Standard Deviation Increment Research Articles

Systemic inflammation markers and cancer incidence in the UK Biobank

Systemic inflammation markers have been linked to increased cancer risk and mortality in a number of studies. However, few studies have estimated pre-diagnostic associations of systemic inflammation markers and cancer risk. Such markers could serve as biomarkers of cancer risk and aid in earlier identification of the disease. This study estimated associations between pre-diagnostic systemic inflammation markers and cancer risk in the prospective UK Biobank cohort of approximately 440,000 participants recruited between 2006 and 2010. We assessed associations between four immune-related markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for 17 cancer sites by estimating hazard ratios (HR) using flexible parametric survival models. We observed positive associations with risk for seven out of 17 cancers with SII, NLR, PLR, and negative associations with LMR. The strongest associations were observed for SII for colorectal and lung cancer risk, with associations increasing in magnitude for cases diagnosed within one year of recruitment. For instance, the HR for colorectal cancer per standard deviation increment in SII was estimated at 1.09 (95% CI 1.02–1.16) in blood drawn five years prior to diagnosis and 1.50 (95% CI 1.24–1.80) in blood drawn one month prior to diagnosis. We observed associations between systemic inflammation markers and risk for several cancers. The increase in risk the last year prior to diagnosis may reflect a systemic immune response to an already present, yet clinically undetected cancer. Blood cell ratios could serve as biomarkers of cancer incidence risk with potential for early identification of disease in the last year prior to clinical diagnosis.

Abstract P061: Dairy Consumption, Dairy Fat Biomarkers And Type 2 Diabetes Risk After Myocardial Infarction

Introduction: Dairy consumption, especially yogurt, and circulating biomarkers of dairy fat (odd chain fatty acids, OCFAs), have been associated with a lower risk of type 2 diabetes (T2D) in population-based studies. Whether these associations are also present in post-myocardial infarction (MI) patients is unknown. Hypothesis: We hypothesized that dairy consumption and circulating OCFAs (pentadecanoic [15:0] plus heptadecanoic acid [17:0]) may be inversely associated with incident T2D after MI. Methods: We included 3347 Dutch post-MI patients from the Alpha Omega Cohort, who were initially free of T2D. At baseline (2002-2006), dairy consumption was estimated with a 203-item food frequency questionnaire and plasma OCFAs were measured in cholesteryl esters using gas chromatography. Incident T2D was ascertained through self-reported physician diagnosis and medication use. Multivariable Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CI) for incident T2D and dairy types and OCFAs (per 1 standard deviation (SD) increment). Results: At baseline, patients were on average 68.9 years old (± 5.5 SD), 80% were men and 87% used statins (2684 and 2908 of 3347 patients respectively). During a median follow-up time of 40 months (10,550 person-years), 181 patients developed T2D. Almost all patients consumed dairy (3300 of 3347), with a median intake of 273 g/d for total dairy. After multivariable adjustment, dairy and its subtypes consumption was not associated with T2D incidence, with HRs ranging from 1.01 to 1.07 per 1-SD increment (all p> 0.05). When analysed in categories (highest vs lowest intake), HRs (95% CI) were 1.05 (0.73-1.52) for milk and 1.08 (0.77-1.51) for yoghurt intake. In line with these findings, no significant association was found for circulating OCFAs 0.97 (0.83-1.12)( Figure 1 ). Conclusion: Dairy consumption, based on self-report and plasma biomarkers, was neutrally associated with T2D incidence in a population of Dutch post-MI patients with a relatively high habitual dairy intake.

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

Background: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited.Results: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV.Conclusions: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV.Materials and methods: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.

A urinary peptidomic profile predicts outcome in SARS-CoV-2-infected patients.

