Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: As one of the 10 most common cancers in the United States, bladder cancer is the most expensive cancer to treat. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed. However, 50% to 80% of NMIBC recurs within 5 years, and 15% to 30% progresses with poor survival. Besides life-long surveillance, current treatment is limited. Preclinical and epidemiologic evidence suggest that dietary isothiocyanates (ITCs) in cruciferous vegetables (Cruciferae) could be a noninvasive and cost-effective strategy to improve NMIBC prognosis. Yet, a Cruciferae intervention that increases ITC exposure in NMIBC survivors has not been tested. Thus, the primary aim of this study was to test the effect of a Cruciferae intervention on urinary ITC levels and Cruciferae intake in NMIBC survivors. PATIENTS AND METHODS: We conducted a 2-arm, double-blinded, randomized controlled trial to test the efficacy of a Cruciferae intervention against a general fruit and vegetable intervention (control) for NMIBC survivors. Both 6-month interventions consisted of mailed educational materials, a live call with staff to review the materials, and 11 interactive voice response calls. We anticipated that our Cruciferae intervention (Power to Redefine Your Health [POW-R Health]) would increase Cruciferae intake to 1 cup/day (secondary outcome), thus raising urinary ITC levels to 10 µM (primary outcome) from baseline to 6-month follow-up. RESULTS: We randomized 49 patients with NMIBC diagnosed in 2018 through 2019, and retained 42 patients at 6-month follow-up. The treatment group reported 0.94 cups (95% CI, 0.24-1.65; P=.010) higher Cruciferae intake (treatment, 1.37 ± 1.19 cups vs control, 0.56 ± 0.72 cups) and increased urinary ITC levels by 11.1 µmol/g creatinine (treatment, 26.2 ± 20.9 vs control, 7.8 ± 11.5; P=.027) at 6-month follow-up compared with the control group. CONCLUSIONS: Our dietary intervention is the first to significantly increase Cruciferae intake and urinary ITC levels in NMIBC survivors, demonstrating an increase in ITC to levels that significantly decrease risk of disease-specific survival. A future randomized controlled trial testing POW-R Health on bladder cancer recurrence and progression is warranted. If proven to improve bladder cancer outcomes, our intervention has the potential to be a noninvasive, cost-effective, easily accessible way for NBMIC survivors to improve their bladder cancer prognosis.

Dietary risk factors for monoclonal gammopathy of undetermined significance in a racially diverse population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma, is associated with shorter lifespan and cardiac, renal, neurologic, and immune-related comorbidities. There is little known about modifiable risk factors for this condition. To determine whether the risk of MGUS is associated with dietary factors in a racially diverse population, we conducted a US population-based case-control study from the National Health and Nutrition Examination Survey (1988-2004), which included 373 individuals with MGUS and 1406 matched controls. Diet was characterized by one 24-hour dietary recall, with gram intake of individual foods and beverages aggregated into groups. Unconditional multivariable logistic regressions were used to model associations between intake of several food groups and MGUS, with odds ratios (ORs) and 95% confidence intervals (CIs) reported for the highest relative to the lowest quantile of intake. Daily gram intake of several food and beverage groups were significantly associated with MGUS. MGUS was inversely associated with whole-grain bread, oats, and rice (OR, 0.70; 95% CI, 0.48-1.00; P < .05), fruits (excluding juice) and vegetables (OR, 0.69; 95% CI, 0.52-0.93; P = .02), vegetables (OR, 0.75; 95% CI, 0.56-0.99; P < .05), tomatoes (OR, 0.72; 95% CI, 0.51-1.00; P < .05), and cruciferous vegetables (OR, 0.44; 95% CI, 0.26-0.74; P < .01). Direct associations were observed for sugar-sweetened beverages (OR, 1.34; 95% CI, 1.00-1.78; P < .05), sugar-sweetened soft drinks (OR, 1.41; 95% CI, 1.01-1.96; P = .04), and artificially sweetened soft drinks (OR, 1.55; 95% CI, 1.04-2.33; P = .03). Our study shows that diet is potentially a modifiable risk factor for MGUS.

