Prediagnostic 25-Hydroxyvitamin D in Association with Cancer-specific and All-cause Mortality among Low-income, Non-Hispanic Black Americans with Colorectal Cancer.

BACKGROUND: Observational studies show high prediagnosis 25-hydroxyvitamin D is associated with lower mortality after colorectal cancer diagnosis. Results from clinical trials suggest vitamin D supplementation may improve outcomes among patients with colorectal cancer. Most studies included few Black Americans, who typically have lower 25-hydroxyvitamin D. We evaluated associations between serum 25-hydroxyvitamin D and mortality after colorectal cancer diagnosis among Black American cases. METHODS: Data arose from 218 Black Americans from the Southern Community Cohort Study diagnosed with colorectal cancer during follow-up (age 40-79 at enrollment). Prediagnostic 25-hydroxyvitamin D was measured at enrollment and categorized as deficient (<12 ng/mL), insufficient (12-19.9 ng/mL), or sufficient (≥20 ng/mL). Mortality was determined from the National Death Index. Cox proportional hazards were used to estimate HRs and 95% confidence intervals (CI) for associations between 25-hydroxyvitamin D and mortality. RESULTS: As a continuous exposure, higher 25-hydroxyvitamin D was associated with overall mortality [HR = 0.79 (0.65-0.96) per-SD increase, Ptrend = 0.02] and colorectal cancer-specific mortality [HR = 0.83 (0.64-1.08), Ptrend = 0.16]. For overall mortality, associations were strongest among females [HR = 0.65 (0.42-0.92)], current smokers [HR = 0.61 (0.38-0.98)], and obese participants [HR = 0.47 (0.29-0.77)]. Compared with those with deficiency, participants with sufficient 25-hydroxyvitamin D had lower overall mortality after multivariable adjustment [HR: 0.61 (0.37-1.01)]. CONCLUSIONS: Prediagnosis 25-hydroxyvitamin D is inversely associated with overall and colorectal cancer-specific mortality among Black Americans with colorectal cancer. Correcting vitamin D deficiency may improve survival of these patients, particularly for obese individuals and smokers. IMPACT: Our results support including more Black Americans in trials of vitamin D supplementations to improve colorectal cancer outcomes.

Tea Consumption and Gut Microbiome in Older Chinese Adults.

BACKGROUND: Animal and small-cohort human studies have shown that tea consumption affects the gut microbiome, but evidence from large cohort studies is lacking. OBJECTIVES: We examined associations between tea consumption and gut microbiome composition among older Chinese adults. METHODS: The study included 1179 men and 1078 women from the Shanghai Men's and Women's Health Studies, who reported tea drinking status, type, amount, and duration at baseline and follow-up surveys (1996-2017) and were free of cancer, cardiovascular disease, and diabetes at stool collection (2015-2018). Fecal microbiome was profiled using 16S rRNA sequencing. Associations of tea variables with microbiome diversity and taxa abundance were evaluated using linear or negative binomial hurdle models after adjusting for sociodemographics, lifestyle, and hypertension status. RESULTS: Mean age at stool collection was 67.2 ± 9.0 y in men and 69.6 ± 8.5 y in women. Tea drinking was not associated with microbiome ɑ-diversity in men or women; however, all tea variables were associated with ß-diversity in men (P < 0.001). Significant associations with taxa abundance were also observed mostly in men. Current tea drinking, mainly green tea drinking, was associated with increase in orders Synergistales and RF39 in men (ß = 0.30 to 0.42, all PFDR ≤ 0.10) but not in women (PInteraction-sex = 0.01). Also, increase in families Coriobacteriaceae, Odoribacteraceae, genera Collinsella, Odoribacter, and species Collinsella aerofaciens, Coprococcus catus, and Dorea formicigenerans were observed among men who drank >3.3 cups (781 mL)/d compared to that of nondrinkers (all PFDR <0.10). The increased Coprococcus catus related to tea drinking was more evident among men without hypertension and inversely associated with the prevalence of hypertension (OR: 0.90; 95% CI: 0.84, 0.97; PFDR = 0.03). CONCLUSIONS: Tea consumption may affect gut microbiome ß-diversity and abundance of some bacteria, which may contribute to reduced hypertension risk in Chinese men. Future studies should examine the sex-specific tea-gut microbiome associations and how certain bacteria may mediate the health benefits of tea.

Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies.

BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study.

BACKGROUND: Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk. OBJECTIVES: We evaluated the association of ginseng consumption with risk of total and 15 site-specific cancers in a large cohort study conducted among Chinese women. Given the previous literature on ginseng consumption and cancer risk, we hypothesized that ginseng consumption might be associated with varying risks of cancer. METHODS: This study included 65,732 female participants (mean age: 52.2 years) of the Shanghai Women's Health Study, an ongoing prospective cohort study. Baseline enrollment occurred between 1997 and 2000, and follow-up concluded on 31 December 2016. Ginseng use and covariates were assessed via an in-person interview conducted at the baseline recruitment. The cohort was followed for cancer incidence. Cox proportional hazard models were used to estimate HRs and 95% CIs for ginseng-cancer associations after adjusting for confounders. RESULTS: During a mean 14.7 years of follow-up, 5067 incident cancer cases were identified. Overall, regular ginseng use was mostly not associated with risk of any site-specific cancer, or all cancers combined. Short-term (<3 years) ginseng use was found to be significantly associated with increased risk of liver cancer (HR = 1.71; 95% CI: 1.04, 2.79; P = 0.035), whereas long-term (≥3 years) ginseng use was found to be associated with increased risk of thyroid cancer (HR = 1.40; 95% CI: 1.02, 1.91; P = 0.036). Long-term ginseng use was found to be significantly associated with decreased risk of lymphatic and hematopoietic tissue malignancy (HR = 0.67; 95% CI: 0.46, 0.98; P = 0.039) and non-Hodgkin's lymphoma (HR = 0.57; 95% CI: 0.34, 0.97; P = 0.039). CONCLUSIONS: This study provides suggestive evidence that ginseng consumption may be associated with risk of certain cancers.

Associations of Dietary Intakes of Carotenoids and Vitamin A with Lung Cancer Risk in a Low-Income Population in the Southeastern United States.

Observational studies found inverse associations of dietary carotenoids and vitamin A intakes with lung cancer risk. However, interventional trials among high-risk individuals showed that ß-carotene supplements increased lung cancer risk. Most of the previous studies were conducted among European descendants or Asians. We prospectively examined the associations of lung cancer risk with dietary intakes of carotenoids and vitamin A in the Southern Community Cohort Study, including 65,550 participants with 1204 incident lung cancer cases. Multivariate Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Lung cancer cases had lower energy-adjusted dietary intakes of all carotenoids and vitamin A than non-cases. However, dietary intakes of carotenoids and vitamin A were not associated with overall lung cancer risk. A significant positive association of dietary vitamin A intake with lung cancer risk was observed among current smokers (HRQ4 vs. Q1 = 1.23; 95% CI: 1.02-1.49; Ptrend = 0.01). In addition, vitamin A intake was associated with an increased risk of adenocarcinoma among African Americans (HRQ4 vs. Q1 = 1.55; 95%CI: 1.08-2.21; Ptrend = 0.03). Dietary lycopene intake was associated with an increased risk of lung cancer among former smokers (HRQ4 vs. Q1 = 1.50; 95% CI: 1.04-2.17; Ptrend = 0.03). There are positive associations of dietary ß-cryptoxanthin intake with squamous carcinoma risk (HRQ4 vs. Q1 = 1.49; 95% CI: 1.03-2.15; Ptrend = 0.03). Further studies are warranted to confirm our findings.

