Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

BACKGROUND: Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. METHODS: In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. RESULTS: During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 µmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. CONCLUSIONS: Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Impact of a one-year supervised physical activity program on long-term cancer-related fatigue and mediating effects of the gut microbiota in metastatic testicular cancer patients: protocol of the prospective multicentre, randomized controlled phase-III STARTER trial.

BACKGROUND: Testicular germ cell tumours (TGCTs) are the most common malignancy in men aged 15-40 years, with increasing incidence worldwide. About 33 ~ 50% of the patients present with metastatic disease at diagnosis. TGCT survivors experience short- and long-term sequelae, including cancer-related fatigue (CRF). Physical activity (PA) has established effects on reducing CRF and other sequelae and improving health-related quality of life (HRQoL). However, its impact on TGCT survivors has so far received little attention. The gut microbiota plays a crucial role in various physiological functions, including cognition and metabolism, and may mediate the effects of PA on CRF and other sequelae, but this has not been investigated in randomized controlled trials. METHODS: This national, multicentre, phase-III trial will evaluate the impact of a one-year supervised PA program on CRF and other short- and long-term sequelae in metastatic TGCT patients receiving cisplatin-based chemotherapy combined with etoposide+/-bleomycin. It will also investigate potential mediating effects of the gut microbiota and its metabolites involved in the gut-brain axis on the relationship between PA and CRF and other sequelae. A total of 236 men ≥ 18 years of age with metastatic TGCT (seminoma and non-seminoma) will be enrolled before starting first-line chemotherapy in several French hospitals. The primary (CRF) and secondary (cognitive/psychological/metabolic sequelae, HRQoL, etc.) outcomes and gut microbiota and relevant metabolites will be assessed at inclusion, during and at the end of the one-year intervention, and annually until 10 years since inclusion to assess long-term sequelae, more specifically CRF, cardiovascular toxicities, and second primary cancer occurrence in this population. DISCUSSION: This trial will provide comprehensive and novel insights into the effects of a long-term supervised PA program on CRF and other sequelae in metastatic TGCT patients receiving first-line chemotherapy. It will also contribute to understanding the potential role of the gut microbiota and its metabolites in mediating the effects of PA on these outcomes. The findings of this study will help the development of effective PA interventions to improve the health of TGCT survivors and may have implications for other cancer populations as well. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT05588700) on 20 Oct. 2022.

Association of a dietary pattern related to serum vitamin D levels with metabolic syndrome risk among Korean adults: based on the Korean national health and nutrition examination survey.

PURPOSE: Vitamin D has a crucial role in our metabolic health. We aimed to examine associations of vitamin D status and its related dietary pattern (DP) with prevalent risk of metabolic syndrome (MetS) in 9,237 Korean adults aged 19-64 years based on the National Health and Nutrition Examination Survey. METHODS: Vitamin D status was examined by serum 25-hydroxyvitamin D (25(OH)D). A vitamin D-related DP associated with 25(OH)D levels was derived using reduced rank regression (RRR). Associations of vitamin D status and its related DP with MetS prevalence were examined using multivariable logistic regression models adjusted for potential confounders. RESULTS: Men with sufficient vitamin D status had a 44% lower risk of MetS prevalence (OR: 0.56; 95%CI: 0.36-0.87) compared to those with deficiency. A vitamin D-related DP derived using RRR was characterized by high intakes of vegetables, fish, fruits, and nuts and low intakes of eggs, oils, and mushrooms in this study population. Among men, the DP was significantly associated with a lower risk of MetS prevalence, showing a 12% (95%CI: 4-20%) reduction in risk for a one-unit increase in the DP score. However, there was no significant association among women. CONCLUSION: The study's findings suggest that a sufficient vitamin D status and a related DP with high intakes of vegetables, fish, fruit, and nuts were associated with the risk of MetS, particularly in Korean male adults.

Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population-based study in Icelandic women.

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m2 per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04-1.13), 1.31 (95% CI: 1.18-1.44) and 1.10 (95% CI: 1.00-1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity-cancer relationships.

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.

A prospective evaluation of plasma polyphenol levels and colon cancer risk.

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; qvalue = 0.01) and homovanillic acid (OR per log2 -value, 1.46, 95% CI = 1.16-1.84; qvalue = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, ptrend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, ptrend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.

Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study.

PURPOSE: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. METHODS: This study includes 373,293 men and women, 25-70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). RESULTS: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (-0.07 kg; 95% CI -0.12 to -0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92-0.98) or obese (RR 0.95; 95% CI 0.90-0.99) (both P trend <0.008). CONCLUSIONS: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.

