Risk Due To Interaction Research Articles

Uric acid, renal function and risk of hypoglycaemia in Chinese type 2 diabetes patients.

This study aimed to explore independent associations between serum uric acid and hypoglycaemia, and whether mildly increased serum uric acid exacerbated the association between mild decline in estimated glomerular filtration rate (eGFR) and hypoglycaemia. A cross-sectional survey of 6713 inpatients with type 2 diabetes and eGFR ≥60mL/min/1.73m2 and admitted to 81 tertiary care hospitals in China was conducted. Self-reported asymptotic hypoglycaemia with plasma glucose ≤3.9mmol/L, hypoglycaemia episodes with symptoms in 1month or hypoglycaemia that needed assistance from other people in 3months before hospitalization was used to define hypoglycaemia. Binary logistic regression was used to estimate odds ratios of serum uric acid for hypoglycaemia. Three measures, that is, relative excess risk due to interaction (RERI), attributable proportion due to interaction and synergy index (S) were used to estimate the effect of mildly decreased eGFR on the association of serum uric acid with hypoglycaemia. Serum uric acid was associated with hypoglycaemia in an ordinal manner (P for trend <0.01) with an odds ratio of top quartile versus the lowest quartile up to 3.03 (95% confidence interval: 2.13-4.32). The odds ratio of serum uric acid levels ≥ versus <283µmol/L (i.e. the median) was 1.98 (95% confidence interval:1.58-2.48). Serum uric acid levels ≥ versus <283µmol/L greatly enhanced the association between mild decline in eGFR (eGFR < 90mL/min/1.73m2 ) and hypoglycaemia from 0.94 (0.36-2.43) to 3.90 (2.55-5.95), with a significant additive interaction (P < 0.05 for RERI, AP and S). Mildly increased serum uric acid was associated with increased risk of hypoglycaemia and enhanced the association between mildly decreased eGFR and hypoglycaemia in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491–0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537–0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120–1.238); AP: 0.427, 95% CI: 0.072–0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes.

Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia

Several food groups or dietary factors and the cervical microbiota may be involved in cervical carcinogenesis, but the evidence is not clear yet. We aimed to assess the association between dietary pattern and cervical intraepithelial neoplasia (CIN) and the combined effect of dietary pattern and cervical microbiome on the risk of CIN. The cervical microbiota and diet assessed by pyrosequencing and a food-frequency questionnaire, respectively, of 65 women with CIN and 72 control women were used in this study. Principal component analysis and cluster analysis were used to identify dietary patterns and microbiome community types, respectively. The association between dietary pattern and CIN risk was assessed using multivariable logistic regression analysis. The combined effect of dietary pattern and microbiome on CIN risk was determined using relative excess risk due to interaction (RERI) and synergy index (S). Two dietary patterns and four community types were identified: prudent diet characterized by higher intake of vegetables and fishes; semi-Western diet characterized by higher intake of bread, dairy products, eggs, and soft drinks and relatively higher fat intake ratio; and Lactobacillus crispatus-, L. iners-, Atopobium vaginae-, and Prevotella bivia-dominant types. The high-scoring group of participants with a semi-Western diet had a higher risk of CIN (odds ratio [OR] 3.44, 95% confidence interval [CI] 1.11-10.7, p=0.03), compared with the low or medium-scoring group of those with a semi-Western diet. L. iners-dominant (OR 6.39, 95% CI 1.52-26.7, p=0.01) and A. vaginae-dominant (OR 4.99, 95% CI 1.17-21.3, p=0.03) dominant types had a higher risk of CIN, compared with the L. crispatus-dominant type. The synergistic effect of semi-Western diet and A. vaginae-dominant type on CIN risk was observed (OR 20.8, 95% CI 2.21-195.6, p=0.01, RERI/S 9.64/1.96). Our findings suggest that semi-Western diet and its combination with A. vaginae-dominant microflora may represent an important risk factor for cervical neoplasia.

