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PDF file - 113K, Odds ratios with 95% Confidence Intervals (CI) of lung cancer for circulating levels of Tryptophan, Kynurenine and Kynurenine/Tryptophan ratio by smoking status. P for trend were assessed by the base 2 logarithm of the circulating levels.

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Supplementary Tables 1-3 from A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Introduction: Chronic infection with hepatitis B (HBV) and C viruses (HCV) as well as cigarette smoking are established risk factors of hepatocellular carcinoma (HCC), but it is unclear whether an interaction exists between these factors in causing hepatocellular carcinogenesis. We conducted a meta-analysis to evaluate the interaction of HBV and HCV infection and cigarette smoking on the risk of HCC.Methods: We systematically searched the PUBMED and the China National Knowledge Infrastructure databases. A total of 16 eligible publications were identified. Cigarette smoking and chronic HBV and HCV infections were dichotomized into present or absent. Additive (S) and multiplicative interaction indexes (V) between smoking and each of the two infections and their 95% confidence intervals (95% CI) were calculated for each study and then combined in a meta-analysis.Results: We found a more than additive interaction between HBV infection and cigarette smoking (S = 1.44; 95% CI, 1.00-2.06; nine studies) and a more than multiplicative interaction (V = 1.60; 95% CI, 1.16-2.20; six studies) between HCV infection and cigarette smoking. No publication bias was detected.Conclusion: Smoking seems to interact with both HBV and HCV in determining HCC risk. A pooled analysis of individual subject data, with appropriate adjustment with other risk factors, is warranted to confirm these results.Impact: The results of this study imply the evidence of a synergistic effect between smoking and HBV or HCV infection on the risk of HCC. Thus, chronic carriers of HBV or HCV are recommended to avoid smoking. Cancer Epidemiol Biomarkers Prev; 19(5); 1261–8. ©2010 AACR.

PDF file - 71K, Spearman partial correlation coefficients between biomarkers among controls of a nested case-control study in the EPIC cohort.

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PDF file - 100K, Odds Ratios with 95% Confidence Intervals (CI) of Lung Cancer for circulating levels of Tryptophan, Kynurenine and Kynurenine/Tryptophan ratio by histological type. P for trend were assessed by the base 2 logarithm of the circulating levels.

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Background: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention.Methods: We pooled data from 12 case–control studies including 6,448 cases and 13,747 controls, and estimated OR and 95% CI for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use, and body mass index.Results: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI: 0.95–1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI: 1.22–2.07), and no association among ever smokers (OR, 0.96; 95% CI: 0.83–1.11); likelihood ratio test for interaction P = 0.001.Conclusion: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes.Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC. Cancer Epidemiol Biomarkers Prev; 21(2); 294–304. ©2011 AACR.

Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer.Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk.Results: Tryptophan (Ptrend = 2 × 10−5) and the kynurenine/tryptophan ratio (KTR; Ptrend = 4 × 10−5) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th vs. 1st) were 0.52 [95% confidence interval (CI), 0.37–0.74] for tryptophan and 1.74 (95% CI, 1.24–2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR (Ptrend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62–4.94, Ptrend = 3 × 10−5) that was only marginally affected by adjusting for methionine.Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology.Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk. Cancer Epidemiol Biomarkers Prev; 23(3); 461–8. ©2013 AACR.

PDF file - 98K, Odds ratios with 95% Confidence Intervals (CI) of lung cancer for circulating levels of Kynurenic acid, 3-Hydroxykynurenine, Anthralinic acid, Xanthurenic acid, 3-Hydroxyantranilic acid and Neopterine. P for trend were assessed by the base 2 logarithm of the circulating levels.

Supplementary Tables 1-2 from Interaction between Cigarette Smoking and Hepatitis B and C Virus Infection on the Risk of Liver Cancer: A Meta-analysis

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Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies.Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sexdifference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86).Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers.Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.

Aims Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Methods Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies. Results PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. Conclusion Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514–525.

Chondrocytes in growth plates are responsible for longitudinal growth in long bones during endochondral ossification. Discoidin domain receptor 1 (Ddr1) is expressed in chondrocytes, but the molecular mechanisms by which DDR1 regulates chondrocyte behaviors during the endochondral ossification process remain undefined. To elucidate Ddr1-mediate chondrocyte functions, we generated chondrocyte-specific Ddr1 knockout (CKOΔDdr1) mice in this study. The CKOΔDdr1 mice showed delayed development of the secondary ossification center and increased growth plate length in the hind limbs. In the tibial growth plate in CKOΔDdr1 mice, chondrocyte proliferation was reduced in the proliferation zone, and remarkable downregulation of Ihh, MMP13, and Col-X expression in chondrocytes resulted in decreased terminal differentiation in the hypertrophic zone. Furthermore, apoptotic chondrocytes were reduced in the growth plates of CKOΔDdr1 mice. We concluded that chondrocytes with Ddr1 knockout exhibit decreased proliferation, terminal differentiation, and apoptosis in growth plates, which delays endochondral ossification and results in short stature. We also demonstrated that Ddr1 regulates the Ihh/Gli1/Gli2/Col-X pathway to regulate chondrocyte terminal differentiation. These results indicate that Ddr1 is required for chondrocytes to regulate endochondral ossification in skeletal development.

