Weak Risk Factor Research Articles

Role of hormonal risk factors in oral cancer development

Male: female ratio of oral cancer cases (OC) is fairly high. Lower rate of female cases as compared with males suggests that some endocrine factors may play role in the development of tumors. The aim of the present study was to clarify the differences of risk factors for OC among male and female cases. In the Oral and Maxillofacial Department of Semmelweis University 2660 OC (2130 males and 530 females) patients were included into the study. Ratio of smoking, alcohol consumption, elevated serum glucose level and menopausal data of the female patients were registered. Concordant to the literary data, smoking and excessive alcohol consumption proved to be an important risk factor for OC both among male and female patients. However, moderate alcohol consumption was a weak risk factor among male and no risk factor among female cases. Elevated serum glucose level was not significant OC risk among male cases, but was a high risk factor among female patients, especially in gingival cancer cases. The female OC cases were near exclusively postmenopausal, and the term between the time of menopause and clinical OC diagnosis was fairly long (average: 17 year). These results suggest that estrogen-deficiency may play an important role in the initiation of OC. In the female OC cases menopause appeared in significantly younger age, and the rate of hysterectomy was also significantly higher as compared with the tumor-free control cases. These data also support the estrogen-deficiency theory of cancer initiation. In postmenopausal female patients both estrogen-deficiency and elevated fasting glucose proved to be risk factors for OC. These results reveal new aspects concerning the etiology of OC and give a possible explanation how smoking-associated tumors may develop even without smoking.

Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism

Venous and arterial thromboses have traditionally been considered distinct pathophysiologic entities. However, the two disorders have many features in common, and there is evidence that persons with venous thrombosis may be at greater risk for arterial events. The pathogenesis of both disorders includes endothelial injury, platelet activation, elevated levels of intrinsic clotting factors and inflammatory markers, increased fibrinogen, and impaired fibrinolysis. In addition, older age, obesity, dyslipidemia, and smoking predispose to both venous and arterial thrombosis. While the evidence that arterial disease is a risk factor for venous thrombosis is inconclusive, arterial disease does appear to occur with a modestly increased frequency in patients with a history of venous thromboembolism. Reported odds ratios in such patients were 1.2 for myocardial infarction, 1.3 for stroke, 2.3 for carotid plaque, and 4.3 for coronary calcification. Of note, in persons under age 40 with unprovoked venous thrombosis, the odds ratio for acute myocardial infarction was as high as 3.9. In general, however, venous disease is considered to be a weak risk factor for arterial thrombosis, and the use of agents specifically targeted to the prevention of heart attack or stroke in the majority of persons with VTE cannot be recommended at present.

Combined “pro-atherosclerotic” variants of the ACE and APOE genes increase the risk of the coronary artery disease associated with the presence of cigarette smoking

Objective — Cigarette smoking increases the synthesis of angiotensin-I converting enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo E).Thus we explored the gene-environment interactions between APOE gene epsilon and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary artery disease (CAD) patients.Methods — We analysed 360 subjects: 171 CAD patients and 189 blood donors without a history of cardiovascular diseases. ACE and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, respectively.To determine gene-environment interactions, epidemiological methodology was used.Results — The ACEDD genotype was a rather weak risk factor of CAD in the analysed population (OR = 1.87, P= 0.01).The differences in allele and genotype distribution of the APOE polymorphism were not statistically significant.The carriers of the combined genotype ACEDD + APOEɛ4ɛ4,ɛ3ɛ4,ɛ2ɛ4 were more frequent in patients, however, the differences were on the bound of statistical significance (P= 0.08). Logistic regression analysis showed that the ACEDD + apo Eɛ4ɛ4,ɛ3ɛ4,ɛ2ɛ4 cigarette smokers were much more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P= 0.009).We confirmed these results using the 4 ≈ 2 table approach and we found a synergistic effect of the ACEDD + APOEɛ4ɛ4,ɛ3ɛ4,ɛ2ɛ4 combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09).Conclusions — We demonstrated the existence of the synergistic effect between cigarette smoking and the contemporaneous carrier-state of APOE e4 and ACED alleles which increased the risk of CAD to a large extent.