Joint effects of trihalomethanes and trichloroacetic acid on semen quality: A population-based cross-sectional study in China

Exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) has been individually associated with adverse male reproductive effects; however, their joint male reproductive toxicity is largely unknown. This study aimed to explore the joint effects of THMs and trichloroacetic acid (TCAA) on semen quality in a Chinese population. A total of 337 men presenting to the Reproductive Center of Tongjing Hospital, in Wuhan, China to seek semen analysis were included this study. Baseline blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA were analyzed and dichotomized at their median levels. The joint effects of THMs and TCAA on below-reference semen quality parameters were evaluated by calculating the relative excess risk due to interaction (RERI). After adjusting for potential confounders, we found a suggestive synergistic effect between Br-THMs (sum of BDCM, DBCM, and TBM) and TCAA for below-reference sperm count (RERI = 2.14, 95% CI: −0.37, 4.91) (P = 0.076); men with high Br-THMs and TCAA levels (above the median) had 3.31 times (95% CI: 1.21, 9.07) elevated risk of having below-reference sperm count than men with low Br-THMs and TCAA levels (below the median). No apparent joint effects were observed between THMs and TCAA for other semen quality parameters. Our results suggest that co-exposure to Br-THMs and TCAA is associated with additive effects on decreased semen quality. However, further studies in a larger sample size and mechanistic studies are needed to confirm the findings.

Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.

Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.

Association of Combined Tobacco Smoking and Oral Contraceptive Use With Cervical Intraepithelial Neoplasia 2 or 3 in Korean Women.

BackgroundCigarette smoking and oral contraceptive (OC) use have been associated with cervical neoplasia, and the combination of smoking and OC use could influence cervical carcinogenesis. We aimed to assess the joint effect of smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN).MethodsFrom a cohort of human papillomavirus-positive subjects recruited from 6 hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411 control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean age, 43 years). The risk of CIN associated with smoking and OC use on additive and multiplicative scales was estimated via multinomial logistic regression after adjustment for potential confounding factors. The relative excess risk due to interaction (RERI) and the synergy index (S) were used to evaluate the additive interaction.ResultsOC users (odds ratio [OR] 1.98; 95% confidence interval [CI], 1.07–3.69) and long-term OC use (≥20 months; OR 2.71; 95% CI, 1.11–6.59) had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non-OC users. Smokers and heavy smoking (≥8 cigarettes/day) were not associated with any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68–14.4; RERI/S, 3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking and long-term OC use (OR 11.5; 95% CI, 1.88–70.4; RERI/S, 9.93/18.8; P for multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no association with CIN 1 compared to combined non-smoking and non-OC use.ConclusionsOC use and smoking acted synergistically to increase the risk of CIN 2 or 3 in Korean women.

The joint effect of asbestos exposure, tobacco smoking and alcohol drinking on laryngeal cancer risk: evidence from the French population-based case–control study, ICARE

ObjectiveThe objective of the study was to investigate the joint effect of occupational exposure to asbestos, and tobacco and alcohol consumption, on the risk of laryngeal cancer among men.MethodsWe used...

Prognostic and Predictive Values and Statistical Interactions in the Era of Targeted Treatment.

The current era of targeted treatment has accelerated the interest in studying gene-treatment, gene-gene, and gene-environment interactions using statistical models in the health sciences. Interactions are incorporated into models as product terms of risk factors. The statistical significance of interactions is traditionally examined using a likelihood ratio test (LRT). Epidemiological and clinical studies also evaluate interactions in order to understand the prognostic and predictive values of genetic factors. However, it is not clear how different types and magnitudes of interaction effects are related to prognostic and predictive values. The contribution of interaction to prognostic values can be examined via improvements in the area under the receiver operating characteristic curve due to the inclusion of interaction terms in the model (ΔAUC). We develop a resampling based approach to test the significance of this improvement and show that it is equivalent to LRT. Predictive values provide insights into whether carriers of genetic factors benefit from specific treatment or preventive interventions relative to noncarriers, under some definition of treatment benefit. However, there is no unique definition of the term treatment benefit. We show that ΔAUC and relative excess risk due to interaction (RERI) measure predictive values under two specific definitions of treatment benefit. We investigate the properties of LRT, ΔAUC, and RERI using simulations. We illustrate these approaches using published melanoma data to understand the benefits of possible intervention on sun exposure in relation to the MC1R gene. The goal is to evaluate possible interventions on sun exposure in relation to MC1R.

Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2 Million Individuals.

Recent studies question whether the risk for psychotic disorder associated with prenatal exposure to infection are due to infections per se, or to shared susceptibility of both infections and psychiatric disorders. Moreover, the potential link between prenatal infection and serious infections during childhood, another alleged risk factor for psychotic disorder, remains unknown. The aim of this study was to investigate the role of maternal infections during pregnancy in context of parental psychiatric disorders and subsequent childhood infections. All children born in Sweden 1978-1997 were linked to the National Patient Register. Hazard ratios of nonaffective psychosis were estimated in relation to maternal infection during pregnancy and odds ratios of childhood infection were calculated in relation to maternal infection during pregnancy. Relative excess risk due to interaction (RERI) estimated biological synergism between parental psychiatric disorder and maternal infection during pregnancy, and between maternal infection during pregnancy and childhood infection. Maternal infection during pregnancy was not statistically significantly associated with offspring psychosis (adjusted hazard ratio: 1.06, 95% CI 0.88-1.27). However, maternal infection during pregnancy and maternal psychiatric disorders acted synergistically in offspring psychosis development (RERI 1.33, 95% CI 0.27-2.38). Maternal infection during pregnancy increased the risk of offspring childhood infections (OR 1.50, 95% CI 1.45-1.54). These 2 factors also interacted in psychosis development (RERI 0.63, 95% CI 0.12-1.14). Among mothers with a history of psychiatric disease, infection during pregnancy increases the risk of psychosis in offspring. Maternal infections during pregnancy appear to contribute to the risk of childhood infections, which together render the child more vulnerable to psychosis development.

Interactions Between Cigarette Smoking And Ambient PM2.5 For Cardiovascular Mortality In The Cancer Prevention Study-II

Introduction: Associations between long-term exposure to ambient fine particulate matter air pollution (PM2.5) and cardiovascular mortality are clearly established in the literature. However, further work is needed to investigate possible joint effects of PM2.5 and cigarette smoking for the disease. We recently reported a greater-than-additive relationship between PM2.5 and cigarette smoking for lung cancer mortality in the American Cancer Society Cancer Prevention Study-II (CPS-II) and extend this work to mortality from circulatory diseases here. Methods: Included in this analysis were 429,406 current or never cigarette smokers among whom 32,354 died of circulatory disease during 22 years of follow-up (1982-2004). We estimated PM2.5 concentrations from a national hybrid land use-kriging interpolation model for the years 1999-2004. We fit Cox proportional hazards regression models to estimate mortality associations and interactions on both the additive and multiplicative scales. Results: The hazard ratio (HR) (95% confidence interval (CI)) for high vs. low PM2.5 exposure (according to the 75th and 25th percentile) was 1.10 (95% CI 1.07-1.13) in never smokers. The HR for cigarette smoking was 1.89 (95% CI 1.82-1.96) in those with low PM2.5. The HR for both high PM2.5 and cigarette smoking was 2.10 (95% CI 2.02-2.17). There was a significant relative excess risk due to interaction (RERI) of 0.11 (95% CI 0.03-0.19) observed. There was a stronger RERI for mortality from dysrhythmias, heart failure, cardiac arrest more specifically (RERI = 0.20, 95% CI 0.01-0.40). Results using an additive hazards model will also be presented. Conclusions: There was some evidence for a small additive interaction between PM2.5 and cigarette smoking for circulatory mortality.

Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00×10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00×10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00×10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene-gene interactions involved in genetics of complex disease traits.

Association and interaction analysis of excess weight and chronic kidney disease for cardiovascular autonomic neuropathy in the general Chinese population

Background: The purpose of this study was to evaluate the associations of excess weight (EW) and/or chronic kidney disease (CKD) with cardiovascular autonomic neuropathy (CAN), and to detect the extent to which interaction of EW and CKD has on the outcome in a Chinese sample. Method: We conducted a large-scale, population-based study to analyze the association and interaction of the two factors on CAN in a sample of 2092 Chinese people. Multiple linear regression analysis to include the two main factors and its interaction were employed to detect these relationships. Relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP) and the synergy index (S) were used to estimate the effect of interaction on an additive scale can. Result: Multivariable logistic regression (MLR) indicated that body mass index (BMI) was independently associated with CAN (p = 0.006). In addition, a significant positive interaction between BMI and CKD on CAN was estimated (p = 0.042, RETI = 0.473, 95% CI: 0.0615–0.884, AP = 0.203, 95% CI: −0.055 to 0.461 and S = 1.550, 95% CI: 0.667–2.589). Conclusion: Our findings suggest that BMI is independently associated with CAN and offer evidence to support the hypothesis that excess weight and CKD have significant positive interactions on CAN.

The impact of interaction between alcohol consumption and obesity on incident hypertension

To investigate the combined effects of alcohol consumption and obesity hypertension risk. Based on data from program "Prevention of multiple metabolic disorders and metabolic syndrome in Jiangsu province", Baseline data were obtained in April 1999 to Jun 2004, we conducted the follow up investigation from March 2006 to October 2007 for subjects, those follow up time meet 5 years. A total of 4 083 participants completed the follow-up survey, and 2 778 eligible participants for final analysis. In the baseline and follow up survey, participants returned a completed questionnaire with information on diet, education, occupation, lifestyle factors, and medical history. Data on demographic characteristics, physical examination and laboratory tests were also obtained. Cox proportional hazards regression model was used to investigate the association between body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR). Logistic regression model was used to examine the interaction of alcohol consumption with WC, BMI and WHtR on risk of hypertension and the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI) were calculated. If the 95% CI of SI do not include 1, the 95% CI of RERI and AP do not include 0, the interactions are statistically significant. In the study subjects, 660 patients (254 males and 406 females) were new cases, who developed hypertension by the follow-up investigation. The mean of WC, BMI and WHtR were (23.3 ± 3.2) kg/m(2), (77.7 ± 9.0) cm and 0.49 ± 0.06, were higher than that in normal subjects ((22.4 ± 3.0) kg/m², (74.8 ± 8.5) cm and 0.47 ± 0.05, all P values < 0.001). After adjustment for age, sex, smoking status, family history of hypertension, the hazard ratio of EH for participants with obesity, high WC, high WHtR and alcohol consumption were higher, the HR (95% CI) were 2.12 (1.46-3.10), 1.64 (1.32-2.03), 2.80 (1.73-4.59) and 1.65 (1.29-2.12). HR (95% CI) of subjects with both abnormal BMI and current alcohol consumption was 2.76 (2.45-3.17), SI (95% CI) was 1.60 (0.48-5.28), RERI(95%CI) was 0.66 (-0.47-1.79) and AP was 0.24 (-0.22-0.69), HR (95% CI) of subjects with both high WC and current alcohol consumption was 4.93 (2.87-8.49), SI(95% CI) was 4.49(1.97-10.22), RERI (95%CI) was 3.06 (0.48-5.64) and AP(95% CI) was 0.62 (0.41-0.83), HR (95% CI) of subjects with both high WHtR and current alcohol consumption was 2.80 (1.73-4.59), SI (95% CI) was 2.14 (0.88-5.17), RERI was 0.96 (0.48-5.64) and AP (95% CI) was 0.34 (0.03-0.68). Both obesity, high WC, high WHtR, and alcohol consumption were strong risk factors of EH, and impact of an additive interaction of alcohol consumption and high WC on EH risk existed.

