in television and total screen time were stronger among overweight girls than lean girls (Ps-heterogeneity < .001).
CONCLUSIONS:
Television, which remains the steadiest source of food advertising, was most consistently associated with BMI gains. Among girls, electronic games and DVDs/videos were also related to increased BMI, possibly due to influences of product placements and advergames on diet and/or distracted eating. Adolescents, especially overweight adolescents, may benefit from reduced time with multiple types of media.
doi:10.1542/peds.2013-0887
PMCID: PMC3838528  PMID: 24276840
television; video games; sedentary lifestyle; BMI; body weight; adolescent; adiposity; longitudinal studies
20.  The relation of midlife diet to healthy aging: a cohort study 
Annals of internal medicine  2013;159(9):584-591.
Background
Understanding how to maintain health and well-being in aging populations is critical.
Objective
To examine the relation of dietary patterns in midlife to the prevalence of healthy aging.
Design
Cross-sectional observational study.
Setting
Nurses’ Health Study.
Participants
10,670 women with dietary data and no major chronic diseases in 1984–1986, when they were in their late 50’s and early 60s (median age = 59 years); all women provided information on multiple aspects of aging an average 15 years later.
Measurements
Diet quality in midlife was ascertained using the Alternative Healthy Eating Index-2010 (AHEI-2010) and Alternate Mediterranean diet (A-MeDi) scores, averaged from two food frequency questionnaires (1984–1986). We defined “healthy” vs “usual” aging as of age 70 years; healthy aging was based on survival to 70+ years with maintenance of four health domains - no major chronic diseases, or major impairments in cognitive or physical function or mental health.
Results
After multivariable adjustment, greater adherence to the AHEI-2010 (upper vs. lower quintile) in midlife was related to 34% (95% CI=9% to 66%, P-trend<0.001) greater odds of healthy versus usual aging. Greater adherence to A-MeDi was related to 46% (95% CI=17% to 83%, P-trend=0.002) greater odds of healthy aging. When the 4 components of healthy aging were analyzed separately, AHEI-2010 and A-MeDi were significantly associated with higher likelihood of no major limitations in physical function and mental health.
Limitations
Possibility of residual confounding, although we controlled for many confounding factors; bias due to complex patterns of measurement error within diet scores cannot be excluded.
Conclusions
Better diet quality at midlife appears strongly linked to greater health and well-being among those surviving to older ages.
doi:10.7326/0003-4819-159-9-201311050-00004
PMCID: PMC4193807  PMID: 24189593
21.  Alcohol Consumption Before and After Breast Cancer Diagnosis: Associations With Survival From Breast Cancer, Cardiovascular Disease, and Other Causes 
Journal of Clinical Oncology  2013;31(16):1939-1946.
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.
doi:10.1200/JCO.2012.46.5765
PMCID: PMC3661933  PMID: 23569314
22.  Self-administered semiquantitative food frequency questionnaires: patterns, predictors, and interpretation of omitted items 
Epidemiology (Cambridge, Mass.)  2009;20(2):295-301.
Background
Food items on a self-administered food frequency questionnaire (FFQ) may be left blank because the food was not consumed, because of difficulties remembering the frequency or amount of intake, or due to an oversight.
Methods
We explored the predictors and frequency of consumption of omitted food items on an FFQ used in the Nurses’ Health Study II. Of 87,676 women who returned a mailed 147-item FFQ in 1999, 34% completed the entire questionnaire, whereas 66% left at least 1 food item blank. Ten or more foods were omitted by 5% of participants. Foods were more likely omitted by women who were older, more physically active, and had more children. We resurveyed 2876 participants who had left between 1 and 70 food items blank and asked them to fill in the blanks. Overall, 2485 participants provided complete responses.
Results
In the resurvey, 64% of the formerly omitted foods were marked as consumed never or less than once per month, 20% as 1–3 times per month, 8% as once per week, and 9% as more than once per week. Commonly consumed foods and beverages were less likely omitted because they were not consumed than rarely consumed foods. The best estimate for the true intake value of an omitted food was 0.82 times the average population intake.