Genetic Variations and Their Influence on Risk and Treatment of Venous Thrombosis

Venous thrombosis (VT) is a highly prevalent disease. Risk factors can be genetic or acquired. The well-established genetic polymorphisms predisposing to thrombophilic disorders can be divided into rare 'loss-of-function mutations' in anticoagulant proteins and common 'gain-of-function mutations' in procoagulant proteins, which are weaker risk factors. In addition to functional polymorphisms, defects in common pathways affecting biosynthesis or clearance of plasma coagulation factors and their relations to VT risk have been detected. Recently, investigations regarding genetic variations and response to drug treatment, relevant for the pathogenesis as well as therapy of venous thromboembolism have been performed. The methodical advances in genetic research have led to the identification of a number of new variants with still unclear association to VT. This review aims to discuss the established genetic risk factors as well as some candidate predictors of VT. Further, the recent developments in pharmacogenomics are reviewed.

Analysis of UBQLN1 Variants in a Polish Alzheimer’s Disease Patient: Control Series

Late-onset Alzheimer’s disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in UBQLN1 confer a risk for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak association with the rs2781002 polymorphism, however, contrary to the initial reports, in our group the association was with the A allele. Risk estimation for AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD (OR = 1.8, 95% CI = 1.1–3.1, p = 0.025). This effect was stronger in a group of LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an increase of haplotypes with an A allele in the case group. Also, the specific haplotypes with the A allele that increase AD risk differ between the APOE4-positive and APOE4-negative pools. However, the association observed seems to be driven mostly by rare (<5%) haplotypes. Results suggest a need for additional association studies and in silico analysis of the UBQLN1 locus.

Association of NAD(P)H:Quinone Oxidoreductase 1 Polymorphism and Alzheimer’s Disease in Chinese

Several lines of evidence support a role of oxidative stress in the pathology of Alzheimer's disease (AD). NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyzes the two-electron reduction of quinones, preventing their participation in redox cycling and subsequent generation of reactive oxygen species. We examined association between the NQO1 C609T gene polymorphism and sporadic AD in a Chinese population comprising 311 AD patients and 330 controls. Our results showed a higher T-allele frequency in the AD cases compared with the controls. The difference was close to but did not reach statistically significant level [p = 0.059; odds ratio (OR) T versus C = 1.236; 95% confidence interval (95% CI), 0.992-1.540]. A significantly low C/C genotype frequency in the AD cases compared with the controls was detected (p = 0.025; OR C/C versus C/T + T/T = 0.674; 95% CI, 1.049-2.098) and APOE epsilon4 status analysis revealed significant difference in the APOE epsilon4 non-carriers (p = 0.036; OR = 0.633; 95% CI, 1.027-2.427). In the > or =65 years samples, significantly low C/C frequency in the AD cases in comparison with the controls was observed in the APOE epsilon4 non-carriers (p = 0.045; OR = 0.595; 95% CI, 1.010-2.794). These results indicated that the C/C genotype had a possible protective effect against AD development, and the T allele might be a weak risk factor for late onset AD.

Venous Thromboembolism in Trauma Patients

Serial venous duplex scans (VDS) were done in 507 trauma patients with at least one risk factor (RF) for venous thromboembolism (VTE) during a 2-year study period. Deep vein thrombosis (DVT) was detected in 31 (6.1%) patients. This incidence was 3.1 per cent in low (1-2 RFs), 3.4 per cent in moderate (3-5 RFs), and 7.7 per cent in high (> or =6 RFs) VTE scores (P = 0.172). Incidence was statistically different (3% vs. 7.2%, P = 0.048) on reanalyzing patients in two risk categories, low-risk (1-4 RFs) and high-risk (> or =5 RFs). Only 4 of 16 RFs had statistically higher incidence of DVT in patients with or without RFs: previous VTE (27.3% vs. 5.6%, odds ratio (OR) 6.628, P = 0.024), spinal cord injury (22.6% vs. 5%, OR 5.493, P = 0.001), pelvic fractures (11.4% vs. 5.1%, OR 2.373, P = 0.042), and head injury with a greater than two Abbreviated Injury Score (10.5% vs. 4.2%, OR 2.639, P = 0.014). On reanalyzing patients with > or =5 RFs vs. <5RFs, obesity (14.3 vs. 6.1%, P = 0.007), malignancy (5.6% vs. 0.6%, P = 0.006), coagulopathy (10.8% vs. 1.8%, P = 0.000), and previous VTE (3.2% vs. 0%, P = 0.019) were significant on univariate analysis. Patients with DVT had 3.70 +/- 1.75 RFs and a 9.61 +/- 4.93 VTE score, whereas, patients without DVT had 2.66 +/- 1.50 RFs and a 6.83 +/- 3.91 VTE score (P = 0.000). DVTs had a direct positive relationship with higher VTE scores, length of stay, and number of VDS (>1 r, P < or = 0.001). Increasing age was a weak risk factor (0.03 r, P = 0.5). First two VDS diagnosed 77 per cent of DVTs. Patients with injury severity score of > or =15 and 25 had higher DVTs compared with the ones with lower injury severity score levels (P < or = 0.05). Pulmonary embolism was silent in 63 per cent and DVTs were asymptomatic in 68 per cent.