BackgroundCOVID-19 prediction models based on clinical characteristics, routine biochemistry and imaging, have been developed, but little is known on proteomic markers reflecting the molecular pathophysiology of disease progression.MethodsThe multicentre (six European study sites) Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection Study (Crit-COV-U) is recruiting consecutive patients (≥ 18 years) with PCR-confirmed SARS-CoV-2 infection. A urinary proteomic biomarker (COV50) developed by capillary-electrophoresis-mass spectrometry (CE-MS) technology, comprising 50 sequenced peptides and identifying the parental proteins, was evaluated in 228 patients (derivation cohort) with replication in 99 patients (validation cohort). Death and progression along the World Health Organization (WHO) Clinical Progression Scale were assessed up to 21 days after the initial PCR test. Statistical methods included logistic regression, receiver operating curve (ROC) analysis and comparison of the area under the curve (AUC).FindingsIn the derivation cohort, 23 patients died, and 48 developed worse WHO scores. The odds ratios (OR) for death per 1 standard deviation (SD) increment in COV50 were 3·52 (95% CI, 2·02–6·13, p <0·0001) unadjusted and 2·73 (1·25–5·95, p = 0·012) adjusted for sex, age, baseline WHO score, body mass index (BMI) and comorbidities. For WHO scale progression, the corresponding OR were 2·63 (1·80–3·85, p<0·0001) and 3·38 (1·85–6·17, p<0·0001), respectively. The area under the curve (AUC) for COV50 as a continuously distributed variable was 0·80 (0·72–0·88) for mortality and 0·74 (0·66–0·81) for worsening WHO score. The optimised COV50 thresholds for mortality and worsening WHO score were 0·47 and 0·04 with sensitivity/specificity of 87·0 (74·6%) and 77·1 (63·9%), respectively. On top of covariates, COV50 improved the AUC, albeit borderline for death, from 0·78 to 0·82 (p = 0·11) and 0·84 (p = 0·052) for mortality and from 0·68 to 0·78 (p = 0·0097) and 0·75 (p = 0·021) for worsening WHO score. The validation cohort findings were confirmatory.InterpretationThis first CRIT-COV-U report proves the concept that urinary proteomic profiling generates biomarkers indicating adverse COVID-19 outcomes, even at an early disease stage, including WHO stages 1–3. These findings need to be consolidated in an upcoming final dataset.FundingThe German Federal Ministry of Health funded the study.

Relationship of Soluble Interleukin-6 Receptors With Asthma: A Mendelian Randomization Study.

Purpose: Emerging evidence suggests a potential role of interleukin-6 pathways—trans-signaling with soluble interleukin-6 receptors—in the asthma pathobiology. Despite the evidence for their associations with asthma, the causal role of soluble interleukin-6 receptors remains uncertain. We investigated the relations of soluble interleukin-6 receptors with asthma and its major phenotypes.Methods: We conducted a two-sample Mendelian randomization study. As genetic instruments, we selected 33 independent cis-acting variants strongly associated with the level of plasma soluble interleukin-6 receptor in the INTERVAL study. To investigate the association of variants with asthma and its phenotypes, we used genome-wide association study data from the UK Biobank. We combined variant-specific causal estimates by the inverse-variance weighted method for each outcome.Results: Genetically-instrumented soluble interleukin-6 receptor level was associated with a significantly higher risk of overall asthma (OR per one standard deviation increment in inverse-rank normalized soluble interleukin-6 receptor level, 1.02; 95%CI, 1.01–1.03; P = 0.004). Sensitivity analyses demonstrated consistent results and indicated no directional pleiotropy—e.g., MR-Egger (OR, 1.03; 95%CI, 1.01–1.05; P = 0.002; Pintercept =0.37). In the stratified analysis, the significant association persisted across asthma phenotypes—e.g., childhood asthma (OR, 1.05; 95%CI, 1.02–1.08; P < 0.001) and obese asthma (OR, 1.02; 95%CI 1.01–1.03; P = 0.007). Sensitivity analysis using 16 variants selected with different thresholds also demonstrated significant associations with overall asthma and its phenotypes.Conclusion: Genetically-instrumented soluble interleukin-6 receptor level was causally associated with modestly but significantly higher risks of asthma and its phenotypes. Our observations support further investigations into identifying specific endotypes in which interleukin-6 pathways may play major roles.