Conclusions
When calculating nutrient intake, the assumption that items missing represent zero intake is reasonable. However, foods consumed more often in the population at large are less likely than rarely consumed foods to be left blank because they were not consumed.
doi:10.1097/EDE.0b013e3181931515
PMCID: PMC3935217  PMID: 19106799
23.  Walnut Consumption Is Associated with Lower Risk of Type 2 Diabetes in Women12 
The Journal of Nutrition  2013;143(4):512-518.
Walnuts are rich in polyunsaturated fatty acids and have been shown to improve various cardiometabolic risk factors. We aimed to investigate the association between walnut intake and incident type 2 diabetes in 2 large cohort studies: the Nurses’ Health Study (NHS) and NHS II. We prospectively followed 58,063 women aged 52–77 y in NHS (1998–2008) and 79,893 women aged 35–52 y in NHS II (1999–2009) without diabetes, cardiovascular disease, or cancer at baseline. Consumption of walnuts and other nuts was assessed every 4 y using validated food frequency questionnaires. Self-reported type 2 diabetes was confirmed by a validated supplemental questionnaire. We documented a total of 5930 incident type 2 diabetes cases during 10 y of follow-up. In the multivariable-adjusted Cox proportional hazards model without body mass index (BMI), walnut consumption was associated with a lower risk of type 2 diabetes, and the HRs (95% CIs) for participants consuming 1–3 servings/mo (1 serving = 28 g), 1 serving/wk, and ≥2 servings/wk of walnuts were 0.93 (0.88–0.99), 0.81 (0.70–0.94), and 0.67 (0.54–0.82) compared with women who never/rarely consumed walnuts (P-trend < 0.001). Further adjustment for updated BMI slightly attenuated the association and the HRs (95% CIs) were 0.96 (0.90–1.02), 0.87 (0.75–1.01), and 0.76 (0.62–0.94), respectively (P-trend = 0.002). The consumption of total nuts (P-trend < 0.001) and other tree nuts (P-trend = 0.03) was also inversely associated with risk of type 2 diabetes, and the associations were largely explained by BMI. Our results suggest that higher walnut consumption is associated with a significantly lower risk of type 2 diabetes in women.
doi:10.3945/jn.112.172171
PMCID: PMC3738245  PMID: 23427333
24.  Omega-3 Intake and Visual Acuity in Patients with Retinitis Pigmentosa on Vitamin A 
Archives of ophthalmology  2012;130(6):707-711.
Objective
We evaluated whether a diet high in long chain omega-3 fatty acids can slow the rate of visual acuity loss among patients with retinitis pigmentosa on vitamin A palmitate.
Methods
We calculated dietary intake from questionnaires completed annually by 357 adult patients who were all receiving vitamin A 15,000 IU/day for 4–6 years. Rates of visual acuity decline were compared between those with high (≥ 0.20 g/day) versus low (<0.20 g/day) omega-3 intake. Analyses took age into account.
Results
Mean rates of decline of acuity were slower among those with high omega-3 intake; ETDRS distance acuity: high =0.59 letter/year, low=1.00 letter/year, p=0.001; Snellen retinal acuity: high = 1.5%/year; low = 2.8%/year, p=0.030.
Conclusions
We conclude that mean annual rates of decline in distance and retinal visual acuities in adults with retinitis pigmentosa taking vitamin A 15,000 IU/day are slower over 4–6 years among those consuming a diet rich in omega-3 fatty acids. To our knowledge this is the first report that nutritional intake can modify the rate of decline of visual acuity in retinitis pigmentosa.
doi:10.1001/archophthalmol.2011.2580
PMCID: PMC3552384  PMID: 22332205
25.  Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study 
BMJ : British Medical Journal  1998;317(7169):1341-1345.
Objective
To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses’ Health Study.
Design
Prospective cohort study.
Setting
Nurses’ Health Study.
Subjects
86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980.
Main outcome measures
Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease.
Results
1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking, use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits.
Conclusions
Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.
Key messagesNuts are high in fat, but most of the fatty acids are unsaturatedThis study suggests that frequent consumption of nuts, including peanuts, may reduce the risk of coronary heart diseaseThis protective effect may be partly mediated through serum lipids because unsaturated fats have benefical effects on serum lipids. Other potentially protective constituents include vegetable protein, magnesium, vitamin E, fibre, and potassiumNuts can be included as part of a healthy diet
PMCID: PMC28714  PMID: 9812929

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