Systemic Lupus Erythematosus and the Ratio of Omega-3 to Omega-6 Fatty Acids Consumption among Women in the Adventist Health Study-2.

OBJECTIVE: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis. METHODS: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI). RESULTS: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50-59 years compared to those 30-49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases. CONCLUSION: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?

INTRODUCTION: The effects of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) on cerebrovascular disease remain unsettled. However, most studies have focused on marine sourced n-3 PUFA rather than total n-3 PUFA, of which the majority in the American diet is plant derived. This study therefore intended to investigate these effects in a cohort for which the vegetarian diet was more prevalent than the general public. METHODS: Cox proportional hazards with fatal stroke as the outcome was performed on the approximately 96,000 subject Adventist Health Study 2 prospective cohort. Stratification by race and sex was performed on models with a priori covariables, comparing 90th to 10th percentile daily intakes of energy-adjusted total n-3 PUFA, total n-6 PUFA, and the n-6 / n-3 PUFA ratio as variables of interest. RESULTS: For the main analytical group (78,335 subjects), the hazard ratio (95% confidence interval) for total n-3 PUFA was 0.65 (0.51-0.83), and for total n-6 PUFA was 1.37 (1.02-1.82), while adjusting for both fatty acids in the model. The n-6 / n-3 PUFA ratio was harmful with a HR of 1.40 (1.16-1.69), whereas the inclusion of total n-3 PUFA slightly attenuated the HR to 1.33(1.02-1.74). Effects were similar for the non-black sex-combined and sex-specific analyses. CONCLUSION: In most analytic groups, subjects with greater total n-3 PUFA intakes have lower risk of fatal stroke, and those with a higher n-6 / n-3 PUFA ratio had higher risk. However, the n-6 / n-3 PUFA ratio remains statistically significant even after adjusting for total n-3 PUFA or total n-6 PUFA, suggesting that the ratio is of epidemiologic interest for cerebrovascular disease research.

The association between dietary patterns and a doctor diagnosis of systemic lupus erythematosus: the Adventist Health Study-2.

OBJECTIVE: The aim of our study was to assess the association between a diagnosis of Systemic Lupus Erythematosus (SLE) and dietary pattern as well as demographic factors among subjects in the Adventist Health Study-2 (AHS-2) cohort. METHODS: Multivariable logistic regression modeling was used to assess the association between prevalence of self-reported SLE and dietary patterns (vegetarian, pesco-vegetarian and non-vegetarian). Potential confounding variables included were age, gender, race, education, and smoking history among 77,795 AHS-2 participants. RESULTS: There was a dose-response association between the prevalence of SLE with vegetarian diets, ordered by content of animal meats. The stricter vegetarians had 25% lower odds of reporting that they were currently being treated for SLE (OR = 0.75, 95% CI 0.56, 1.02) with intermediate levels for the pesco-vegetarians who eat fish (OR 0.88, 95% CI 0.57, 1.36), compared to non-vegetarians. As expected, there were also significant associations between the prevalence of SLE with sex, race, age, and smoking. Significantly fewer men were diagnosed with SLE compared to women (OR = 0.14, 95% CI: 0.08, 0.22). Compared to non-Hispanic Whites, non-Hispanic Blacks were significantly more likely to report a diagnosis of SLE (OR 1.69, 95% CI 1.29, 2.21). A significantly lower proportion of 30-39 year olds (OR 0.51, 95% CI 0.29, 0.90) reported a diagnosis of SLE when compared to those 60 or older. Also, ever smokers were more likely to report prevalent SLE than those who had never smoked (OR 1.71, 95% CI 1.27, 2.31). CONCLUSION: We found that vegetarians had lower odds of doctor-diagnosed SLE with an increasing trend in prevalence from stricter vegetarians to pesco-vegetarians to non-vegetarians. We also note that the association with other demographic factors in AHS-2 was similar to that found in other studies. Future studies may focus on assessing the incidence and severity of the disease among vegetarians and non-vegetarians.

Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2.