Effect of tea on oral cancer in nonsmokers and nondrinkers: a case-control study

OBJECTIVE To investigate the effect of tea on oral cancer in nonsmokers and nondrinkers. A case-control study were performed between September 2010 and January 2015 including 203 oral cancer cases in nonsmokers and nondrinkers with pathologically confirmed and 572 community controls. The related information included socio-demographic characteristics, detailed information on tobacco smoking and alcohol and tea consumption, personal medical history, family history of cancer, and occupational history were collected from all subjects. Unconditional logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI) to examine the effect of tea on oral cancer and to assess multiplicative interactions between tea and passive smoking. We also stratified by age, sex, residence, and passive smoking to explore possible difference in association between subgroups. Additive interactions between tea and passive smoking were assessed using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Compared with non-tea drinkers, tea consumption (OR = 0.52, 95% CI: 0.34-0.81), age of tea drinking initiation (years) ≥ 18 (OR = 0.54, 95% CI: 0.34-0.85), duration of tea consumption (years) < 20 (OR = 0.49, 95% CI: 0.27-0.90), duration of tea consumption (years) ≥ 20 (OR = 0.55, 95% CI: 0.32-0.95), average daily tea consumed < 700 ml (OR = 0.52, 95% CI: 0.32-0.86), moderate concentration of tea consumed (OR = 0.56, 95% CI: 0.32-0.96), weak concentration of tea consumed (OR = 0.35, 95% CI: 0.16-0.77), drinking green-tea (OR = 0.48, 95% CI: 0.28-0.82) and drinking moderate temperature of tea (OR = 0.55, 95% CI: 0.31-0.98) could reduce the risk of oral cancer; Stratified analysis indicated the protective effects of tea drinking on female (OR = 0.53, 95% CI: 0.30-0.94), age < 60 years old (OR = 0.53, 95% CI: 0.29-0.97), live in the urban (OR = 0.38, 95% CI: 0.20-0.69) and no passive smoking (OR = 0.47, 95% CI: 0.25-0.86) population with nonsmoking and nondrinking was more obvious; Crossover analysis showed tea and passive smoking did not exist multiplication interaction relationship (OR = 0.95, 95% CI: 0.41-2.20) and addition interaction relationship (RERI = -0.15, 95% CI: -0.92-0.62;AP = -0.16, 95% CI: -1.06-0.73; SI = -0.18, 95% CI: -1.44-0.87). Tea consumption, age of tea drinking initiation, duration of tea consumption, average daily tea consumed, concentration of tea consumed, types of tea and temperature of tea might have impact on the incidence of oral cancer in nonsmokers and nondrinkers to a certain extent.

Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium.

Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported. Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Obesity (BMI ≥ 30 kg/m(2)) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.

Interaction of poor sleep quality, family history of type 2 diabetes, and abdominal obesity on impaired fasting glucose: a population-based cross-sectional survey in China

