Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population.

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14-1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44-0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM.

Surveillance of chronic noninfectious diseases.

Surveillance is a comprehensive system of epidemiological work involving continuous collection, analysis and distribution of data on all characteristics of the disease. Among health professionals, surveillance in connection with noninfectious diseases is not as known as in infections where it has clearly proven successful. The principle of epidemiological surveillance may be applied in chronic noninfectious diseases but certain pitfalls and differences between this category and infectious diseases need to be borne in mind. These diseases have multifactorial etiology; their development is contributed to by several risk factors, mainly those associated with lifestyle; they have a long preclinical period with no apparent problems; data on their prevalence in populations may vary depending on the definition and diagnostic criteria used. Epidemiological surveillance as a continuous process aids in understanding the extent of the risk of a disease in a population, contributes to provision of early and effective care and control over their prevalence. The paper aims to describe the specific aspects of surveillance in chronic noninfectious diseases.

Total and high-molecular-weight adiponectin levels and prediction of insulin resistance.

INTRODUCTION: Adiponectin is a peptide secreted by adipocytes; its reduction is associated with obesity-related disorders, including insulin resistance (IR). The study analysed levels of total adiponectin and its high-molecular-weight (HMW) oligomer in a group of metabolically healthy adults and in patients with type 2 diabetes mellitus (T2DM) to evaluate these levels as potential predictors of the presence of IR. MATERIALS AND METHODS: The study comprised 269 metabolically healthy adults and 300 patients with T2DM. Anthropometric and bio-chemical indices were measured, including total and HMW adiponectin levels; the Homeostatic Model Assessment of IR (HOMA-IR) index was calculated, and logistic regression analysis was used to predict the presence of IR. RESULTS: In healthy individuals, both total and HMW adiponectin levels were significantly higher than in diabetic patients. Total and HMW adiponectin levels were moderately correlated with the HOMA-IR index. Logistic regression analysis showed that increased levels of both total adiponectin (odds ratio [OR] 0.598, 95% confidence interval [CI] 0.483-0.723) and the HMW form (OR 0.360, 95% CI 0.242-0.511) are protective factors for the development of IR. The cut-off levels were 4.22 mg/L for total adiponectin and 2.75 mg/L for HMW adiponectin. The results are valid for middle-aged European adults. CONCLUSIONS: Adiponectin levels below the indicated cut-offs may predict a potential risk for the development of IR.

Risks and protective factors for triple negative breast cancer with a focus on micronutrients and infections.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer (BC) with a poor prognosis. Second, patients cannot benefit from targeted therapy, except for those with BRCA1/2 mutations, for whom poly (ADP-ribose) polymerase (PARP) inhibition therapy using olaparib has recently been approved. As global priorities continue to be epidemiological analysis of BC risk factors and early diagnosis, this review focuses on the risks and protective factors associated with TNBC. A PubMed keyword search for new knowledge on the risks and protective factors for TNBC was carried out. We also found statistical information from current online databases concerning the estimated incidence, prevalence and mortality worldwide of this cancer. Traditional risk factors for BC and TNBC are those related to reproduction such as the age of menarche, age of first birth, parity, breastfeeding and age at menopause. Attention needs to be paid to familial BC, weight control, alcohol consumption and regular physical activity. Epidemiological studies on TNBC provide evidence for protective factors such as regular consumption of soya, seafood, green tea, folic acid and vitamin D. Potential risk factors may include night work and viral infectious agents like human papillomavirus (HPV) and Epstein-Barr virus (EBV). Droplet digital methylation-specific PCR (ddMSP) is a possible new screening method for detection of BC including TNBC. Further research is necessary to validate these new factors.

Refractory Ventricle Arrhythmias Alternating with Pulseless Electrical Activity in a Young Woman Rescued by Extracorporeal Cardiopulmonary Resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA). CASE PRESENTATION: The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator. CONCLUSION: Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.