BACKGROUND: Prostate cancer is the most common noncutaneous cancer in American males. Causal links between dairy, or dietary calcium, and this cancer are considered suggestive but limited. OBJECTIVES: To evaluate these associations in a large North American cohort, including many with no (or very low) dairy intake and much calcium from nondairy sources. METHODS: A prospective cohort study of 28,737 Seventh-day Adventist men in the United States and Canada, of whom 6389 were of black ethnicity. Diet was measured by FFQ, and 275 male participants also provided repeated 24-h dietary recalls as a calibration substudy. Incident cancers were mainly found by matching with cancer registries. Analyses used multivariable proportional hazards regressions and regression calibration for some analyses. RESULTS: In total, 1254 (190 advanced) incident prostate cancer cases were found during an average 7.8 y of follow-up. Men at the 90th percentile of dairy intake (430 g/d) compared with the 10th percentile (20.2 g/d) had higher prostate cancer risk (HR: 1.27; 95% CI: 1.12, 1.43). Similar findings, comparing the same g/d intakes, were demonstrated for advanced prostate cancers (HR: 1.38; 95% CI: 1.02, 1.88), for nonadvanced cases (HR: 1.27; 95% CI: 1.11, 1.45), in black participants (HR: 1.24; 95% CI: 0.98, 1.58), and when excluding vegan participants (HR: 1.22; 95% CI: 1.03, 1.43). Calibrated dairy (g/d) regressions (all participants and all prostate cancers), adjusting for dietary measurement error, found a HR of 1.75 (95% CI: 1.32, 2.32). Comparing 90th percentile intake to zero intakes (uncalibrated), the HR was 1.62 (95% CI: 1.26, 2.05). There was no evidence of an effect of higher (905 mg/d) compared with lower (349 mg/d) intakes of nondairy calcium (HR: 1.16; 95% CI: 0.94, 1.44). CONCLUSIONS: Men with higher intake of dairy foods, but not nondairy calcium, had a higher risk of prostate cancer compared with men having lower intakes. Associations were nonlinear, suggesting greatest increases in risk at relatively low doses.

Lower Compliance with Cervical Cancer Screening Guidelines Among Vegetarians in North America.

Cervical cancer is preventable and treatable through regular screening and follow-up. However, the utilization of cervical cancer screening may vary widely based on individual lifestyles. The purpose of this study was to examine the differences in the adherence to cervical cancer screening guidelines in various dietary groups. Our study included 21,376 women from the United States and Canada, aged 30-69 from the Adventist Health Study-2, a large population-based prospective cohort study. Modified Poisson regression with robust variance estimation was used to determine the prevalence ratios of cervical cancer screening behavior in participants following five different dietary patterns (non-vegetarians, semi-vegetarians, pesco-vegetarians, lacto-ovo-vegetarians, and vegans). All analyses were adjusted for age, race/ethnicity, marital status, education, personal income, body mass index, smoking, alcohol use, exercise, and family history of all female cancer. Vegetarians, in general, had similar screening prevalence as non-vegetarians. However, vegans were 16% less likely to have had a Pap test compared to non-vegetarians (prevalence ratio (PR) = 0.84, 95% confidence interval 0.81-0.86). Women who were younger, Black, married, more educated, had a family history of all female cancer, had a higher income, and exercise reported higher compliance to a Pap test. It remains to be seen whether vegan women in Adventist Health-2 experience a higher incidence of cervical cancer or are diagnosed at a later stage compared to non-vegetarians.

Glycemic status, non-traditional risk and left ventricular structure and function in the Jackson Heart Study.