Risk prediction models for endometrial cancer: development and validation in an international consortium.

BACKGROUND: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. METHODS: We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses' Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). CONCLUSIONS: Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Sugar Sweetened and Artificially Sweetened Beverage Consumption and Pancreatic Cancer: A Retrospective Study.

Pancreatic cancer (PanCa) is a highly fatal malignancy with few modifiable risk and prognostic factors. This study investigates the association between cola, diet cola, and non-cola soft drink consumption and PanCa risk and mortality. A retrospective study was conducted using data from the Patient Epidemiology Data System (1982-1998) at Roswell Park Comprehensive Cancer Center (Buffalo, NY, USA), including 213 PanCa patients and 852 cancer-free controls. Data were collected using a self-administered questionnaire, including a 46-item food frequency questionnaire (FFQ). Multivariable logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) of cola, diet cola, and non-cola soft drink consumption and PanCa risk. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CIs of cola, diet cola, and non-cola soft drink consumption and PanCa mortality. Stratified analyses were conducted by sex, body mass index (BMI), and smoking status. We observed significant 55% increased odds of PanCa among patients consuming ≥1 regular cola per day (OR: 1.55, 95% CI: 1.01-2.39). We also observed non-significant 38% increased hazard of mortality among patients consuming ≥1 regular cola per day (HR: 1.38, 95% CI: 0.91-2.07). We conclude that regular cola consumption is a modifiable lifestyle that may be associated with PanCa risk and mortality following diagnosis.

Coffee consumption and risk of endometrial cancer: a pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: Epidemiologic studies suggest that coffee consumption may be inversely associated with risk of endometrial cancer (EC), the most common gynecological malignancy in developed countries. Furthermore, coffee consumption may lower circulating concentrations of estrogen and insulin, hormones implicated in endometrial carcinogenesis. Antioxidants and other chemopreventive compounds in coffee may have anticarcinogenic effects. Based on available meta-analyses, the World Cancer Research Fund (WCRF) concluded that consumption of coffee probably protects against EC. OBJECTIVES: Our main aim was to examine the association between coffee consumption and EC risk by combining individual-level data in a pooled analysis. We also sought to evaluate potential effect modification by other risk factors for EC. METHODS: We combined individual-level data from 19 epidemiologic studies (6 cohort, 13 case-control) of 12,159 EC cases and 27,479 controls from the Epidemiology of Endometrial Cancer Consortium (E2C2). Logistic regression was used to calculate ORs and their corresponding 95% CIs. All models were adjusted for potential confounders including age, race, BMI, smoking status, diabetes status, study design, and study site. RESULTS: Coffee drinkers had a lower risk of EC than non-coffee drinkers (multiadjusted OR: 0.87; 95% CI: 0.79, 0.95). There was a dose-response relation between higher coffee consumption and lower risk of EC: compared with non-coffee drinkers, the adjusted pooled ORs for those who drank 1, 2-3, and >4 cups/d were 0.90 (95% CI: 0.82, 1.00), 0.86 (95% CI: 0.78, 0.95), and 0.76 (95% CI: 0.66, 0.87), respectively (P-trend < 0.001). The inverse association between coffee consumption and EC risk was stronger in participants with BMI > 25 kg/m2. CONCLUSIONS: The results of the largest analysis to date pooling individual-level data further support the potentially beneficial health effects of coffee consumption in relation to EC, especially among females with higher BMI.

A Presurgical-Window Intervention Trial of Isothiocyanate-Rich Broccoli Sprout Extract in Patients with Breast Cancer.