Association of Pulmonary Function With Cognitive Decline in Older Adults: A Nationwide Longitudinal Study in China.

This study aimed to examine whether pulmonary function and cognition are independently associated at multiple time points. We included 8264 participants (49.9% women) aged 50-94 years at baseline from the China Health and Retirement Longitudinal Study in our analysis. Participants were enrolled in 2011 and followed up in 2013 and 2015. Cognitive function was assessed through a face-to-face interview in each survey. Pulmonary function was assessed via peak expiratory flow. Pulmonary function and cognitive function decreased significantly with age in both genders. Individuals in quintile 5 of pulmonary function had a relative increase in immediate memory (β [95% CI]: 0.19 [0.09, 0.30]) and delayed memory (0.16 [0.04, 0.28]) during follow-up compared with those in quintile 1. In the repeated-measures analysis, each standard deviation increment of pulmonary function was associated with a 0.44 (95% CI: 0.34, 0.53), 0.12 (0.09, 0.15), 0.12 (0.08, 0.16), 0.08 (0.06, 0.11), and 0.10 (0.07, 0.14) higher increase in global cognitive score, immediate memory, delayed memory, orientation, and subtraction calculation, respectively. The inverse association between pulmonary function and cognitive decline during follow-up was more evident in women (p for interaction = .0333), low-educated individuals (p for interaction = .0002), or never smokers (p for interaction = .0412). In conclusion, higher baseline pulmonary function was independently associated with a lower rate of cognitive decline in older adults. The positive association between pulmonary function and cognition was stronger in women, lower-educated individuals, or never smokers.

Physical Activity and the Risk of COVID-19 Infection and Mortality: A Nationwide Population-Based Case-Control Study.

Regular physical activity (PA) is known to reduce the risk of serious community-acquired infections. We examined the association of PA with the morbidity and mortality resulting from coronavirus disease (COVID-19) infection in the South Korean population. Patients who tested positive for severe acute respiratory coronavirus 2 and who underwent public health screening between 2014 and 2017 (n = 6288) were included. Age- and sex-matched controls (n = 125,772) were randomly selected from the Korean National Health Insurance Service database. Leisure-time PA was assessed using a self-reported questionnaire. The mean PA levels were lower in the patient than in the control group (558.2 ± 516.3 vs. 580.2 ± 525.7 metabolic equivalent of task (MET)-min/week, p = 0.001). Patients with moderate to vigorous PA (MVPA) were associated with a lower risk of COVID-19 morbidity (odds ratio (OR), 0.90; 95% confidence interval (CI), 0.86–0.95). In addition, a standard deviation (SD) increment in MET/week (525.3 MET-min/week) was associated with a 4% decrease in the risk of COVID-19 morbidity (OR, 0.96; 95% CI, 0.93–0.99). MVPA and an SD increment in MET/week were associated with lower mortality (MVPA: OR, 0.47; 95% CI, 0.26–0.87; per SD increment: OR, 0.65; 95% CI, 0.48–0.88). Higher levels of regular PA were associated with a lower risk of COVID-19 infection and mortality, highlighting the importance of maintaining appropriate levels of PA along with social distancing amid the COVID-19 pandemic.

White Blood Cells and Severe COVID-19: A Mendelian Randomization Study.

Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.

Psychological factors as the risk factor of mouth ulcers: A two-sample Mendelian randomization study.

To examine whether psychological traits (PT) had causal effects on Mouth Ulcers (MU), we applied two-sample Mendelian randomization (MR) to genetics association summary statistics of eleven PT and MU. After the adjustment of outlier variants, genetic correlations and multiple testing, well-being (WB) spectrum PT like life satisfactory (odds ratio [OR] = 0.638 per one standard deviation increment of PT score) had protective effects on MU. Reverse WB traits like neuroticism (OR = 1.60) increased the risk of MU. The lack of well-being characteristics may increase the risk of MU, which highlighted the value of preventive oral care for people who have a reverse mental condition.