BACKGROUND: Left ventricular structure and function abnormalities may be an early marker of cardiomyopathy among African Americans with diabetes (DM) even in the absence of coronary artery disease (CAD), arrhythmia, valvular heart disease and end-stage renal disease (ESRD). This study examined the association of prediabetes (PDM), DM and HbA1c with left ventricular structure and function among Jackson Heart Study (JHS) participants without traditional risk factors. METHODS: Retrospective cross-sectional analyses of the association of PDM, DM and HbA1c with, left ventricular ejection fraction (LV EF), fractional shortening (LV FS), stroke volume index (SVI), cardiac index (CI), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), relative wall thickness (RWT), myocardial contraction fraction (MCF) and left ventricular mass index (LVMI). The study was conducted in 2234 adult JHS participants without preexisting CAD, arrhythmia, valvular heart disease or ESRD. Statistical analyses included descriptive, univariate and covariate adjusted linear regression analyses. Sensitivity analyses to explore the impact of hypertension on study outcomes were also carried out. RESULTS: DM compared with no DM was associated with lower, SVI (- 0.96 ml/m2, p = 0.029), LVEDVI (- 1.44 ml/m2 p = 0.015), and MCF (- 1.90% p = 0.007) but higher CI (0.14 L/min/m2, p < 0.001), RWT (0.01 cm, p = 0.002) and LVMI (2.29 g/m2, p = 0.009). After further control for DM duration, only CI remaining significantly higher for DM compared with no DM participants (0.12 L/min/m2, p = 0.009). PDM compared with no PDM was associated with lower, SVI (- 0.87 ml/m2, P = 0.024), LVEDVI (- 1.15 ml/m2 p = 0.003) and LVESVI (- 0.62 ml/m2 p = 0.025). HbA1c ≥ 8.0% compared with HbA1c < 5.7% was associated with lower SVI (- 2.09 ml/m2, p = 0.004), LVEDVI (- 2.11 ml/m2 p = 0.032) and MCF (- 2.94% p = 0.011) but higher CI (0.11 L/min/m2, p = 0.043) and RWT (0.01 cm, p = 0.035). CONCLUSIONS: Glycemic status is associated with important left ventricular structure and function changes among African Americans without prior CAD, arrhythmia, valvular heart disease and ESRD. Longitudinal studies may further elucidate these relationships.

Lower Utilization of Colorectal Cancer Screening Among Vegetarians, Adventist Health Study-2.

This study aims to examine lifestyle predictors of the utilization of colorectal cancer screening. Using modified Poisson regression, we studied self-reported colorectal cancer screening utilization (colonoscopy or fecal occult blood test) with various dietary and lifestyle characteristics among 33,922 subjects aged 51 + years in the Adventist Health Study-2, a large population-based prospective cohort study. According to the multivariable-adjusted models, vegetarians were less likely to report screening: vegans, prevalence ratio (PR) = 0.80 (95% confidence interval 0.77-0.83); lacto-ovo-vegetarians (0.95 [0.93-0.97]); and semi-vegetarians (0.97 [0.94-0.99]) compared to non-vegetarians. Blacks were more likely than non-Blacks to be screened (1.04 [1.02-1.06]) and males were less likely (0.93 [0.92-0.95]) to utilize the screening tests. Older subjects were more likely to be screened, and unmarried and divorced/widowed subjects were less likely to screen. Education, personal income, and BMI were positively associated with screening, with p-value for trend < 0.001 for all three variables. A family history of colorectal cancer was associated with higher screening prevalence (1.15 [1.12-1.17]). Our stratified analyses on race and gender with dietary patterns showed non-Hispanic White vegans (PR = 0.77 [0.74-0.81]) and male vegans (PR = 0.76 [0.72-0.81]) were least likely compliant with colorectal cancer screening (p = 0.009 and p = 0.04, respectively). Vegans may believe that their personal risk for colorectal cancer is low due to their healthy lifestyle, resulting in lack of compliance to colorectal cancer screening. It remains to be seen whether vegans in AHS-2 also experience higher incidence of colorectal cancer or are diagnosed at a later stage.

Validity of FFQ Estimates of Total Sugars, Added Sugars, Sucrose and Fructose Compared to Repeated 24-h Recalls in Adventist Health Study-2 Participants.

Sugar intake is a potentially important aspect of diet which has not previously been validated in the Adventist Health Study-2 (AHS-2). We sought to validate the food frequency questionnaire (FFQ) measurement of total sugars, added sugars, sucrose, and fructose against multiple 24-h dietary recalls (recalls) in AHS-2 participants. Food consumption data from a self-administered FFQ and six recalls from 904 participants were combined with nutrient profile data to estimate daily sugar intake. Validity was evaluated among all participants and by race. FFQ and recall means were compared and correlation coefficients (Spearman's, energy-adjusted log-transformed Pearson's, deattenuated Pearson's) were calculated. Mean total energy, total sugars, and fructose intake were higher in the FFQ, whereas added sugars and sucrose were higher in recalls. The energy-adjusted (log-transformed) deattenuated correlations among all participants were: total sugars (r = 0.42, 95% CI 0.32-0.52), added sugars (r = 0.50, 95% CI 0.36-0.59), sucrose (r = 0.32, 95% CI 0.23-0.42), and fructose (r = 0.50, 95% CI 0.40-0.59). We observed moderate validity for added sugars and fructose and low-moderate validity for total sugars and sucrose measured by the AHS-2 FFQ in this population. Dietary sugar estimates from this FFQ may be useful in assessing possible associations of sugars intake with health outcomes.