Association of Ginseng Consumption With All-cause and Cause-specific Mortality: Shanghai Women's Health Study.

BACKGROUND: Ginseng, an herbal remedy, has been commonly used in Asian countries to promote longevity and health for over 2,000 years. However, the association of ginseng consumption with all-cause and cause-specific mortality is still unclear. We analyzed the association of total and major cause-specific mortality (cardiovascular disease [CVD], cancer, and other death) with consumption of ginseng (primarily American and white ginseng). METHODS: This study included 56,183 female participants with an average follow-up of 14.7 years in the Shanghai Women's Health Study, an ongoing prospective cohort study. Data were assessed via an in-person interview conducted at baseline recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ginseng-mortality associations after adjusting for confounders. RESULTS: Compared with those who never used ginseng, regular ginseng use was associated with significantly reduced all-cause mortality (HR 0.92; 95% CI, 0.87-0.98). This inverse association was seen primarily among those who consumed ginseng for perceived general health benefit (HR 0.90; 95% CI, 0.85-0.96). A significant dose-response association was observed between duration of ginseng use and total mortality (HR 0.85, for using ≥6 years vs never use; P for trend <0.001), CVD mortality (HR 0.83; P for trend = 0.019), and other-cause mortality (HR 0.76; P for trend = 0.001). However, no dose-response association was observed between amount of ginseng consumption and mortality outcomes. CONCLUSION: Regular ginseng consumption, particularly over a long duration, was associated with decreased risk of all causes of death, death due to CVD, and death due to certain other diseases.

Phytoestrogens and lung cancer risk: a nested case-control study in never-smoking Chinese women.

BACKGROUND: Since several lines of evidence suggest that estrogens may be involved in lung carcinogenesis, it has been hypothesized that intake of phytoestrogens, similar in molecular structure to mammalian estrogens, may be associated with lung cancer development. OBJECTIVE: The aim was to prospectively evaluate the association between phytoestrogen exposure and lung cancer risk in never-smoking women. METHODS: We conducted a nested case-control study within a population-based prospective cohort study of women. A total of 478 incident lung cancer cases and their individually matched controls were identified among never-smoking women after a mean follow-up of 15.6 years. Habitual intake of and internal exposure to phytoestrogens were assessed by repeated dietary surveys and urinary biomarkers, respectively. ORs and 95% CIs for lung cancer were estimated in conditional logistic regression models. RESULTS: After adjustment for potential confounders, a moderate intake of dietary isoflavones was inversely associated with lung cancer risk in never-smoking women, with the OR for the second quartile vs. the lowest quartile of intake being 0.52 (95% CI: 0.35, 0.76). Further increasing intake did not convey additional benefits, with ORs (95% CI) for the third and fourth quartiles of 0.53 (0.36, 0.78) and 0.47 (0.31, 0.72), respectively (P-overall < 0.001 and P-nonlinearity = 0.006). A similar association was seen when exposure to isoflavones was assessed by urinary biomarkers. ORs (95% CI) for the second, third, and fourth quartiles compared with the lowest quartile of urinary isoflavone excretion were 0.57 (0.39, 0.83), 0.64 (0.44, 0.92), and 0.60 (0.41, 0.86), respectively. The inverse association reached a plateau beyond the second quartile, with P-overall = 0.04 and P-nonlinearity = 0.15. Urinary excretion of gut-microbiota-derived metabolites of lignans was not related to lung cancer risk. CONCLUSIONS: This study suggests that moderately increasing intake of isoflavone-rich foods is associated with lower risk of lung cancer in never-smoking women.

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Association between Tea Consumption and Hypertension Risk among Middle-Aged and Older Chinese Adults.