Evaluation of urinary resveratrol as a biomarker of dietary resveratrol intake in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

In vitro studies have shown several beneficial properties of resveratrol. Epidemiological evidence is still scarce, probably because of the difficulty in estimating resveratrol exposure accurately. The current study aimed to assess the relationships between acute and habitual dietary resveratrol and wine intake and urinary resveratrol excretion in a European population. A stratified random subsample of 475 men and women from four countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study, who had provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day, were included. Acute and habitual dietary data were collected using standardised 24-HDR software and a validated country-specific dietary questionnaire, respectively. Phenol-Explorer was used to estimate the intake of resveratrol and other stilbenes. Urinary resveratrol was analysed using tandem MS. Spearman's correlation coefficients between estimated dietary intakes of resveratrol and other stilbenes and consumption of wine, their main food source, were very high (r>0·9) when measured using dietary questionnaires and were slightly lower with 24-HDR (r>0·8). Partial Spearman's correlations between urinary resveratrol excretion and intake of resveratrol, total stilbenes or wine were found to be higher when using the 24-HDR (R 2 partial approximately 0·6) than when using the dietary questionnaires (R 2 partial approximately 0·5). Moderate to high correlations between dietary resveratrol, total stilbenes and wine, and urinary resveratrol concentrations were observed. These support the earlier findings that 24-h urinary resveratrol is an effective biomarker of both resveratrol and wine intakes. These correlations also support the validity of the estimation of resveratrol intake using the dietary questionnaire and Phenol-Explorer.

Multi-Trait Body Shape Phenotypes and Breast Cancer Risk in Postmenopausal Women: A Causal Mediation Analysis in the UK Biobank Cohort.

Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.

Inhibitory effect of a Cirsium setidens extract on hepatic fat accumulation in mice fed a high-fat diet via the induction of fatty acid ß-oxidation.

Cirsium setidens is a perennial medicinal herb that is rich in flavonoids. We investigated in this study the effect of a C. setidens ethanol extract (CSE) on the development of nonalcoholic fatty liver in mice fed a high-fat diet (HF). C57BL/6J mice were fed either a control diet (CON) or HF for 8 weeks, and then fed CON, HF, or HF with 100 mg/kg of BW CSE (HF+CSE) for an additional 7 weeks. The final body weight and adipose tissue weight of the mice in the HF+CSE group were significantly lower than those in the HF group. CSE also markedly diminished both the lipid droplets in the liver tissues and decreased the hepatic and serum triglycerides (TG) concentrations. CSE strongly increased the hepatic mRNA levels of carnitine palmitoyltransferase (CPT1) and medium-chain acyl-CoA dehydrogenase (MCAD), the fatty acid ß-oxidation enzymes. The hepatic levels of phosphorylated-AMP-activated protein kinase (AMPK) were significantly higher in the HF+CSF group than in the HF group. These results suggest that CSE inhibited hepatic fat accumulation by up-regulating the expression of the fatty acid ß-oxidation genes.

Dried Fruits, Nuts, and Cancer Risk and Survival: A Review of the Evidence and Future Research Directions.

Dried fruits and nuts contain high amounts of nutrients and phytochemicals-all of which may have anticarcinogenic, anti-inflammatory, and antioxidant properties. This narrative review summarizes the evidence for dried fruits and nuts and cancer incidence, mortality, and survival and their potential anticancer properties. The evidence for dried fruits in cancer outcomes is limited, but existing studies have suggested an inverse relationship between total dried fruit consumption and cancer risk. A higher consumption of nuts has been associated with a reduced risk of several site-specific cancers in prospective cohort studies, including cancers of the colon, lung, and pancreas, with relative risks per 5 g/day increment equal to 0.75 (95% CI 0.60, 0.94), 0.97 (95% CI 0.95, 0.98), and 0.94 (95% CI 0.89, 0.99), respectively. A daily intake of total nuts of 28 g/day has also been associated with a 21% reduction in the rate of cancer mortality. There is also some evidence that frequent nut consumption is associated with improved survival outcomes among patients with colorectal, breast, and prostate cancer; however, further studies are needed. Future research directions include the investigation of additional cancer types, including rare types of cancer. For cancer prognosis, additional studies with pre- and postdiagnosis dietary assessment are warranted.

Differences in dietary patterns related to metabolic health by gut microbial enterotypes of Korean adults.