A study evaluating noise levels at selected schools in the Czech Republic.

OBJECTIVE: Worldwide, primary schools are the most important segment of childhood education. The main disturbing source of noise in schools is human speech, the primary component of the learning process. School noise has a negative impact on information processing, teachers and pupils, and communication in the classroom. The study aimed at assessing A-weighted sound pressure levels in primary school classrooms. It was concerned with A-weighted sound pressure levels and their fluctuation during various classes. METHODS: The noise was measured with the static calibrated Brüel and Kjær 2260 Investigator sound level meter. The sound pressure levels were measured twice in 12 classes as 11 different subjects were taught to reduce the uncertainty of results due to their potential variability in time. From the instantaneous values, LA (t), equivalent continuous A-weighted sound pressure levels (LAeq,T) and LAmax were calculated. RESULTS: The mean equivalent A-weighted sound pressure level during lessons irrespective of age and subjects taught was 68.0 ± 3.4 dB (uncertainty of measurement). The highest levels of noise were in physical education and arts; the lowest levels were found for English taught as a foreign language. There were no statistically significant differences in LAeq,T depending on the numbers of children in the classes. The main source of noise is pupils. Attention should be paid to negative feelings of noise to reduce LAeq,T in schools. CONCLUSIONS: Continuous noise pollution, in combination with stress and the mentally demanding nature of the teaching profession, may lead to numerous negative effects on human personality.

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma.

Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.

Experiences with preventing carpal tunnel syndrome in an automotive plant.

OBJECTIVES: Carpal tunnel syndrome (CTS) is a common occupational disease. The aim was to assess the effect of preventive measures in automotive assembly workers. MATERIAL AND METHODS: The analysis summarizes data from annual crosssectional studies. The 7-year analysis of data was based on medical records obtained from an occupational physician and inspections carried out at the workplace where targeted preventive measures were introduced, including better ergonomic arrangement of the workplace, technical adjustments facilitating the work, preventive nerve conduction studies (NCS) testing of the median nerve once a year, switching of workers and their targeted rotation within the workplace. The NCS testing of median nerve conduction at the wrist was the basic objective method for assessment of the prevalence and severity of CTS. Over the study period, the sample comprised 1804 workers at risk for repetitive overuse of the upper extremities, of whom 281 were females with a mean age of 38.5 years and 1523 were males with a mean age of 31.4 years. RESULTS: Over the study period, a total of 13 cases of CTS were recognized as an occupational disease in the plant, 8 of which occurred within the first 2 years from the initiation of production. Introduction of preventive measures decreased the prevalence of median neuropathy from 18.3% of examined extremities in 2011 to 10.5% in 2013 (p = 0.003). In early 2014, the production pace increased and this was accompanied by a rise in abnormal NCS findings to 16.9%. Over the study period, the rate of sensorimotor neuropathy decreased in favor of merely sensory neuropathies, which have been most frequent since 2013. The percentage of employees whose contracts were terminated due to median neuropathy decreased steadily from 5.5% to 0.4%. CONCLUSIONS: Targeted prevention of work-related CTS is effective as evidenced by the decrease in the prevalence of median neuropathy detected by NCS. Int J Occup Med Environ Health 2017;30(1):45-54.

Primary and secondary prevention of colorectal cancer in the Czech Republic.

Colorectal cancer is one of the most frequent malignancies in the Czech Republic and worldwide. Also, a high prevalence of overweight and obesity, a high proportion of smokers in the population, and one of the highest per capita alcohol consumption rates are typical for the Czech population. The role of general practitioners in the prevention of colorectal cancer is crucial. In primary prevention, the doctor should emphasise the importance of a healthy lifestyle - a balanced diet rich in fruits and vegetables, maintaining a normal body weight, adequate physical activity, and non-smoking. In secondary prevention, patients should be informed about the possibilities of colorectal cancer screening and the benefits of early detection of the disease. Participation rates of the target population for colorectal cancer screening are low. Steps leading to increased participation in colorectal cancer screening (including postal invitations) play an important role in influencing the mortality of colorectal cancer.