BACKGROUND: Current evidence on tea consumption and hypertension is inconclusive, and prospective studies among habitual tea drinkers remain limited. OBJECTIVE: We investigated the associations of habitual tea consumption with hypertension risk and longitudinal blood pressure changes in 2 large cohorts. METHODS: This study included participants aged 40-75 y from the Shanghai Women's Health Study (n = 31,351) and the Shanghai Men's Health Study (n = 28,342), without hypertension, diabetes, cardiovascular disease, or cancer at baseline. Information on tea consumption was assessed during in-person interviews at enrollment and follow-up visits. Incident hypertension was identified by self-reported diagnosis, medication use, or blood pressure measurements. RESULTS: Current tea drinkers had a 7% higher risk than the non-current tea drinker group [HRs (95% CIs): women, 1.07 (1.01, 1.14); men, 1.07 (1.02, 1.12)]. The amount of tea drinking showed significant dose-response associations with hypertension: compared with the non-current group, HRs (95% CIs) for women and men were 1.01 (0.90, 1.14) and 1.02 (0.96, 1.08) for low (women/men: <100/200 g/mo), 1.07 (1.01, 1.15) and 1.05 (0.99, 1.12) for medium (women/men: 100-250/200-250 g/mo), and 1.18 (1.01, 1.39) and 1.10 (1.03, 1.17) for the high-amount group (women/men: >250 g/mo). Among participants without hypertension, compared with non-current tea drinkers, least-squares means of 3-y changes in blood pressure were 0.3-0.4 mm Hg higher for women and men as current drinkers and 0.7-0.9 mm Hg higher for men in the high-consumption group. Compared with those who never drank tea, women who drank tea consistently had 0.5 (0.2, 0.7) mm Hg higher diastolic blood pressure (DBP), whereas men had 0.5 (0.04, 0.9) mm Hg higher systolic blood pressure and 0.3 (0.04, 0.6) mm Hg higher DBP, respectively. CONCLUSIONS: Our findings suggest that habitual tea drinking is associated with a slightly higher risk of hypertension and a minor increase in blood pressure among middle-aged and older Chinese adults, which warrants confirmation by long-term intervention studies.

Outcomes After Use of a Lymph Node Collection Kit for Lung Cancer Surgery: A Pragmatic, Population-Based, Multi-Institutional, Staggered Implementation Study.

INTRODUCTION: Suboptimal pathologic nodal staging prevails after curative-intent resection of lung cancer. We evaluated the impact of a lymph node specimen collection kit on lung cancer surgery outcomes in a prospective, population-based, staggered implementation study. METHODS: From January 1, 2014, to August 28, 2018, we implemented the kit in three homogeneous institutional cohorts involving 11 eligible hospitals from four contiguous hospital referral regions. Our primary outcome was pathologic nodal staging quality, defined by the following evidence-based measures: the number of lymph nodes or stations examined, proportions with poor-quality markers such as nonexamination of lymph nodes, and aggregate quality benchmarks including the National Comprehensive Cancer Network criteria. Additional outcomes included perioperative complications, health care utilization, and overall survival. RESULTS: Of 1492 participants, 56% had resection with the kit and 44% without. Pathologic nodal staging quality was significantly higher in the kit cases: 0.2% of kit cases versus 9.8% of nonkit cases had no lymph nodes examined; 3.2% versus 25.3% had no mediastinal lymph nodes; 75% versus 26% attained the National Comprehensive Cancer Network criteria (p < 0.0001 for all comparisons). Kit cases revealed no difference in perioperative complications or health care utilization except for significantly shorter duration of surgery, lower proportions with atelectasis, and slightly higher use of blood transfusion. Resection with the kit was associated with a lower hazard of death (crude, 0.78 [95% confidence interval: 0.61-0.99]; adjusted 0.85 [0.71-1.02]). CONCLUSIONS: Lung cancer surgery with a lymph node collection kit significantly improved pathologic nodal staging quality, with a trend toward survival improvement, without excessive perioperative morbidity or mortality.

Dietary fatty acids and colorectal cancer risk in men: A report from the Shanghai Men's Health Study and a meta-analysis.