The forecast of typhoon tracks remains uncertain and is positively related to the accuracy of the storm surge forecast. The storm surge prediction error increases dramatically when the forecast track error is larger than 100 km. This study aims to develop an ensemble storm surge prediction system using parametric weather models to account for the uncertainty in typhoon track prediction. The storm surge model adopted in this study is COMCOT-SS storm surge forecast system. Two methods are introduced and analyzed to generate the ensemble members in this study. One is from the weather ensemble prediction system (WEPS), and the other is from the error distribution of the deterministic forecasts (EDF). The ensemble prediction results show that the ensemble mean of WEPS performs similarly to the deterministic forecast. However, the maximum surge height of WEPS is often lower than one from EDF. The verification results suggest that, for disaster prevention, EDF provides stronger warnings to the coastal region than WEPS. However, it may provide overestimated forecasts in some cases.

Highlights • More patients with chronic hepatitis B (CHB) are surviving into old age. • The late-life health-related quality of life (HRQoL) they might experience remains unclear. • We repeatedly assessed HRQoL in a cohort of older adults with CHB over five years. • The HRQoL changes older CHB patients might experience were delineated. • Extrahepatic organ/system abnormalities were associated with changes in HRQoL., Despite the increasing health burden of chronic hepatitis B (CHB) in aging populations, little is known about the course of health-related quality of life (HRQoL) changes. We aimed to assess individual-level longitudinal HRQoL changes in elderly patients with CHB and to examine their correlates. A prospective 5.1 years-cohort study was conducted in community-dwelling adults aged 55 years with hepatitis B surface antigen-positive. Participants underwent serial measurement of HRQoL using the short-form (12) health survey version 2. Of 503 participants, 82.7% remained in good physical health throughout the study period, whereas 9.1% had declining physical health and 8.2% were in poor physical health. We likewise identified three trajectories of mental health changes (“good mental health” [86.9%], “declining mental health” [6.8%], and “poor mental health” [6.4%]). Three baseline characteristics were independently associated with a lower likelihood of remaining physically or mentally healthy: sarcopenic obesity (odds ratio [OR] with 95% confidence interval [95% CI] of 7.5 [2.8–20.5] for poor physical health, 3.1 [1.1–8.4] for declining physical health, 4.3 [1.4–13.0] for poor mental health), a higher number of metabolic abnormalities (OR [95% CI] of 3.6 [1.6–8.0] for poor physical health) and depressed mood (OR [95% CI] of 21.7 [5.8–81.0] for poor physical health, 5.3 [1.4–19.9] for declining physical health, 83.1 [19.7–350.2] for poor mental health, 13.6 [2.9–64.8] for declining mental health). In conclusion, in a cohort of elderly patients with CHB, we demonstrated the heterogeneity and nonlinearity of HRQoL changes and their associations with variations in specific extrahepatic organs/systems.

Human bone marrow stem cells (HBMSCs) are isolated from the bone marrow. Stem cells can self-renew and differentiate into various types of cells. They are able to regenerate kinds of tissue that are potentially used for tissue engineering. To maintain and expand these cells under culture conditions is difficult—they are easily triggered for differentiation or death. In this study, we describe a new culture formula to culture isolated HBMSCs. This new formula was modified from NCDB 153, a medium with low calcium, supplied with 5% FBS, extra growth factor added to it, and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate to maintain the cells in a steady stage. The cells retain these characteristics as primarily isolated HBMSCs. Moreover, our new formula keeps HBMSCs with high proliferation rate and multiple linage differentiation ability, such as osteoblastogenesis, chondrogenesis, and adipogenesis. It also retains HBMSCs with stable chromosome, DNA, telomere length, and telomerase activity, even after long-term culture. Senescence can be minimized under this new formulation and carcinogenesis of stem cells can also be prevented. These modifications greatly enhance the survival rate, growth rate, and basal characteristics of isolated HBMSCs, which will be very helpful in stem cell research.

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a, EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Discoidin domain receptor 1 (Drd1) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific Ddr1 knockout (OKO&Delta, Ddr1) mice, their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1f/f-4OHT mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1f/f-4OHT mice, OKO&Delta, Ddr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKO&Delta, Ddr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKO&Delta, Ddr1 mice, H&amp, E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1f/f-4OHT. Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. Ddr1 knockdown in osteoblasts resulted in decreased mineralization, ALP activity, phosphorylated p38 and protein levels of BMP2, Runx2, ALP, Col-I and OC during osteogenesis. Overexpression and knockdown of Ddr1 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation.