ESRα Promoter Methylation May Modify the Association Between Lipid Metabolism and Type 2 Diabetes in Chinese Farmers.

Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM).Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured.Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05).Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.

Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity and disability globally. This study aims to investigate the causal effects of varying blood levels of five minerals -- iron, zinc, copper, calcium, and magnesium, on OA and RA. We performed two-sample Mendelian randomization (MR) analyses to assess the associations of five circulating minerals with OA and RA. Single nucleotide polymorphisms (SNPs) serving as genetic instruments for the circulating mineral levels were selected from large genome-wide association studies of European-descent individuals. The associations of these SNPs with OA and RA were evaluated in UK Biobank participants. Multiple sensitivity analyses were applied to detect and correct for the presence of pleiotropy. Genetically determined copper and zinc status were associated with OA, but not with RA. Per standard deviation (SD) increment in copper increases the risk of OA (OR=1.07, 95% CI: 1.02-1.13) and one of its subtypes, localized OA (OR=1.08, 95% CI: 1.03-1.15). Per SD increment in zinc is positively associated with risks of OA (OR=1.07, 95% CI: 1.01-1.13), generalized OA (OR=1.18, 95% CI: 1.05-1.31), and unspecified OA (OR=1.21, 95% CI: 1.11-1.31). Additionally, per SD increment in calcium decreases the risk of localized OA (OR=0.83, 95% CI: 0.69-0.98). Genetically high zinc and copper status were positively associated with OA, but not with RA. Given the modifiable nature of circulating mineral status, these findings warrant further investigation for OA prevention strategies.

Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study.

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01–1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01–1.48 and 1.27, 1.01–1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.

Fat mass to fat-free mass ratio and the risk of non-alcoholic fatty liver disease and fibrosis in non-obese and obese individuals

ContextBody composition may explain partially why non-obese individuals still at the risk of developing non-alcoholic fatty liver disease (NAFLD). The ratio of fat mass to fat-free mass (FM/FFM) has been proposed to assess the combined effect of different body compositions.ObjectiveWe aimed to investigate the associations of FM/FFM ratio with the risk of developing NAFLD and fibrosis and to identify the potential mediators according to obesity status.MethodsThis cohort study comprised 3419 adults age ≥ 40 years and free of NAFLD at baseline. Body composition was measured by bioelectrical impedance analysis. NAFLD was ascertained by ultrasonography and fibrosis was assessed by non-invasive score systems.ResultsFor each 1 standard deviation increment in FM/FFM ratio, the odds ratio for the risk of NAFLD was 1.55 (95% confidence interval [CI] 1.23–1.95) in non-obese men, 1.33 (95% CI 1.08–1.65) in obese men, 1.42 (95% CI 1.44–1.67) in non-obese women, and 1.29 (95% CI 1.12–1.50) in obese women. Similar associations were also found between FM/FFM ratio and NAFLD with fibrosis. Mediation analysis showed that insulin resistance, triglycerides, high-density lipoprotein cholesterol, white blood cells, and total cholesterol mediated the association of FM/FFM ratio with NAFLD risk in specific sex and obesity subgroups.ConclusionsThe FM/FFM ratio significantly associated with the NAFLD and fibrosis risk in both non-obese and obese individuals. Different factors may mediate the association between body composition and NAFLD risk according to different obesity status.