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; Ptrend = 0.47) for SFA, 0.95 (0.79-1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95-1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.

Adherence to treatment guidelines as a major determinant of survival disparities between black and white patients with ovarian cancer.

OBJECTIVE: To evaluate whether non-adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and other factors related to treatment access contribute to racial disparities in ovarian cancer survival. METHODS: This large cohort study included patients from the National Cancer Database who were diagnosed with ovarian cancer between 2004 and 2014, with follow-up data up to 2017. The multivariable Cox regression was used to assess the effect of study variables on five-year overall survival. The proportion contributions of prognostic factors to the survival disparities were estimated using individual and sequential adjustment of these factors based on the Cox proportional hazards models. RESULTS: Of the 120,712 patients eligible for this study, 110,032 (91.1%) were whites and 10,680 (8.9%) were blacks. Black patients, compared with their white counterparts, had a lower adherence to NCCN guidelines (60.8% vs. 70.4%, respectively, P < 0.001), and a higher five-year mortality after cancer diagnosis (age- and tumor characteristics- adjusted hazard ratio: 1.22, 95% confidence interval: 1.19-1.25). Non-adherence to NCCN treatment guidelines was the most significant contributor to racial disparity in ovarian cancer survival, followed by access to care and comorbidity, each explaining 36.4%, 22.7%, and 18.2% of the racial differences in five-year overall survival, respectively. These factors combined explain 59.1% of racial survival disparities. Risk factors identified for non-adherence to treatment guidelines among blacks include insurance status, treatment facility type, educational attainment, age, and comorbidity. CONCLUSIONS: Adherence status to NCCN treatment guidelines is the most important contributor to the survival disparities between black and white patients with ovarian cancer. Our findings call for measures to promote equitable access to guideline-adherence care to improve the survival of black women with ovarian cancer.

Evaluation of determinants for age disparities in the survival improvement of colon cancer: results from a cohort of more than 486,000 patients in the United States.

Over the past two decades, elderly colon cancer patients experienced less improvement in survival than their younger counterparts, yet the contributing factors remain unknown. We aimed to evaluate factors that may contribute to the age disparity of survival improvement among patients with colon cancer. Using data from the National Cancer Database, we identified patients diagnosed with colon cancer between 2004 and 2012 with follow-up data up to 2017. The hazard ratios (HR) and 95% confidence intervals (CI) for 5-year OS associated with study variables were estimated using multivariable Cox regression. Among 486,284 patients included in this study, elderly patients (aged ≥75) had a lower adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines (% of non-adherence: 45.3%) than younger patients (aged <50, 19.3%; P<0.001). After adjusting for demographics, access to care and clinical characteristics, compared with patients diagnosed between 2004 and 2006, younger and older patients diagnosed between 2010 and 2012 experienced 16% (HR: 0.84, 95% CI: 0.81-0.88) and 6% (HR: 0.94, 95% CI: 0.93-0.95) reductions in mortality (P for interaction=1.42×10-5), respectively. After an additional adjustment for guideline adherence status, no significant difference in the improvement of survival was noted (P for interaction=0.17). The association patterns were similar regardless of tumor stage, race, and high comorbidity scores (all P for interaction>0.05). Several patient-related factors were identified in association with noncompliance to NCCN guidelines, including comorbidity status. However, over 60% of noncompliance elderly patients had a Charlson comorbidity score of 0. The observed age disparity in survival improvement among colon cancer patients was primarily explained by a slower improvement in adherence to NCCN treatment guidelines in elderly than younger patients. Many older adults were not receiving recommended therapies despite minimal comorbidities. Our findings call for measures to increase adherence to treatment guidelines among elderly patients to improve survival.

Food intake of folate, folic acid and other B vitamins with lung cancer risk in a low-income population in the Southeastern United States.

PURPOSE: We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US. METHODS: Within the Southern Community Cohort Study, we included 1064 incident lung cancer cases among 68,236 participants aged 40-79 years at study enrollment. Food intake and the use of folic acid-containing supplements were assessed using a validated food frequency questionnaire at study enrollment. Multivariate Cox regression was used to estimate hazards ratios (HRs) and the 95% confidence intervals (CIs). RESULTS: Folate and/or folic acid intake from food were not associated with lung cancer risk; HRs (95% CI) for highest compared with lowest quartile were 1.08 (0.91-1.29) for total dietary folate, 1.00 (0.84-1.19) for food folate, and 1.09 (0.91-1.30) for food folic acid, respectively. Similarly, no associations were observed after stratifying by sex, race and smoking status, except for a positive association with total dietary folate intake among black women (HR 1.46, 95% CI 1.04-2.05 for the highest quartile compared with the lowest quartile, P trend = 0.02). Neither the use of folic acid-containing supplements nor food intake of vitamin B6, vitamin B12 and riboflavin were associated with lung cancer risk. CONCLUSIONS: Our findings do not support a protective effect of folate or folic acid for lung cancer prevention in a low-income population of black and white adults in the Southeastern US. Our finding of a positive association with total dietary folate intake among black women needs to be interpreted with caution and replicated in other studies.

Adherence to dietary recommendations and colorectal cancer risk: results from two prospective cohort studies.

BACKGROUND: Understanding the association between diet and colorectal cancer (CRC) risk is essential to curbing the epidemic of this cancer. This study prospectively evaluated adherence to the Chinese Food Pagoda (CHFP), and two American Dietary Guidelines: the Alternative Healthy Eating Index (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) in association with CRC risk among Chinese adults living in urban Shanghai, China. METHODS: Participants included 60 161 men and 72 445 women aged 40-74, from two ongoing population-based prospective cohort studies. Associations between dietary guideline compliance scores and CRC risk were evaluated by Cox proportional hazard regression analyses, with age as time metric, and potential confounders were adjusted. RESULTS: We identified 1670 CRC incidence cases (691 males and 979 females) during an average 8.1 years of follow-up for men and 13.4 years for women. CHFP score was inversely associated with risk of CRC, with hazard ratios (HRs) (95% confidence intervals) of 0.88 (0.77, 1.00), 0.86 (0.75, 0.98) and 0.84 (0.73, 0.96) for the 2nd, 3rd and 4th quartiles versus 1st quartile, respectively (Ptrend= 0.01). The inverse association appeared stronger for rectal cancer, individuals at younger age (< 50 years), with a lower BMI (<25 kg/m2) or without any metabolic conditions at baseline, although no multiplicative interactions were noted. No consistent association pattern was observed for the modified DASH score and the modified AHEI-2010. CONCLUSIONS: Compliance with the Dietary Guidelines for Chinese was associated with reduced risk of CRC among Chinese adults. To maximize health impacts, dietary recommendations need to be tailored for specific populations.

Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

Transcriptome-Wide Association Study Identifies Susceptibility Loci and Genes for Age at Natural Menopause.

OBJECTIVE: To identify novel susceptibility genes for age at natural menopause (ANM). METHODS: Using transcription data generated in tissues from normal hypothalami (n = 73) and ovaries (n = 68) and high-density genotyping data provided by the Genotype-Tissue Expression (GTEx) database, we built 16 164 genetic models to predict gene expression across the transcriptome in these tissues. We used these models and summary statistics data from genome-wide association studies (GWAS) of ANM generated in 69 360 women of European ancestry to identify genes with their predicted expression related to ANM. RESULTS: We found the predicted expression of 34 genes to be significantly associated with ANM at a Bonferroni-corrected threshold of P < 3.09 ×10-6. These include 4 genes located more than 1 Mb away from any previously GWAS-identified ANM-associated variants, 24 genes that reside in known GWAS-identified loci but have not been previously implicated, and 6 genes previously implicated as ANM-associated genes. CONCLUSION: Results from this transcriptome-wide association study, which integrated Expression quantitative trait loci (eQTL) data with summary statistics of GWAS of ANM, improves our understanding of the genetics and biology of female reproductive aging.