SCOPE: Dietary isothiocyanates (ITCs) from cruciferous vegetables have shown potent anti-breast cancer activities in preclinical models, but their anticancer effects in vivo in breast cancer patients remain elusive. A proof-of-principle, presurgical window of opportunity trial is conducted to assess the anticancer effects of dietary ITCs in breast cancer patients. METHODS AND RESULTS: Thirty postmenopausal breast cancer patients are randomly assigned to receive ITC-rich broccoli sprout extract (BSE) (200 µmol ITC per day) or a placebo for 2 weeks. Expression of biomarkers related to ITCs functions are measured in breast cancer tissue specimens at pre- and post-interventions using immunohistochemistry staining. First morning urine samples are collected at both timepoints for proteomic analysis. Overall, the study shows high compliance (100%) and low toxicity (no grade 4 adverse event). Trends of increase in cleaved caspase 3 and tumor-infiltrating lymphocytes (TILs) and trends of decrease in Ki-67 and nuclear to cytoplasm ratio of estrogen receptor (ER)-α are observed in the BSE arm only, consistent with the significantly altered signaling pathways identified in urinary proteomic analysis. CONCLUSIONS: Anticancer activities of ITCs are observed in breast cancer patients, supporting the potential beneficial roles of ITC-containing cruciferous vegetables in breast cancer prognosis.

Cruciferous Vegetable Intervention to Reduce the Risk of Cancer Recurrence in Non-Muscle-Invasive Bladder Cancer Survivors: Development Using a Systematic Process.

BACKGROUND: Bladder cancer is one of the top 10 most common cancers in the United States. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed surgically. However, 50% to 80% of NMIBC cases recur within 5 years, and 15% to 30% progress with poor survival. Current treatments are limited and expensive. A wealth of preclinical and epidemiological evidence suggests that dietary isothiocyanates in cruciferous vegetables (Cruciferae) could be a novel, noninvasive, and cost-effective strategy to control NMIBC recurrence and progression. OBJECTIVE: The aim of this study is to develop a scalable dietary intervention that increases isothiocyanate exposure through Cruciferae intake in NMIBC survivors. METHODS: We worked with a community advisory board (N=8) to identify relevant factors, evidence-based behavior change techniques, and behavioral theory constructs used to increase Cruciferae intake in NMIBC survivors; use the PEN-3 Model focused on incorporating cultural factors salient to the group's shared experiences to review the intervention components (eg, the saliency of behavioral messages); administer the revised intervention to community partners for their feedback; and refine the intervention. RESULTS: We developed a multicomponent intervention for NMIBC survivors consisting of a magazine, tracking book, live telephone call script, and interactive voice messages. Entitled POW-R Health: Power to Redefine Your Health, the intervention incorporated findings from our adaptation process to ensure saliency to NMIBC survivors. CONCLUSIONS: This is the first evidence-based, theoretically grounded dietary intervention developed to reduce bladder cancer recurrence in NMIBC survivors using a systematic process for community adaptation. This study provides a model for others who aim to develop behavioral, community-relevant interventions for cancer prevention and control with the overall goal of wide-scale implementation and dissemination.

Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

BACKGROUND: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. OBJECTIVES: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. METHODS: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. RESULTS: We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary ß-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. CONCLUSIONS: Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.

Sugar-Sweetened Soda Consumption and Total and Breast Cancer Mortality: The Western New York Exposures and Breast Cancer (WEB) Study.

BACKGROUND: There is growing evidence of an association between sugar-sweetened beverages (SSB) and increased risk of mortality in various populations. However, SSB influence on mortality among patients with breast cancer is unknown. METHODS: We assessed the relationship between sugar-sweetened soda and both all-cause and breast cancer mortality among women with incident, invasive breast cancer from the Western New York Exposures and Breast Cancer Study. Breast cancer cases were followed for a median of 18.7 years, with ascertainment of vital status via the National Death Index. Frequency of sugar-sweetened soda consumption was determined via dietary recall using a food frequency questionnaire. Cox proportional hazards, adjusting for relevant variables, were used to estimate HRs and 95% confidence intervals (CI). RESULTS: Of the 927 breast cancer cases, 386 (54.7%) had died by the end of follow-up. Compared with never/rarely sugar-sweetened soda drinkers, consumption at ≥5 times per week was associated with increased risk of both total (HR = 1.62; 95% CI, 1.16-2.26; P trend < 0.01) and breast cancer mortality (HR = 1.85; 95% CI, 1.16-2.94; P trend < 0.01). Risk of mortality was similarly increased among ER-positive, but not ER-negative patients; among women with body mass index above the median, but not below the median; and among premenopausal, but not postmenopausal women for total mortality only. CONCLUSIONS: Reported higher frequency of sugar-sweetened soda intake was associated with increased risks of both total and breast cancer mortality among patients with breast cancer. IMPACT: These results support existing guidelines on reducing consumption of SSB, including for women with a diagnosis of breast cancer.