Dietary patterns and hip fracture in the Adventist Health Study 2: combined vitamin D and calcium supplementation mitigate increased hip fracture risk among vegans.

BACKGROUND: Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue. OBJECTIVES: We aimed to explore the influence of 5 previously defined dietary patterns on hip fracture risk and whether this association is modified by concomitant calcium and vitamin D supplementation. METHODS: The Adventist Health Study 2 is a prospective cohort study in which participants were enrolled during 2002-2007; proportional hazards regression analyses were used to estimate fracture risk. Participants reside throughout the United States and Canada. A total of 34,542 non-Hispanic white peri- and postmenopausal women and men 45 y and older responded to the biennial hospital history form and were followed for a median of 8.4 y. RESULTS: The study identified 679 incident hip fractures during 249,186 person-years of follow-up. Fracture risk varied according to dietary pattern, with a clear effect modification by concurrent supplementation with both vitamin D and calcium. In multivariable models, including adjustment for calcium and vitamin D supplementation, female vegans had 55% higher risk of hip fracture (HR: 1.55; 95% CI: 1.06, 2.26) than nonvegetarians (NVEGs), whereas there was no association between diet pattern and hip fracture risk in men. When further stratifying females on supplement use with both vitamin D and calcium, vegans taking both supplements were at no greater risk of hip fracture than the subjects with other dietary patterns including the NVEGs. CONCLUSIONS: Without combined supplementation of both vitamin D and calcium, female vegans are at high risk of hip fracture. However, with supplementation the excessive risk associated with vegans disappeared. Further research is needed to confirm the adequacy of a vegan diet supplemented with calcium and vitamin D with respect to risk of fracture.

Racial Difference in the Association of Long-Term Exposure to Fine Particulate Matter (PM2.5) and Cardiovascular Disease Mortality among Renal Transplant Recipients.

Ambient air pollutants are known risk factors for cardiovascular disease (CVD) morbidity and mortality with significant racial disparities. However, few studies have explored racial differences among highly susceptible subpopulations, such as renal transplant recipients (RTRs). Despite improvements in quality of life after transplantation, CVD remains the major cause of mortality, especially among Black recipients. This study aimed to evaluate potential racial differences in the association between long-term levels of PM2.5 and the risk of all-cause, total CVD, and coronary heart disease (CHD) mortality among RTRs. This retrospective study consists of 93,857 non-smoking adults who received a renal transplant between 2001 and 2015. Time-dependent Cox regression was used to assess the association between annual concentrations of PM2.5 and mortality risk. In the multivariable-adjusted models, a 10 µg/m3 increase in ambient PM2.5 levels found increased risk of all-cause (HR = 3.45, 95% CI: 3.08-3.78), CVD (HR = 2.38, 95% CI: 1.94-2.92), and CHD mortality (HR = 3.10, 95% CI: 1.96-4.90). Black recipients had higher risks of all-cause (HR = 4.09, 95% CI: 3.43-4.88) and CHD mortality (HR = 6.73, 95% CI: 2.96-15.32). High levels of ambient PM2.5 were associated with all-cause, CVD, and CHD mortality. The association tended to be higher among Black recipients than non-Blacks.

Recommended Definitions of Aggressive Prostate Cancer for Etiologic Epidemiologic Research.

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute's Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Tomato consumption and intake of lycopene as predictors of the incidence of prostate cancer: the Adventist Health Study-2.

PURPOSE: Studies have controversially suggested that prostate cancer, the most common cancer among Western men, is less common among those with a high intake of tomato products and lycopene. We examine multivariable associations between the intake of tomatoes and lycopene, and risk of prostate cancer. METHODS: In a prospective study of 27,934 Adventist men without prevalent cancer, Cox proportional hazard regression analyses were used to address the objectives. Dietary measurement error was partially corrected with regression calibration. RESULTS: 1226 incident cases of prostate cancer, 355 of them aggressive, were identified during 7.9 years of follow-up. Consumption of canned and cooked tomatoes more than four times a week was associated with a HR = 0.72 (95% CI 0.55, 0.94, P = 0.02) comparing to risk in those never consuming this food. Treating this as a continuous variable, adjusting for confounders, produces a similar result, HR = 0.86 (95% CI 0.75, 0.99), comparing 64 g/day with zero intakes (questionnaire data). Regression calibration, although less precise, suggests a yet stronger and statistically significant inverse relationship, comparing a 24-h dietary recall intake of 71 g/day canned and cooked tomato product, with zero intake. Uncalibrated multivariable-adjusted competing risk analyses do not find differences in tomato associations between aggressive and non-aggressive prostate cancers although power for aggressive cancers is limited. CONCLUSION: Consumption of canned and cooked tomatoes may reduce the risk of prostate cancer. These products contain more available lycopene. However, an observational study cannot exclude confounding by some unidentified, prostate cancer preventive factor. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT03615599.

Dairy, soy, and risk of breast cancer: those confounded milks.

BACKGROUND: Associations between soy, dairy intakes and breast cancer risk are inconsistent. No studies exist with large numbers of dairy consumers and soy consumers to assess mutual confounding. METHODS: The study cohort contains 52 795 North American women, initially free of cancer, followed for 7.9 years (29.7% were Black). Dietary intakes were estimated from food frequency questionnaires and, for 1011 calibration study subjects, from six structured 24-h dietary recalls. Incident invasive breast cancers were detected mainly by matching with cancer registries. Analyses used multivariable proportional hazards regression. RESULTS: The participants (mean age of 57.1 years) experienced 1057 new breast cancer cases during follow-up. No clear associations were found between soy products and breast cancer, independently of dairy. However, higher intakes of dairy calories and dairy milk were associated with hazard ratios (HRs) of 1.22 [95% confidence interval (CI): 1.05-1.40] and 1.50 (95% CI 1.22-1.84), respectively, comparing 90th to 10th percentiles of intakes. Full fat and reduced fat milks produced similar results. No important associations were noted with cheese and yogurt. Substituting median intakes of dairy milk users by those of soy milk consumers was associated with HR of 0.68 (95% CI: 0.55-0.85). Similar-sized associations were found among pre- and post-menopausal cases, with CIs also excluding the null in estrogen receptor (ER+, ER-), and progesterone receptor (PR+) cancers. Less biased calibrated measurement-error adjusted regressions demonstrated yet stronger, but less precise, HRs and CIs that still excluded the null. CONCLUSIONS: Higher intakes of dairy milk were associated with greater risk of breast cancer, when adjusted for soy intake. Current guidelines for dairy milk consumption could be viewed with some caution.

The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3).

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.

Quality of life and psychological outcomes of body-weight supported locomotor training in spinal cord injured persons with long-standing incomplete lesions.

STUDY DESIGN: Health-related quality of life (HRQOL) data from two parallel independent single-blinded controlled randomized studies of manual (Study 1) and robotic (Study 2) locomotor training were combined (ClinicalTrials.gov #NCT00854555). OBJECTIVE: To assess effects of body-weight supported locomotor training (BWSLT) programs on HRQOL in persons with long-standing motor incomplete spinal cord injury and poor walking function. SETTINGS: Two inpatient rehabilitation facilities and one outpatient clinic in Norway. METHODS: Data were merged into intervention (locomotor training 60 days) or control group ("usual care"). Participants completed questionnaires before randomization and 2-4 weeks after the study period, including demographic characteristics, HRQOL (36-Item Short-Form Health Status Survey, SF-36), physical activity (The International Physical Activity Questionnaire Short Form, IPAQ-SF), exercise barrier self-efficacy (EBSE), and motivation for training (Behavioral Regulation in Exercise Questionnaire, BREQ). Physical outcomes i.e., Lower extremity motor score (LEMS) was assessed. The main outcome was change in HRQOL. Secondary outcomes included changes in IPAQ-SF, EBSE, BREQ, and physical outcomes. RESULTS: We recruited 37 of 60 predetermined participants. They were autonomously motivated with high baseline physical activity. BWSLT with manual or robot assistance did not improve HRQOL, though LEMS increased in the BWSLT group compared with control group. CONCLUSIONS: The study was underpowered due to recruitment problems. The training programs seem to benefit LEMS, but not other physical outcomes, and had minimal effects on HRQOL, EBSE, and motivation. Autonomous motivation and high physical activity prior to the study possibly limited the attainable outcome benefits, in addition to limitations due to poor baseline physical function.

Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies.

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.