This study aims to explore the interaction of sleep quality, family history of type 2 diabetes, and obesity in relation to impaired fasting glucose in a Chinese population. A representative population-based cross-sectional study was conducted, and 15,145 residents aged between 18 and 75 years were selected from 11 districts of Xuzhou City, Jiangsu Province. The Pittsburgh Sleep Quality Index was used to evaluate sleep conditions, with categories of good and poor. Impaired fasting glucose (IFG) was assessed by fasting blood glucose. Interaction of sleep quality, obesity, and family history of diabetes (FHD) on IFG was analyzed by logistic regression. Relative excess risk due to interaction (RERI) and the synergy index (SI) were applied to evaluate the additive interaction between the two factors. Either poor sleep or positive FHD was independently associated with an increased odds ratio (OR) for IFG. Those with both poor sleep and positive FHD had a significantly increased risk compared with those without poor sleep and FHD (OR 20.6, 95 % confidence interval (CI) 16.4–29.0, P < 0.001). The corresponding RERI and SI was 14.6 (8.6–20.6) and 3.7 (1.4–5.1), respectively. Both abdominal obesity and FHD significantly increased the risk of being IFG. The synergistic effect of abdominal obesity and FHD on IFG was statistically significant (OR 40.1, 95 % CI 28.8–61.5). The results suggest that additive interactions exist between poor sleep quality, abdominal obesity, and family history of diabetes in relation to impaired fasting glucose.

Synergistic effect of pain and deficits in ADL towards general practitioner visits.

Pain and activities of daily living (ADLs) deficits are common problems among elderly people who visit general practitioners (GPs). To examine whether the probability of visiting a GP is related to deficits in ADLs and pain, and whether these factors act synergistically towards GP visits. A total of 3097 subjects aged ≥65 years from the Austrian Health Interview Survey formed the cohort. Visiting the GP in the last 4 weeks, chronic pain (CP; pain for at least 3 months) and deficits in ADLs across 11 dimensions were reported. Binary logistic regression models were applied and were stepwise controlled for possible confounders. Based on odds ratios (OR), the synergy index (SI), population attributable fraction (PAF) and relative excess risk due to interaction (RERI) were calculated. Overall, 61.0% visited their GP; 51.2% were affected by ADL deficits and 42.2% by CP. In subjects with ADL deficits, the OR for GP consultation was 1.32 (95% confidence interval [CI] 1.11-1.56) and in subjects with CP, 1.93 (95% CI 1.63-2.27) in the fully adjusted model. The OR for those affected by both was 2.56 (95% CI 2.08-3.15); SI was 1.82 (95% CI 1.04-3.18), PAF was 0.27 (95% CI 0.08-0.47) and RERI was 0.70 (95% CI 0.13-1.27). There is a strong synergistic effect of CP and deficits in ADL in patients ≥65 years on visiting the GP. Prevention, screening, treatment and rehabilitation in this population should focus on both CP and ADL deficits.

The association and interaction analysis of hypertension and uric acid on cardiovascular autonomic neuropathy

The purpose of this study was to evaluate associations among hypertension (HTN) and uric acid (UA) with cardiovascular autonomic neuropathy (CAN), and to estimate the extent to which synergistic effects of HTN and UA affect the outcome in a Chinese population. We conducted a large-scale, population-based study to analyze the association and interaction of the two factors for CAN in a sample of 2092 Chinese people. Univariate and multiple linear regression (MLR) analysis were employed to detect these relationships. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). After adjusting for confounding factors, MLR showed that HTN was independently associated with CAN (P<0.001). A significant interaction effect of UA and HTN on CAN was detected (P=0.035; RETI=1.483, 95% CI 0.415-2.551; AP=0.360, 95% CI -0.043 to 0.76 and S=1.908, 95% CI 0.152-3.66). Our findings suggest that HTN is independently and significantly associated with CAN and offer evidence to support the hypothesis that HTN and UA have interaction effects to influence the progression of CAN.

Correction: Synergistic Effect of Viral Load and Alcohol Consumption on the Risk of Persistent High-Risk Human Papillomavirus Infection

Purpose This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection. Methods Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated. Results Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05–8.18) and 2-year persistence (OR 8.08, CI 2.36–27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89–9.05) and 2-year persistence (OR 6.61, CI 2.09–20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40–6.75 or OR 2.05, CI 0.87–4.83) and 2-year persistence (OR 6.40, CI 1.72–23.8 or OR 4.14, CI 1.18–14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63). Conclusions The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73‒19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61‒27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95‒284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.