Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants.

BACKGROUND: Plasma proteins are potential biomarkers for complex diseases. We aimed to identify plasma protein biomarkers for lung cancer. METHODS: We investigated genetically predicted plasma levels of 1130 proteins in association with lung cancer risk among 29,266 cases and 56,450 controls of European descent. For proteins significantly associated with lung cancer risk, we evaluated associations of genetically predicted expression of their coding genes with the risk of lung cancer. RESULTS: Nine proteins were identified with genetically predicted plasma levels significantly associated with overall lung cancer risk at a false discovery rate (FDR) of <0.05. Proteins C2, MICA, AIF1, and CTSH were associated with increased lung cancer risk, while proteins SFTPB, HLA-DQA2, MICB, NRP1, and GMFG were associated with decreased lung cancer risk. Stratified analyses by histological types revealed the cross-subtype consistency of these nine associations and identified an additional protein, ICAM5, significantly associated with lung adenocarcinoma risk (FDR < 0.05). Coding genes of NRP1 and ICAM5 proteins are located at two loci that have never been reported by previous GWAS. Genetically predicted blood levels of genes C2, AIF1, and CTSH were associated with lung cancer risk, in directions consistent with those shown in protein-level analyses. CONCLUSION: Identification of novel plasma protein biomarkers provided new insights into the biology of lung cancer.

Serum Lipid Profiles and Cholesterol-Lowering Medication Use in Relation to Subsequent Risk of Colorectal Cancer in the UK Biobank Cohort.

BACKGROUND: Dyslipidemia is closely associated with metabolic syndrome, a known risk factor for colorectal cancer. However, the association of dyslipidemia with colorectal cancer risk is controversial. Most previous studies did not consider cholesterol-lowering medication use at the time of lipid measurements, which could bias findings. METHODS: We analyzed data from 384,862 UK Biobank participants to disentangle the associations between blood lipids and colorectal cancer risk. Serum levels of total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglyceride were measured at study baseline. Multivariable-adjusted Cox models were used to estimate HRs and 95% confidence intervals (CI). RESULTS: During a median follow-up time of 8.2 years, 3,150 incident primary colorectal cancer cases were identified. Triglyceride levels were positively, while HDL-C levels were inversely associated with colorectal cancer risk (both Ptrend < 0.005). No significant associations were found for total cholesterol and LDL-C. However, among nonusers of cholesterol-lowering medications, a high total cholesterol level (> 6.7 mmol/L, HR = 1.11; 95% CI, 1.00-1.24) and LDL-C level (>4.1 mmol/L, HR = 1.11; 95% CI, 0.99-1.23) was associated with an increased colorectal cancer risk compared with the referent group (5.2-6.2 mmol/L and 2.6-3.4 mmol/L for total and LDL cholesterol, respectively). Compared with nonusers, cholesterol-lowering medication users had 15% increased colorectal cancer risk (HR = 1.15; 95% CI, 1.04-1.26). CONCLUSIONS: Circulating total cholesterol, LDL-C, HDL-C and triglyceride were modestly associated with colorectal cancer risk. IMPACT: Our findings call for careful consideration of cholesterol-lowering medication use in future studies of blood lipid-colorectal cancer associations.

Autoimmune conditions and pancreatic cancer risk in older American adults.

Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values <.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.

Hemochromatosis, Iron Overload-Related Diseases, and Pancreatic Cancer Risk in the Surveillance, Epidemiology, and End Results (SEER)-Medicare.

BACKGROUND: Experimental studies suggest that iron overload might increase pancreatic cancer risk. We evaluated whether prediagnostic hemochromatosis and iron-overload diseases, including sideroblastic and congenital dyserythropoietic anemias, and non-alcoholic-related chronic liver disease (NACLD) were associated with pancreatic cancer risk in older adults. METHODS: We conducted a population-based, case-control study within the U.S. Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Incident primary pancreatic cancer cases were adults > 66 years. Controls were alive at the time cases were diagnosed and matched to cases (4:1 ratio) by age, sex, and calendar year. Hemochromatosis, iron-overload anemias, and NACLD were reported 12 or more months before pancreatic cancer diagnosis or control selection using Medicare claims data. Adjusted unconditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI) between hemochromatosis, sideroblastic and congenital dyserythropoietic anemias, NACLD, and pancreatic cancer. RESULTS: Between 1992 and 2015, 80,074 pancreatic cancer cases and 320,296 controls were identified. Overall, we did not observe statistically significant associations between hemochromatosis, sideroblastic anemia, or congenital dyserythropoietic anemia and pancreatic cancer; however, sideroblastic anemia was associated with later primary pancreatic cancer (OR, 1.30; 95% CI, 1.03-1.64). NACLD was associated with first (OR, 1.10; 95% CI, 1.01-1.19), later (OR, 1.17; 95% CI, 1.02-1.35), and all (OR, 1.12; 95% CI, 1.04-1.20) pancreatic cancer. CONCLUSIONS: Overall hemochromatosis and iron-overload anemias were not associated with pancreatic cancer, whereas NACLD was associated with increased risk in this large study of older adults. IMPACT: These results partly support the hypothesis that iron-overload diseases increase pancreatic cancer risk.

Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.

BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHODS: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. RESULTS: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSIONS: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.

Dietary inflammatory index and risk of colorectal adenoma: effect measure modification by race, nonsteroidal anti-inflammatory drugs, cigarette smoking and body mass index?

PURPOSE: To investigate if the association between dietary inflammatory potential and colorectal adenoma (CRA) is modified by race and factors known to modulate inflammation. METHODS: We examined effect measure modification of race, nonsteroidal anti-inflammatory drugs (NSAIDs), cigarette smoking and body mass index (BMI) on the diet-CRA association by employing energy-adjusted dietary inflammatory index (E-DII™) to characterize dietary inflammatory potential among 587 cases and 1,313 controls participating in a colonoscopy screening-based cross-sectional study of CRA. Participants completed a food frequency questionnaire from which E-DII score was derived. E-DII score was calculated from 34 food parameters (constituents), utilizing an energy-adjusted global comparative database to compute z scores from which centered proportions were summed to create the score. CRA cases were defined as individuals whose colonoscopy detected at least one pathologically confirmed adenomatous polyp. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A pro-inflammatory diet was not statistically significantly associated with elevated CRA risk (OR 1.07; 95% CI 0.97-1.19; p value = 0.18) in the multivariate regression model. NSAIDs use (ORnever-users 1.19; 95% CI 1.03-1.38; ORever-users 0.96; 95% CI 0.83-1.12; Pinteraction = 0.04) and race (ORAfrican Americans 1.22; 95% CI 1.03-1.44; OREuropean Americans 0.99; 95% CI 0.86-1.14; Pinteraction = 0.14) appeared to modify the association, whereas cigarette smoking and BMI did not (Pinteraction = 0.40 and 0.78, respectively). CONCLUSION: NSAIDs use and race may modify the diet-CRA association. Further investigation in prospective cohort studies is warranted to confirm these findings.

Racial Disparities in Epigenetic Aging of the Right vs Left Colon.

There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.

A novel bamboo sheet chair and its influence on sitting comfort.

BACKGROUND: In today's economy, workers spend increasingly more time in seated positions, leading to a growing scientific interest in chair design. In this study we used body pressure distribution tests to compare a novel bamboo chair with unique structural features to other commonly-used chairs. We studied the bamboo sheet chair's physical characteristics and comfort to provide a scientific theoretical basis for common use seat design. METHODS: A total of 25 (14 male and 11 female) subjects participated in the study. Subjects were divided into six groups according to their body characteristics parameters included stature, weight, shoulder breadth, hip breadth, waist width, popliteal height, buttocks-popliteal length, and buttock-abdomen depth, with three groups for males and three groups for females. Each subject was required to complete specified body pressure tests for three different experimental chairs for three minutes and subjective comfort evaluations were also administered. The pressure indexes were measured from the seat pan and backrest and calculated with MATLAB 2015b, which mainly included maximum pressure (Pm), average pressure (Pa), pressure exponent (Pe) and contact area index (P AI ). Three pressure threshold limits of 0.67 kPa, 4.00 kPa and 9.33 kPa and four contact surface indexes were used in the experiment to reflect the contact area between human and chair. RESULTS: The contact areas in the backrest (52.96 ± 32.94 cm2) and seat pan (307.75 ± 90.31 cm2) in the middle-to-high threshold pressure range, and the contact areas of the backrest (4.34 ± 5.95 cm2) in the high threshold pressure range of bamboo sheet chair were smaller than the corresponding indexes of the common office chair (81.430 ± 45.04 cm2, p = 0.00; 394.39 ± 98.99 cm2, p = 0.02; 13.54 ± 12.00 cm2, p = 0.00, respectively). The pressure index (2.68 ± 0.88 kPa), maximum pressure (6.66 ± 2.05 kPa), and average pressure (2.42 ± 0.59 kPa) values of the bamboo sheet chair backrest were also found to be lower than those of the office chair (4.32 ± 1.62 kPa, p = 0.00; 10.50 ± 3.88 kPa, p = 0.00; 3.43 ± 0.97 kPa, p = 0.00, respectively). The average pressure on the seat pan was greater than 4 kPa for all subjects, while the average pressure on the seat pan was greater than 9.33 kPa for male subjects with a body mass index (BMI) of 27.48. DISCUSSION: The bamboo sheet chair's contact areas within the middle-to-high and high-pressure threshold ranges of the backrest and seat pan were smaller than those of the office chair, indicating that the bamboo sheet chair is effective at relieving pressure. Human body characteristics must be considered in the design of seat functional size. Buttocks-popliteal length, weight, body mass index, body shape and weight distribution, all have important effects on the distribution of body pressure at the human-chair interface.

Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk.

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Effect of Chemical Treatments on the Properties of High-Density Luffa Mattress Filling Materials.

Luffa is a lightweight porous material with excellent biocompatibility and abundant resources. In this paper, three kinds of softening treatment methods, alkali-hydrogen peroxide (Method 1), alkali-acetic acid (Method 2), and alkali-urea (Method 3), were used to soften high-density (HD) cylindrical luffa (CL) mattress-filling materials (MFM). Microscopic observation, mechanical performance testing and other analyses were performed to evaluate the effects of the three kinds of softening methods on the wettability, compression resilience and support performance of CL MFM. The results showed that: (1) After the treatment by Method 1, Method 2 and Method 3, the peak stress of CL decreased by 73%, 10% and 27%, respectively. In addition, after three kinds of softening treatments, the uniformity of CL increased. (2) When the CL MFM of high density rank treated by Method 1 was compressed by 40%, the firmness values of the surface, core and bottom reduced by 53.49% 40.72%, and 46.17%, respectively, compared to that of untreated CL. In addition, for the CL MFM of high density rank treated by Method 3 and then compressed to 60%, the firmness of the surface layer, core layer and bottom layer reduced by 41.2%, 33.7%, and 36.9%, respectively. (3) The contact angle of luffa treated by Method 3 was the smallest, next came Method 1 and Method 2, and untreated was the largest. (4) After the treatment by Method 3, the fiber bundle of luffa was intact, and the compression resilience of the CL was obviously increased. Therefore, this method can effectively reduce the firmness of MFM and also improve the uniformity and wettability of CL.

Properties of Two-Variety Natural Luffa Sponge Columns as Potential Mattress Filling Materials.

Luffa sponge (LS) is a resourceful material with fibro-vascular reticulated structure and extremely high porosity, which make it a potential candidate for manufacturing light mattress. In this study, two types of LS columns, namely high-density (HD) and low-density (LD) columns, were investigated as materials for filling the mattress. The results showed that the compressive strength of HD LS columns was significantly greater than that of LD LS columns. However, the densification strains of the two types of LS column were both in the range of 0.6 to 0.7. Besides, HD LS columns separately pressed to the smooth plateau region and the initial densification region exhibited a partial recovery of instant height when they were unloaded, and then both of them showed no more than 4.2% of height recovery after being allowed to rest at a constant temperature and humidity for 24 h. In contrast, when LD LS columns were compressed to the smooth plateau region, the height recovery was less than 1.62% compared to when they were pressed to the initial densification region, and that was more than 15.62%. Similar to other plant fibers used as mattress fillers, the two types of LS columns also showed good water absorption capacity-both of them could absorb water from as much as 2.07 to 3.45 times their own weight. At the same time, the two types of LS columns also showed good water desorption. The water desorption ratio of HD and LD LS columns separately reached 76.86 and 91.44%, respectively, after being let rest at a constant temperature and humidity for 13 h.

[Energy upconversion from rare earth Er doped ZnF2: PbF4].

Energy-upconversion meterials were produced by adding Er3+ and Yb3+ ions to lead fluoride, zirconium fluoride or zinc fluoride under specific conditions. Under the excitation of infrared light at 980 nm, the material samples emit relatively strong multi-band visible light, which comes into view by naked eyes. Based onthe experiment, the multi-band visible spectral lines of Er3+ were analyzed, the energy level transition mechanism was given, and the effect of rare earth doping concentration on the energy upconversion efficiency was analyzed, according to the different upconversion light emitting intensity from samples with different Er3+ mol concentrations.

[The properties of energy upconversion of Yb(3+) -doped materials based on ZrF4].

There have been few reports on studies of energy upconversion from Yb(3+) -doped materials based on oxide, fluoride or oxyfluoide, because researches commonly considered that Yb3+ was only a good sensibilizer. This paper reports the properties of energy upconversion of Yb(3+) -doped materials based on ZrF4. The rare earth Yb3+ was doped in the ZrF4 glass under the specific condition. Using 980 nm laser as an excitation light, the upconversion fluorescence spectra of the sample were measured, and the red band, green band, blue band and purple band observed, respectively. The peaks were at 412, 478, 558 and 671 nm, respectively. This paper reports the upconversion from Yb3+ standard energy level to Yb3+ energy level 2 F7/2.