We recently reported that the chondrocyte-specific knockout of discoidin domain receptors 1 (Ddr1) delayed endochondral ossification (EO) in the growth plate by reducing the chondrocyte hypertrophic terminal differentiation, and apoptosis. The biologic and phenotypic changes in chondrocytes in the articular cartilage with osteoarthritis (OA) are similar to the phenomena observed in the process of EO. Additionally, autophagy can promote chondrocyte survival and prevent articular cartilage from degradation in OA. On this basis, we explored the effect of Ddr1 inhibition on OA prevention and further investigated the roles of autophagy in treating OA with a Ddr1 inhibitor (7 rh). The anterior cruciate ligament transection (ACLT)&ndash, OA model was used to investigate the role of 7 rh in vivo. Forty 8-week-old mice were randomly assigned to four groups, including the sham group, ACLT group, and two treated groups (ACLT with 7 rh 6.9 nM or 13.8 nM). According to the study design, normal saline or 7 rh were intra-articular (IA) injected into studied knees 3 times per week for 2 weeks and then once per week for 4 weeks. The results showed that 7 rh treatment significantly improved the functional performances (the weight-bearing ability and the running endurance), decreased cartilage degradation, and also reduced the terminal differentiation markers (collagen type X, Indian hedgehog, and matrix metalloproteinase 13). Moreover, 7 rh decreased chondrocyte apoptosis by regulating chondrocyte autophagy through reducing the expression of the mammalian target of rapamycin and enhancing the light chain 3 and beclin-1 expression. These results demonstrated that the IA injection of 7 rh could reduce the chondrocyte apoptosis and promote chondrocyte autophagy, leading to the attenuation of cartilage degradation. Our observations suggested that the IA injection of 7 rh could represent a potential disease-modifying therapy to prevention OA progression.

Estrogen is an important hormone to regulate skeletal physiology via estrogen receptors. The traditional estrogen receptors are ascribed to two nuclear estrogen receptors (ERs), ER&alpha, and ER&beta, Moreover, G protein-coupled estrogen receptor-1 (GPER-1) was reported as a membrane receptor for estrogen in recent years. However, whether GPER-1 regulated osteogenic cell biology on skeletal system is still unclear. GPER-1 is expressed in growth plate abundantly before puberty but decreased abruptly since the very late stage of puberty in humans. It indicates GPER-1 might play an important role in skeletal growth regulation. GPER-1 expression has been confirmed in osteoblasts, osteocytes and chondrocytes, but its expression in mesenchymal stem cells (MSCs) has not been confirmed. In this study, we hypothesized that GPER-1 is expressed in bone MSCs (BMSC) and enhances BMSC proliferation. The cultured tibiae of neonatal rat and murine BMSCs were tested in our study. GPER-1-specific agonist (G-1) and antagonist (G-15), and GPER-1 siRNA (siGPER-1) were used to evaluate the downstream signaling pathway and cell proliferation. Our results revealed BrdU-positive cell counts were higher in cultured tibiae in the G-1 group. The G-1 also enhanced the cell viability and proliferation, whereas G-15 and siGPER-1 reduced these activities. The cAMP and phosphorylation of CREB were enhanced by G-1 but inhibited by G-15. We further demonstrated that GPER-1 mediates BMSC proliferation via the cAMP/PKA/p-CREB pathway and subsequently upregulates cell cycle regulators, cyclin D1/cyclin-dependent kinase (CDK) 6 and cyclin E1/CDK2 complex. The present study is the first to report that GPER-1 mediates BMSC proliferation. This finding indicates that GPER-1 mediated signaling positively regulates BMSC proliferation and may provide novel insights into addressing estrogen-mediated bone development.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

We examined the associations between breast cancer diagnosed during pregnancy and up to 5 years postpartum and total mortality. Breast cancer patients were identified from the Taiwan Cancer Registry (2002-2014). All pregnancies up to 5 years before breast cancer diagnosis were abstracted from the National Health Insurance database and data were then linked to the Taiwan National Death Certificate Database. Follow-up was calculated from the date of breast cancer diagnosis to the date of death or 31 December, 2014, whichever came first. The hazard ratios (HRs) and the 95% confidence intervals (CI) of the association between pregnancy and total mortality were estimated using Cox proportional hazard models. Among the 30,230 breast cancer patients, 90 were diagnosed during pregnancy, 347 within a year postpartum, and 1993 during 1-5 years postpartum. By the end of 2014, 2,920 patients were dead. The major cause of death was breast cancer (89%). Compared to patients without pregnancy records, the HRs were 1.42 (95% CI = 0.83-2.45) for patients diagnosed during pregnancy, 1.29 (0.96-1.74) for those diagnosed within a year postpartum, 1.27 (0.95-1.70) for those diagnosed within 1 to 2 years postpartum, and 1.06 (0.88-1.27) for those diagnosed ≥2 to 5 years postpartum, after adjustment for tumor characteristics and treatment. Subgroup analyses revealed an increased risk of mortality for patients diagnosed within a year postpartum in ER+ cancers (HR = 2.11, 95% CI = 1.28-3.47). Our results suggested a recent pregnancy may be associated with higher mortality among ER+ patients.

Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism.We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from5.5% to ≥7.0%).HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term.001). Compared with participants with an HbA1c of 5.5% to6.0%, those with an HbA1c of5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (48,124 pg/mL; p for interaction.05).High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend