Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

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.

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.

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.

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.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

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.

Cross-sectional comparisons of subgingival microbiome and gingival fluid inflammatory cytokines in periodontally healthy vegetarians versus non-vegetarians.

BACKGROUND: Vegetarian diets are known to reduce inflammation. The objective of this study was to test the hypothesis that reduced inflammation associated with a vegetarian diet would promote a more commensal subgingival bacterial profile. METHODS: A total of 39 periodontally healthy subjects (PD ≤3 mm, bleeding on probing <10%) were enrolled. Dietary intake was assessed by a food frequency questionnaire. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and subgingival plaque samples were collected. GCF samples were assessed for interleukin-1ß, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and interleukin-10. Plaque samples were analyzed for bacteria using 16S rDNA sequencing on an Illumina platform. GenBank database was used for taxonomy classification. RESULTS: Twenty-three subjects were categorized as vegetarian and 16 non-vegetarians. Clinical periodontal measures and GCF cytokine levels were statistically comparable between the two groups. Measures of microbial richness and alpha diversity were also comparable between the two dietary groups. Vegetarians harbored higher levels of phyla associated with gingival health (Actinobacteria, and Proteobacteria). Two species known to be associated with periodontitis (Mogibacterium timidum and Veillonella rogosae) were prominent in non-vegetarians. Pearson's correlations between GCF inflammatory cytokines and microbial taxa differed between vegetarians and non-vegetarians. In vegetarians, the anti-inflammatory cytokine IL-10 positively correlated with two species known to be associated with periodontal health (Peptidiphaga sp. HMT183 and Rothia aeria). CONCLUSIONS: Diet is directly and indirectly associated with the microbial composition of subgingival plaque. A vegetarian diet may promote a subgingival microbiota associated with periodontal health.

Human-specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression.

Compared with our closest living evolutionary cousins, humans appear unusually prone to develop carcinomas (cancers arising from epithelia). The SIGLEC12 gene, which encodes the Siglec-XII protein expressed on epithelial cells, has several uniquely human features: a fixed homozygous missense mutation inactivating its natural ligand recognition property; a polymorphic frameshift mutation eliminating full-length protein expression in ~60%-70% of worldwide human populations; and, genomic features suggesting a negative selective sweep favoring the pseudogene state. Despite the loss of canonical sialic acid binding, Siglec-XII still recruits Shp2 and accelerates tumor growth in a mouse model. We hypothesized that dysfunctional Siglec-XII facilitates human carcinoma progression, correlating with known tumorigenic signatures of Shp2-dependent cancers. Immunohistochemistry was used to detect Siglec-XII expression on tissue microarrays. PC-3 prostate cancer cells were transfected with Siglec-XII and transcription of genes enriched with Siglec-XII was determined. Genomic SIGLEC12 status was determined for four different cancer cohorts. Finally, a dot blot analysis of human urinary epithelial cells was established to determine the Siglec-XII expressors versus non-expressors. Forced expression in a SIGLEC12 null carcinoma cell line enriched transcription of genes associated with cancer progression. While Siglec-XII was detected as expected in ~30%-40% of normal epithelia, ~80% of advanced carcinomas showed strong expression. Notably, >80% of late-stage colorectal cancers had a functional SIGLEC12 allele, correlating with overall increased mortality. Thus, advanced carcinomas are much more likely to occur in individuals whose genomes have an intact SIGLEC12 gene, likely because the encoded Siglec-XII protein recruits Shp2-related oncogenic pathways. The finding has prognostic, diagnostic, and therapeutic implications.

Validation of estimated glycaemic index and glycaemic load, stratified by race, in the Adventist Health Study-2 (AHS-2).

OBJECTIVE: Few studies have validated FFQ estimates of dietary glycaemic index (GI) and load (GL). We investigated how well our estimates of overall GI and GL from FFQs correlate with estimates from repeated 24 h recall data to validate overall GI and GL in the Adventist Health Study-2 (AHS-2). DESIGN: The AHS-2 is a prospective population-based cohort of 95 873 Seventh-day Adventist adult church members enrolled from 2002 to 2007 to investigate diet, cancer and mortality. SETTING: A 204-item FFQ was used to assess race- and gender-specific validity of GI and GL and 24 h recall data, from the calibration sub-study, were used as the reference. PARTICIPANTS: The 734 calibration study participants were randomly selected by church and included approximately equal numbers of blacks and whites but were otherwise similar to the whole cohort with respect to gender, age, education and vegetarian status. RESULTS: The deattenuated correlation coefficients for overall GI ranged from 0·19 (95 % CI -0·06, 0·53) in black men to 0·46 (95 % CI 0·40, 0·60) in black women, with both non-black men and women falling between those values (0·45 (95 % CI 0·35, 0·65) and 0·38 (95 % CI 0·27, 0·57), respectively). GL correlations were somewhat higher for all study participants. When looking at the entire cohort, the deattenuated validity correlation value for overall GI was (r 0·38, 95 % CI 0·36, 0·47) and GL was (r 0·39, 95 % CI 0·34, 0·49). CONCLUSIONS: Our findings support the cautious use of our FFQ in epidemiological studies when assessing associations of overall GI and GL with disease risk. However, observed differences by race should be considered when interpreting results.

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.

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.

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.

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.

Lower rates of cancer and all-cause mortality in an Adventist cohort compared with a US Census population.

BACKGROUND: Previous research suggests that Adventists, who often follow vegetarian diets, live longer and have lower risks for many cancers than others, but there are no national data and little published comparative data for black subjects. METHODS: This study compared all-cause mortality and cancer incidence between the nationally inclusive Adventist Health Study 2 (AHS-2) and nonsmokers in US Census populations: the National Longitudinal Mortality Study (NLMS) and its Surveillance, Epidemiology, and End Results substudy. Analyses used proportional hazards regression adjusting for age, sex, race, cigarette smoking history, and education. RESULTS: All-cause mortality and all-cancer incidence in the black AHS-2 population were significantly lower than those for the black NLMS populations (hazard ratio [HR] for mortality, 0.64; 95% confidence interval [CI], 0.59-0.69; HR for incidence, 0.78; 95% CI, 0.68-0.88). When races were combined, estimated all-cause mortality was also significantly lower in the AHS-2 population at the age of 65 years (HR, 0.67; 95% CI, 0.64-0.69) and at the age of 85 years (HR, 0.78; 95% CI, 0.75-0.81), as was cancer mortality; this was also true for the rate of all incident cancers combined (HR, 0.70; 95% CI, 0.67-0.74) and the rates of breast, colorectal, and lung cancers. Survival curves confirmed the mortality results and showed that among males, AHS-2 blacks survived longer than white US subjects. CONCLUSIONS: Substantially lower rates of all-cause mortality and cancer incidence among Adventists have implications for the effects of lifestyle and perhaps particularly diet on the etiology of these health problems. Trends similar to those seen in the combined population are also found in comparisons of black AHS-2 and NLMS subjects.

Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit.

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

Vegetarian Epidemiology: Review and Discussion of Findings from Geographically Diverse Cohorts.

Epidemiologic cohort studies enrolling a large percentage of vegetarians have been highly informative regarding the nutritional adequacy and possible health effects of vegetarian diets. The 2 largest such cohorts are the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford) and the Adventist Health Study-2 (AHS-2). These cohorts are described and their findings discussed, including a discussion of where findings appear to diverge. Although such studies from North America and the United Kingdom have been important, the large majority of the world's vegetarians live in other regions, particularly in Asia. Findings from recent cohort studies of vegetarians in East and South Asia are reviewed, particularly the Tzu Chi Health Study and Indian Migration Study. Important considerations for the study of the health of vegetarians in Asia are discussed. Vegetarian diets vary substantially, as may associated health outcomes. Cohort studies remain an important tool to better characterize the health of vegetarian populations around the globe.