Glycemic Index, Glycemic Load, and Risk of Ovarian Cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cohort.

BACKGROUND: Ovarian cancer is the fifth most common cause of cancer death among women in the US, yet few modifiable risk factors have been established. Diets high in glycemic index (GI) and glycemic load (GL) have been linked to several cancers, but epidemiologic studies of ovarian cancer have yielded inconsistent results. OBJECTIVE: In this study, we aimed to examine associations between GI or GL and ovarian cancer. METHODS: We used prospective data from the Prostate, Lung, Colorectal, and Ovarian cohort. GI and GL were calculated from validated FFQs. Participants were women who were aged 60 to 74 y, did not have a history of cancer, and had both ovaries. Cox proportional hazard models were used to calculate HRs and 95% CIs for risk of ovarian cancer associated with quartiles of GI and GL. Analyses were performed separately for those who completed the dietary questionnaire at baseline (DQX) or later in the study (DHQ). RESULTS: From the DQX sample set, 181 cases were identified among 24,633 women with median follow-up of 12.1 y; there were 211 cases among 42,410 women in the DHQ set, with median follow-up of 8.9 y. After adjusting for age at dietary questionnaire completion, year of randomization, year of questionnaire, study center, and oral contraceptive use, the risk of ovarian cancer decreased by 43% (HR: 0.57; 95% CI: 0.37, 0.88) among those in the highest compared with those in the lowest quartile of GL (DQX). Those in the highest compared with those in the lowest quartile of GI (DHQ), had a 38% lower risk (HR: 0.62; 95% CI: 0.42, 1.00). CONCLUSIONS: We observed lower risk of ovarian cancer associated with higher GI and GL. Results should be interpreted with caution as they may have been influenced by limitations including lack of variability in dietary intake. Additional studies are needed to better understand what is driving these associations.

Cruciferous vegetable consumption and pancreatic cancer: A case-control study.

BACKGROUND: Pancreatic cancer is a deadly malignancy with limited screening and few modifiable risk factors. The objective of this study was to investigate the association between a modifiable lifestyle behavior, cruciferous vegetable consumption, and pancreatic cancer, both overall and by subgroups based on non-modifiable, established risk factors. METHODS: We conducted a hospital-based, case-control study utilizing data from the Patient Epidemiology Data System (1982-1998) at Roswell Park Comprehensive Cancer Center (Buffalo, NY) which included 183 pancreatic cancer patients and 732 cancer-free controls. Data were collected using a self-administered questionnaire including a 52-item food frequency questionnaire and other epidemiologic data. Multivariable logistic regression, adjusted for age, body mass index (BMI), sex, smoking status, total meat, and family history of pancreatic cancer, was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between cruciferous vegetable consumption and pancreatic cancer. Subgroup analyses were conducted by sex, smoking status, and BMI. RESULTS: We observed inverse associations between cruciferous vegetable intake and pancreatic cancer, with a significant 40% lower odds of pancreatic cancer among subjects consuming >1.5 servings per week (SPW) of raw cruciferous vegetables compared to those consuming less than 0.5 SPW (OR = 0.60, 95% CI: 0.39-0.93). Each additional SPW of total, raw, and cooked cruciferous vegetables was associated with a significant 7-15% lower odds of pancreatic cancer, with the strongest association seen in raw cruciferous vegetables (OR = 0.85, 95% CI: 0.75-0.95). We observed inverse associations between raw cruciferous vegetable intake and pancreatic cancer among people who were overweight, former smokers, and males, ranging from 50% to 59% lower odds. CONCLUSION: Consuming cruciferous vegetables, especially raw cruciferous vegetables, is a modifiable lifestyle behavior which may be inversely associated with pancreatic cancer, including among subgroups with other non- or not easily modifiable risk factors for this deadly malignancy.

Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival.

BACKGROUND: Although physical activity has been consistently associated with reduced breast cancer mortality, evidence is largely based on data collected at one occasion. We examined how pre- and postdiagnosis physical activity was associated with survival outcomes in high-risk breast cancer patients. METHODS: Included were 1340 patients enrolled in the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) Study, a prospective study of lifestyle and prognosis ancillary to a SWOG clinical trial (S0221). Activity before diagnosis, during treatment, and at 1- and 2-year intervals after enrollment was collected. Patients were categorized according to the Physical Activity Guidelines for Americans as meeting the minimum guidelines (yes/no) and incrementally as inactive, low active, moderately active (meeting the guidelines), or high active. RESULTS: In joint-exposure analyses, patients meeting the guidelines before and 1 year after diagnosis experienced statistically significant reductions in hazards of recurrence (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.42 to 0.82) and mortality (HR = 0.51, 95% CI = 0.34-0.77); associations were stronger at 2-year follow-up for recurrence (HR = 0.45, 95% CI = 0.31 to 0.65) and mortality (HR = 0.32, 95% CI = 0.19 to 0.52). In time-dependent analyses, factoring in activity from all time points, we observed striking associations with mortality for low- (HR = 0.41, 95% CI = 0.24 to 0.68), moderate- (HR = 0.42, 95% CI = 0.23 to 0.76), and high-active patients (HR = 0.31, 95% CI = 0.18 to 0.53). CONCLUSIONS: Meeting the minimum guidelines for physical activity both before diagnosis and after treatment appears to be associated with statistically significantly reduced hazards of recurrence and mortality among breast cancer patients. When considering activity from all time points, including during treatment, lower volumes of regular activity were associated with similar overall survival advantages as meeting and exceeding the guidelines.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Menthol Cigarettes and Smoking Cessation among Adult Smokers in the US.

Objectives: In this study, we identified differences in cessation, nicotine dependence, and quit attempts between smokers using non-menthol cigarettes and smokers using menthol cigarettes differing in menthol delivery method (eg, menthol in the tobacco only, crushable capsules only or both). Methods: We analyzed data from the Population Assessment of Tobacco and Health Study, Waves 1 and 2 (W1 and W2), to determine associations of delivery method of menthol with cessation, nicotine dependence, and quit attempts among current adult cigarette smokers. Results: Nearly 40% of US smokers reported using a mentholated cigarette product with most using a product mentholated in the tobacco only. Smokers included in this analysis had a moderate to low heaviness of smoking index score. The lowest average score was among those using products mentholated in a filter capsule only (1.3, SE = .10), and the highest among those using non-mentholated products (2.4, SE = .03). About 12% of smokers quit between W1 and W2. Cessation, nicotine dependence, and quit attempts at W2 were not associated with delivery method of menthol at W1. Conclusions: Method of menthol delivery did not impact cessation, nicotine dependence, and quit attempts.

Cruciferous Vegetable Consumption and Stomach Cancer: A Case-Control Study.

Objective: To investigate the association between regular cruciferous vegetable intake and stomach cancer.Methods: A hospital-based, case-control study was conducted at Roswell Park Comprehensive Cancer Center in Buffalo, NY, which included 292 stomach cancer patients and 1168 cancer-free controls recruited between 1992 and 1998 as part of the Patient Epidemiology Data System (PEDS). Dietary and other epidemiologic and confounding variables were collected by questionnaire. Multivariable logistic regression analyses were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between usual pre-diagnostic cruciferous vegetable intake and stomach cancer, with adjustment for other stomach cancer risk factors and dietary characteristics.Results: We observed strong inverse associations between stomach cancer and highest versus lowest intakes of total cruciferous vegetables (OR = 0.59, 95% CI: 0.42-0.83), raw cruciferous vegetables (OR = 0.53, 95% CI: 0.38-0.73), raw broccoli (OR = 0.61, 95% CI: 0.43-0.86), raw cauliflower (OR = 0.51, 95% CI: 0.35-0.73), and Brussels sprouts (OR = 0.66, 95% CI = 0.48-0.91).Conclusions: These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer, even after considering other dietary characteristics.

Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221).

PURPOSE: Despite reported widespread use of dietary supplements during cancer treatment, few empirical data with regard to their safety or efficacy exist. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes. METHODS: Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cox proportional hazards regression adjusting for clinical and lifestyle variables was used. Recurrence and survival were indexed at 6 months after enrollment using a landmark approach. RESULTS: There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P = .06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P = .14). Relationships with individual antioxidants were weaker perhaps because of small numbers. For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P < .01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P < .01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P < .01) as was use both before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P = .06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes. CONCLUSION: Associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.

Menthol, Nicotine, and Flavoring Content of Capsule Cigarettes in the US.

OBJECTIVES: Characterize physical design features of cigarette brands sold in the US according to the delivery method of menthol that may affect sensory perception among users. METHODS: Twelve cigarette brands, mentholated and non-mentholated, were purchased for analyses of the physical design characteristics, quantification of nicotine and menthol, and identification of flavor additives. RESULTS: Physical design characteristics did not differ significantly between the various cigarette brands. However, significant differences were seen in levels of menthol. Menthol levels were greatest in products that had dual delivery methods of menthol (6.7mg/cigarette; SE=0.27) followed by products mentholated in a filter capsule only (5.7mg/cigarette; SE=0.25), and those mentholated in the tobacco only (3.8mg/cigarette; SE=0.12); products that were not mentholated had the least (0.38mg/cigarette; SE=0.31). Finally, flavor additives with a mint flavor profile other than menthol were identified, such as pulegone and limonene, and differed between cigarette brands, which are likely contributing to the menthol flavor experience associated with use of these products. CONCLUSIONS: The regulation of menthol delivery method, flavorings added to the capsule, and/or menthol concentration may be beneficial for the public health as these factors are likely creating unique sensory experiences.

Genetic Variation in Steroid and Xenobiotic Metabolizing Pathways and Enterolactone Excretion Before and After Flaxseed Intervention in African American and European American Women.

BACKGROUND: Metabolism and excretion of the phytoestrogen enterolactone (ENL), which has been associated with breast cancer risk, may be affected by variation in steroid hormone and xenobiotic-metabolizing genes. METHODS: We conducted a randomized, crossover flaxseed intervention study in 252 healthy, postmenopausal women [137 European ancestry (EA) and 115 African ancestry (AA)] from western New York. Participants were randomly assigned to maintain usual diet or consume 10 g/day ground flaxseed for 6 weeks. After a 2-month washout period, participants crossed over to the other diet condition for an additional 6 weeks. Urinary ENL excretion was measured by gas chromatography-mass spectrometry and 70 polymorphisms in 29 genes related to steroid hormone and xenobiotic metabolism were genotyped. Mixed additive genetic models were constructed to examine association of genetic variation with urinary ENL excretion at baseline and after the flaxseed intervention. RESULTS: SNPs in several genes were nominally (P < 0.05) associated with ENL excretion at baseline and/or after intervention: ESR1, CYP1B1, COMT, CYP3A5, ARPC1A, BCL2L11, SHBG, SLCO1B1, and ZKSCAN5. A greater number of SNPs were associated among AA women than among EA women, and no SNPs were associated in both races. No SNP-ENL associations were statistically significant after correction for multiple comparisons. CONCLUSIONS: Variation in several genes related to steroid hormone metabolism was associated with lignan excretion at baseline and/or after flaxseed intervention among postmenopausal women. IMPACT: These findings may contribute to our understanding of the differences observed in urinary ENL excretion among AA and EA women and thus hormone-related breast cancer risk.