Green tea intake and risk of incident kidney stones: Prospective cohort studies in middle-aged and elderly Chinese individuals.

OBJECTIVES: To investigate the association between green tea intake and incident stones in two large prospective cohorts. METHODS: We examined self-reported incident kidney stone risk in the Shanghai Men's Health Study (n = 58 054; baseline age 40-74 years) and the Shanghai Women's Health Study (n = 69 166; baseline age 40-70 years). Information on the stone history and tea intake was collected by in-person surveys. Multivariable Cox proportional hazards models were adjusted for baseline demographic variables, medical history and dietary intakes including non-tea oxalate from a validated food frequency questionnaire. RESULTS: During 319 211 and 696 950 person-years of follow up, respectively, 1202 men and 1451 women reported incident stones. Approximately two-thirds of men and one-quarter of women were tea drinkers at baseline, of whom green tea was the primary type consumed (95% in men, 88% in women). Tea drinkers (men: hazard ratio 0.78, 95% confidence interval 0.69-0.88; women: hazard ratio 0.8, 95% confidence interval 0.77-0.98) and specifically green tea drinkers (men: hazard ratio 0.78, 95% confidence interval 0.69-0.88; women: hazard ratio 0.84, 95% confidence interval 0.74-0.95) had lower incident risk than never/former drinkers. Compared with never/former drinkers, a stronger dose-response trend was observed for the amount of dried tea leaf consumed/month by men (hazard ratiohighest category 0.67, 95% confidence interval 0.56-0.80, Ptrend  < 0.001) than by women (hazard ratiohighest category 0.87, 95% confidence interval 0.70-1.08, Ptrend  = 0.041). CONCLUSIONS: Green tea intake is associated with a lower risk of incident kidney stones, and the benefit is observed more strongly among men.

Green tea consumption and risk of type 2 diabetes in Chinese adults: the Shanghai Women's Health Study and the Shanghai Men's Health Study.

Background: Epidemiological evidence on the association between tea consumption and the risk of type 2 diabetes (T2D) is inconsistent. This study prospectively investigated whether green tea drinking affects the risk of T2D. Methods: This study included participants from the Shanghai Women's Health Study (N = 67 058) and the Shanghai Men's Health Study (N = 52 315) without diabetes at study enrolment. Details of tea consumption, including types and amounts, were collected at the baseline and follow-up survey. Incident T2D was identified through follow-up surveys. Plasma level of caffeine metabolite was measured in a nested case-control study involving 592 diabetes case-control pairs. Cox regression analysis, with tea drinking as a time-dependent variable and covariates adjusted for by a propensity score, was applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) for T2D risk. Logistic regression analysis was applied to evaluate the association between caffeine metabolites and T2D risk. Results: Current green tea drinkers had an increased risk of T2D compared with non-current drinkers [HR = 1.20 (95% CI = 1.14-1.27)], and a dose-response relationship was observed for duration of drinking tea and the amount of tea consumed [P for trend <0.001]. The increased risk associated with green tea drinking was observed in both women and men, across the entire period of follow-up, with HR (95% CI) of 1.08 (0.97-1.19) within 5 years of follow-up, 1.22 (1.12-1.32) during the period of 5-10 years of follow-up and 1.16 (1.03-1.30) after 10 years of follow-up. This association did not vary significantly by body mass index, waist-to-hip circumference ratio or smoking status. Plasma level of caffeine was also associated with increased diabetes risk (P = 0.03), confirming the results based on self-reported tea drinking. Conclusions: Green tea drinking was associated with an increased risk of T2D in Chinese adults. The mechanisms underlying the association need to be elucidated.