Diet has a profound impact on the progression of metabolic syndrome (MetS) into various diseases. The gut microbiota could modulate the effect of diet on metabolic health. We examined whether dietary patterns related to MetS differed according to gut microbial enterotypes among 348 Korean adults aged 18-60 years recruited between 2018∼2021 in a cross-sectional study. The enterotype of each participant was identified based on 16S rRNA gut microbiota data. The main dietary pattern predicting MetS (MetS-DP) of each enterotype was derived using reduced-rank regression (RRR) models. In the RRR models, 27 food group intakes assessed by a semi-quantitative food frequency questionnaire and MetS prediction markers including triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) were used as predictor and response variables, respectively. The MetS-DP extracted in Bacteroides enterotype (B-type) was characterized by high consumption of refined white rice and low consumption of eggs, vegetables, and mushrooms. The MetS-DP derived among Prevotella enterotype (P-type) was characterized by a high intake of sugary food and low intakes of bread, fermented legumes, and fermented vegetables. The MetS-DP of B-type was positively associated with metabolic unhealthy status (OR T3 vs. T1 = 3.5; 95% CI = 1.5-8.2), comparing the highest tertile to the lowest tertile. Although it was not significantly associated with overall metabolic unhealthy status, the MetS-DP of P-type was positively associated with hyperglycemia risk (OR T3 vs. T1 = 6.2; 95% CI = 1.6-24.3). These results suggest that MetS-DP may differ according to the gut microbial enterotype of each individual. If such associations are found to be causal, personalized nutrition guidelines based on the enterotypes could be recommended to prevent MetS.

Excess Body Fatness during Early to Mid-Adulthood and Survival from Colorectal and Breast Cancer: A Pooled Analysis of Five International Cohort Studies.

BACKGROUND: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries. METHODS: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis. RESULTS: We found a significant dose-response relationship (P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer. CONCLUSIONS: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer. IMPACT: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.

Taxonomic Composition and Diversity of the Gut Microbiota in Relation to Habitual Dietary Intake in Korean Adults.

We investigated associations of habitual dietary intake with the taxonomic composition and diversity of the human gut microbiota in 222 Koreans aged 18-58 years in a cross-sectional study. Gut microbiota data were obtained by 16S rRNA gene sequencing on DNA extracted from fecal samples. The habitual diet for the previous year was assessed by a food frequency questionnaire. After multivariable adjustment, intake of several food groups including vegetables, fermented legumes, legumes, dairy products, processed meat, and non-alcoholic beverages were associated with major phyla of the gut microbiota. A dietary pattern related to higher α-diversity (HiαDP) derived by reduced rank regression was characterized by higher intakes of fermented legumes, vegetables, seaweeds, and nuts/seeds and lower intakes of non-alcoholic beverages. The HiαDP was positively associated with several genera of Firmicutes such as Lactobacillus, Ruminococcus, and Eubacterium (all p < 0.05). Among enterotypes identified by principal coordinate analysis based on the ß-diversity, the Ruminococcus enterotype had higher HiαDP scores and was strongly positively associated with intakes of vegetables, seaweeds, and nuts/seeds, compared to the two other enterotypes. We conclude that a plant- and fermented food-based diet was positively associated with some genera of Firmicutes (e.g., Lactobacillus, Ruminococcus, and Eubacterium) reflecting better gut microbial health.

Metabolic tracking of isoflavones in soybean products and biosamples from healthy adults after fermented soybean consumption.

Fermentation may enhance the nutritional properties of foods by increasing metabolite bioactivity or bioavailability. This study explored the effect of fermentation on isoflavone bioavailability and metabolism. Isoflavone metabolites were tracked in foods and biospecimens of healthy adults after fermented soybean (FS) or non-fermented soybean (NFS) consumption in a randomized, controlled, crossover intervention study. The change in soybean isoflavones caused by fermentation resulted in faster absorption and higher bioavailability after consumption of FS. Although the urinary level of total isoflavone metabolites was similar after the consumption of the two diets, urinary genistein 7-O-sulfate was derived as a discriminant metabolite for the FS diet by partial least squares discriminant analysis. This study suggests that an isoflavone conjugate profile might be a more appropriate marker than total isoflavone levels for discriminating between the consumption of FS and NFS diets.

A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.

Association between Urinary Cadmium to Zinc Intake Ratio with Adult Mortality in a Follow-Up Study of NHANES 1988-1994 and 1999-2004.

Cadmium (Cd) is a toxic heavy metal associated with increased mortality, but the effect of zinc (Zn) intake on the association between Cd and mortality is unknown. The objective of this study was to examine the association of urinary Cd to Zn intake ratio (Cd/Zn ratio) and mortality risk. In total, 15642 US adults in NHANES 1988-1994 and 1999-2004 were followed until 2011 (15-year mean follow-up). Of the 5367 total deaths, 1194 were attributed to cancer and 1677 were attributed to CVD. After adjustment for potential confounders, positive associations were observed between urinary Cd and all-cause mortality (HR for highest vs. lowest quartile: 1.38; 95% CI: 1.14-1.68) and cancer mortality (HR: 1.54; CI: 1.05-2.27). Urinary Cd was positively associated with cancer mortality among the lowest Zn consumers, and the association diminished among the highest Zn consumers. Positive relationships were observed between the Cd/Zn ratio and all-cause mortality (HR: 1.54; CI: 1.23-1.93), cancer mortality (HR: 1.65; CI: 1.11-2.47) and CVD mortality (HR: 1.49; CI: 1.18-1.88). In conclusion, these findings indicate that Zn intake may modify the association between Cd and mortality. Furthermore, the Cd/Zn ratio, which was positively associated with mortality from all causes, cancer, and CVD, may be an important predictor of mortality.