Total and High Molecular Weight Adiponectin Levels and Prediction of Cardiovascular Risk in Diabetic Patients.

The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients.

In vitro efficacy of synthetic skin repellent IR3535 on head lice (Pediculus capitis).

In in vitro tests, skin repellent IR3535, applied in the form of the Diffusil H Prevental product in an aerosol bomb (active compound 20%), killed 100% of head lice (females and males) and nymphs 2 and 3, when directly sprayed at a dose of 0.94 mg of the active compound per square centimeter. Crawling lice exposed for 1 min on the filter paper impregnated by the same concentration showed no effort to suck blood 30 min after exposition. Twenty hours later, their mortality rate was 11 %. After the lice had been exposed for approximately 1 min (until they actively left the area) on 5 cm round areas of skin of test persons treated with the repellent at a mean total dose of 23.3 mg of active compound, they showed no effort to suck blood on the clean skin of other test person either immediately after exposure or 30 min later. Their mortality after 20 h ranged from 59 to 16%, depending on the time elapsed from skin treatment (10 min to 27 h).

[Antimalarial prophylaxis in travelers to malaria risk areas]. / Antimalarická profylaxe pri cestách do zahranicí

Malaria is one of the most common diseases imported to the Czech Republic with an upward trend in incidence. Travelers are leaving for abroad without antimalarial prophylaxis or refuse preventive antimalarial drugs. Failure to comply with antimalarial prophylaxis in high-risk areas can lead to malaria infection which may manifest itself even after returning home. As the disease is often mistaken for influenza, any traveler to malaria risk areas who presents with fever needs to be tested for malaria. Individual preventive measures consist in the correct use of repellents, insecticides, and bed nets LLITNs, wearing light colored clothing, and regular use of antimalarial prophylaxis.

Xenobiotic metabolizing gene variants and renal cell cancer: a multicenter study.

BACKGROUND: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. METHODS: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case-control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H: quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. RESULTS: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. CONCLUSION: We observed no association between this pathway and renal cell cancer.

Renal cancer risk and occupational exposure to polycyclic aromatic hydrocarbons and plastics.

OBJECTIVE: To investigate whether occupational exposure to polycyclic aromatic hydrocarbons and certain plastic monomers increased renal cell carcinoma (RCC) risk. METHODS: Unconditional logistic regression was used to calculate RCC risk in relation to exposure. RESULTS: No association between RCC risk and having ever been occupationally exposed to any polycyclic aromatic hydrocarbons or plastics was observed. Duration of exposure and average exposure also showed no association with risk. Suggestive positive associations between RCC risk and cumulative exposure to styrene (P-trend = 0.02) and acrylonitrile (P-trend = 0.06) were found. Cumulative exposure to petroleum/gasoline engine emissions was inversely associated with risk (P-trend = 0.02). CONCLUSIONS: Results indicate a possible association between occupational styrene and acrylonitrile exposure and RCC risk. Additional studies are needed to replicate findings, as this is the first time these associations have been reported and they may be due to chance.

Occupational exposure to arsenic, cadmium, chromium, lead and nickel, and renal cell carcinoma: a case-control study from Central and Eastern Europe.