Association between plasma copper levels and first stroke: a community-based nested case–control study

ABSTRACT Background and aims Uncertainty remains regarding the association between the risk of stroke and plasma copper levels in population with copper mostly in normal range due to limited data. We examined the association between baseline plasma copper and risk of first stroke in Chinese community-dwelling population. Methods We conducted a nested case control study from ‘H-type Hypertension and Stroke Prevention and Control Project’. A total of 1255 first stroke cases and 1255 controls matched for age, sex and study site were included in the analysis. Conditional logistic regression analyses were performed to evaluate the association between plasma copper and first stroke. Results The overall mean of copper was 15.90 (2.66) μmol/L. In total, 94.26% participants’ copper concentration was in the normal range by Mayo Clinic laboratory reference values. Smoothing curve showed that the associations of plasma copper with first stroke and its subtypes were linear. Each standard deviation (SD) increment of plasma copper was independently and positively associated with risk of first stroke [odds ratio (OR): 1.17, 95% confidence interval (CI): 1.07–1.28]. The multivariable ORs with 95% CIs for total stroke, ischemic stroke and hemorrhagic stroke in the highest versus the lowest quartile of plasma copper were 1.49 (1.16–1.90; P-trend = 0.001), 1.46 (1.12–1.92; P-trend = 0.004) and 2.05 (0.95–4.38; P-trend = 0.050), respectively. Conclusions Baseline plasma copper was positively associated with risk of first ischemic stroke in an approximately linear fashion among Chinese community population (80.32% hypertensives), although their copper levels were mostly within the normal range according to current reference values. Our findings warrant additional investigation.

Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA)

BackgroundHypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP).MethodsWe assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level.ResultsThe mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16−) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure.ConclusionThese findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

Anthropometric risk factors for ovarian cancer in the NIH-AARP Diet and Health Study

ObjectiveIdentifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer.MethodsWe ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50–72 years (median follow-up 12.6 years), from the National Institutes of Health—American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist–hip ratio, waist–height ratio, body adiposity index, body shape index, and abdominal volume index.ResultsAnthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88–1.10). Similar associations were observed with measurements of body fat distribution.ConclusionThese results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women.

Iodine Modifies the Susceptibility of Thyroid to Fluoride Exposure in School-age Children: a Cross-sectional Study in Yellow River Basin, Henan, China.

Excessive fluoride exposure has detrimental effects on the thyroid gland, which may be modified by iodine. However, the role of iodine in it remains unclear. This study aims to evaluate the role of iodine in thyroid abnormalities caused by fluoride exposure in school-age children. A total of 446 children aged 7-12 years were recruited from Tongxu County, Henan province, in 2017 (ZZUIRB 2017-018). We obtained demographic information through questionnaire surveys. The concentrations of urinary fluoride (UF) and urinary iodine (UI) were determined by the ion-selective electrode method and the catalytic spectrophotometric method, respectively. The radiation immunoassay was used to determine the serum concentrations of total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH). The B-mode ultrasound was performed to assess thyroid volumes (Tvols). The associations between fluoride exposure and thyroid-related indicators were tested by linear regression models. We found that Tvols increased by 0.22 (95% CI: 0.14, 0.31) cm3 with each standard deviation increment of UF. Moreover, Tvols in boys were more susceptible to fluoride exposure than those in girls, and the Tvols of children with high urinary iodine are less susceptible to fluoride exposure (P for interaction < 0.05). We also observed that TT3 levels were negatively related to UF concentrations at moderate urinary iodine levels (≤ 300 μg/l). Fluoride exposure can elevate the Tvols of school-age children, especially in boys, and high levels of iodine may alleviate this effect to some extent.

Body mass index and waist circumference in relation to the risk of 26 types of cancer: a prospective cohort study of 3.5 million adults in Spain

BackgroundA high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC.MethodsProspective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites.ResultsAfter a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m2 increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers.ConclusionsIn this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity.

Association between Albumin, Total Bilirubin, and Uric Acid Serum Levels and the Risk of Cancer: A Prospective Study in a Korean Population.

PurposeIn this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population.Materials and MethodsA total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed.ResultsUA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01–1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88–0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80–0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83–0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer.ConclusionThe findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.

Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women.

Objective:This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort.Methods:A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996–2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk.Results:We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90–1.17) for total fat, 1.06 (0.93–1.20) for saturated fat, 1.06 (0.93–1.21) for monounsaturated fat, and 1.00 (0.89–1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status.Conclusions:In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.