Adult Overweight and Survival from Breast and Colorectal Cancer in Swedish Women.

BACKGROUND: The impact of overweight duration and intensity during adulthood on the prognosis after a cancer diagnosis remains largely unknown. We investigated this association in Swedish women with breast and colorectal cancer. METHODS: A cohort of 47,051 women from the Swedish Lifestyle and Health Study was included, of whom 1,241 developed postmenopausal breast (mean age at diagnosis, 57.5 years) and 259 colorectal (mean age at diagnosis, 59.1 years) cancer. Trajectories of body mass index (BMI) between ages 20 and 50 years were estimated for the full cohort using a quadratic growth model and studied in relation to risk of death from any cause using multivariate Cox regression models among cancer survivors. RESULTS: Compared with patients with cancer who were never overweight (BMI < 25) during early adulthood (ages 20-50 years), the risk of early death from breast cancer increased by 3% [hazard ratio (HR) = 1.03; 95% confidence interval (CI), 1.01-1.05] and from colorectal cancer by 4% (HR = 1.04; 95% CI, 1.01-1.06) for every year lived with overweight. A higher intensity of overweight (i.e., a combination of duration and degree of overweight-a concept comparable to pack-years of cigarette smoking) further increased the risk of dying in this population. Although risks were slightly more pronounced for women diagnosed with late-stage breast cancer, no clear association was found for colorectal cancer. CONCLUSIONS: Our results suggest that adulthood overweight duration and intensity have a long-lasting influence on breast and colorectal cancer survival. IMPACT: Our study highlights the need for effective prevention of overweight and obesity starting at an early age.

The relationship between zinc intake and cadmium burden is influenced by smoking status.

A preliminary study by our group suggested that the absorption and accumulation of cadmium may be affected by zinc intake. Tobacco smoke is one major source of cadmium exposure that highly influences cadmium burden among smokers, but it is unclear whether this zinc-cadmium relationship differs by smoking status. The objective of this study was to examine whether the association between zinc intake and cadmium burden differs by smoking status using data from 3900 US adults in the National Health and Nutrition Examination Survey 2007-2012. In an adjusted regression model, dietary cadmium was positively associated with blood and urinary cadmium. There was a significant interaction between zinc intake and smoking status, so we analyzed associations within smoking status subgroups. In an adjusted regression model, zinc intake was inversely associated with urinary cadmium only among non-smokers. Failure to meet the Recommended Dietary Allowance (RDA) for zinc was more common among current smokers than non-smokers, and among those in the highest quintile of blood and urinary cadmium than those in lower quintiles. Zinc intake was inversely associated with urinary cadmium only among subjects meeting the zinc RDA, suggesting that the relationship between zinc intake and cadmium burden differs by smoking status.

Dietary Cadmium Intake and Sources in the US.

Cadmium (Cd) is a toxic heavy metal that can contribute to numerous diseases as well as increased mortality. Diet is the primary source of Cd exposure for most individuals, yet little is known about the foods and food groups that contribute most substantially to dietary Cd intake in the US. Therefore, the objective of this study was to estimate dietary Cd intake and identify major food sources of Cd in the US population and among subgroups of the population. Individuals aged 2 years and older from the National Health and Nutrition Examination Survey (NHANES) 2007⁻2012 were included in this study (n = 12,523). Cd intakes were estimated from two days of 24-h dietary recalls by matching intake data with the Cd database of the Food and Drug Administration (FDA)'s Total Diet Study 2006 through 2013. The average dietary Cd consumption in the population was 4.63 µg/day, or 0.54 µg/kg body weight/week, which is 22% of the tolerable weekly intake (TWI) of 2.5 µg/kg body weight/week. Greater daily Cd intakes were observed in older adults, males, those with higher income, higher education, or higher body mass index. The highest Cd intakes on a body weight basis were observed in children 10 years and younger (38% of TWI), underweight individuals (38% of TWI), and alcohol non-consumers (24% of TWI). The food groups that contributed most to Cd intake were cereals and bread (34%), leafy vegetables (20%), potatoes (11%), legumes and nuts (7%), and stem/root vegetables (6%). The foods that contributed most to total Cd intake were lettuce (14%), spaghetti (8%), bread (7%), and potatoes (6%). Lettuce was the major Cd source for Caucasians and Blacks, whereas tortillas were the top source for Hispanics, and rice was the top contributor among other ethnic subgroups including Asians. This study provides important information on the dietary Cd exposure of Americans, and identifies the groups with the greatest dietary Cd exposure as well as the major sources of dietary Cd among sociodemographic subgroups.