OBJECTIVES: To investigate the risk of renal cell carcinoma (RCC) in Central and Eastern Europe in relation to exposure to known and suspected carcinogenic metals. METHODS: During 1999-2003, the authors conducted a hospital-based study in Czech Republic, Poland, Romania and Russia, including 1097 cases of RCC and 1476 controls. Occupational exposure to arsenic, cadmium, chromium(III), chromium(VI), lead and nickel was assessed by teams of local industrial hygiene experts, based on detailed occupational questionnaires. RESULTS: The ORs for RCC were 1.55 (95% CI 1.09 to 2.21) for exposure to lead and 1.40 (95% CI 0.69 to 2.85) for exposure to cadmium. No clear monotonic exposure-response relation was apparent for either duration of exposure or cumulative exposure to either metal, although the OR for the highest category of cumulative exposure to lead was 2.25 (95% CI 1.21 to 4.19). Exposure to other metals did not entail an increased risk of RCC. CONCLUSIONS: For cadmium, the lack of statistical significance of most results, potential confounding and the absence of clear dose-response relations suggest that an association with RCC is unlikely to be causal. In the case of lead, however, the elevated risk in the category of highest cumulative exposure is noteworthy and justifies further investigation.

Adipocyte fatty acid binding protein and C-reactive protein levels as indicators of insulin resistance development.

BACKGROUND: Adipocyte fatty acid-binding protein (aFABP) has recently been identified as a potential circulating marker for metabolic syndrome. C-reactive protein (CRP), a sensitive marker of inflammation, is increased in individuals with diabetes and metabolic syndrome due to the development of subclinical inflammation. The study uses logistic regression models to analyze the relations between aFABP and CRP along with other parameters of insulin resistance. The objective was to investigate the potential use of aFABP and CRP levels as tools in the diagnosis of the metabolic syndrome. METHODS AND RESULTS: The following groups were studied: healthy individuals (A, n=122), obese individuals (B, n=213) and patients diagnosed with metabolic syndrome (C, n=79). Obese persons in Group B had parameters suggestive of early insulin resistance: hypertension, hyperglycaemia, QUICKI (0.305) and higher aFABP levels as compared with the healthy subjects. Group C individuals were diagnosed with metabolic syndrome, as evidenced by the QUICKI markers for insulin resistance (0.293), high aFABP levels (35.3 mg/l). CRP concentrations were lowest in Group A healthy individuals (0.67 mg/l), higher in Group B obese subjects (2.65 mg/l) and highest in Group C patients with metabolic syndrome (3.62 mg/l). Logistic regression models showed an association of aFABP and CRP with BMI (OR 1.12 and 1.39, compared Group A vs C). An association of aFABP and CRP with the QUICKI index showed OR 1.48 and 1.37 (Group A vs C); with triglyceride levels showed OR 1.68 and 1.52 (Group A vs C). An association of aFABP and CRP with glycaemia showed OR 1.48 and 1.51 (Group A vs C), with insulinaemia showed OR 1.44 and 1.38 (Group A vs C) respectively. CONCLUSIONS: AFABP levels were higher in obese individuals and highest in those with metabolic syndrome. CRP concentrations were increased in obese persons whereas individuals with metabolic syndrome were found to have high-risk CRP levels. Logistic regression models showed an association of aFABP and CRP with BMI as well as an association of aFABP and CRP with parameters of insulin resistance, namely the QUICKI index, triglyceride levels, glycaemia and insulinaemia. Both methods are of diagnostic benefit for predicting metabolic syndrome, especially in previously untreated patients.

Genetic syndromes associated with renal cell carcinoma: a review.

AIMS: A review of recent knowledge on heredital syndromes related to renal cell carcinoma. METHODS: Aim of this review was to summarize the recent knowledge of genetic syndromes associated with renal cell carcinoma. RESULTS: Summary of incidence and factors modulating risk of hereditary renal cell carcinoma development. CONCLUSIONS: Hereditary forms of RCC are relatively rare. Their study is beneficial in many ways. In individuals at a higher risk of a hereditary syndrome, the knowledge of hereditary forms may help to significantly decrease the impact of the hereditary disease. In the general population, knowledge acquired by the study of hereditary forms of RCC may in the future contribute to both diagnosis and treatment of sporadic tumours.

Occupational trichloroethylene exposure and renal carcinoma risk: evidence of genetic susceptibility by reductive metabolism gene variants.

Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.

Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

Multiple ADH genes are associated with upper aerodigestive cancers.

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.