Family History of Asthma and Atopy: In-depth Analyses of the Impact on Asthma and Wheeze in 7- to 8-Year-Old Children

Development of asthma in children is influenced by interactions between genetic and environmental factors. It is unclear whether paternal or maternal histories of disease confer different risks. Previous population-based studies have not stratified analyses by child gender and sensitization status. Our aim was to study in detail the hereditary component of childhood asthma. A population-based cohort of 3430 (97% of invited) 7- to 8-year-old school children participated in an expanded International Study of Asthma and Allergy in Childhood survey, and two thirds were skin-prick tested. Heredity was defined as a family history of (1) asthma and (2) atopy (allergic rhinitis or eczema). Multivariate analyses corrected for known risk factors for asthma. At ages 7 to 8, prevalence of asthma was 5.3% among the children and 9.0% among the parents. In children without parental asthma or parental atopy, the prevalence of asthma was 2.8%. Corrected for parental asthma, parental atopy was a weak but significant risk factor. There were minor differences in the impact of parental disease between sensitized and nonsensitized children and between boys and girls. As risk factors for childhood asthma, there were major differences between parental asthma and parental atopy. Sibling asthma was only a marker of parental disease. Interactions between parental disease and the child's allergic sensitization or gender were not statistically significant. Asthma in both parents conferred a multiplicative risk, whereas the effect of parental atopy was additive, however limited. Asthma and atopy, despite their causal relationship, are separate entities and could be inherited differently. This large, population-based, and well-characterized cohort study does not confirm parent-of-origin effects found in previous studies.

The influence of the age in the risk of the prothrombin G20210A mutation for spontaneous venous thrombosis

Factor V Leiden mutation (FVL), and the prothrombin G20210A mutation (PT G20210A) are polymorphisms with a weak risk factor for venous thromboembolic disease. The probability of spontaneous venous thrombosis in carriers of thrombophilic mutations (FVL and PT G20210A) was analyzed. We studied 735 individuals (407 were healthy controls and 328 patients with venous thrombosis) with respect to FVL and PT G20210A, determined by polimerase chain reaction in liquid phase, real time. chi2 test and logistic regression analysis were used to evaluate the results. The dates were analyzed with the statistical program SPSS v. 14.0. The carrier patients of PT G20210A mutation whose age was over 40 years had a risk factor for spontaneous venous thrombosis which was 9.28 (odds ratio [OR]) (95% confidence interval [CI], 3.01-28.60; p < 0.0005) times greater than carriers of the PT G20210A mutation who were 40 year-old or younger. In our patients, being male meant a weak risk factor for venous spontaneous thrombosis (p = 0.021; OR = 1.64; 95% CI, 1.08-2.51) . Our results demonstrate a potentiation of the thrombotic risk by an increase of age in the carriers of the PT G20210A mutation.

Challenges in obesity epidemiology

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO; published with permission Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1) , 1–11 1 obesity reviews (2007) 8 (Suppl. 1) , 1–11 OnlineOpen: This article is available free online at www.blackwell-synergy.com Blackwell Publishing LtdOxford, UKOBRObesity Reviews1467-7881© 2007 Queen’s Printer and Controller of HMSO; published with permission; Journal compilation © 2007 The International Association for the Study of Obesity ? 20078 ••111Review Article Challenges in obesity epidemiology D. Canoy & I. Buchan

Drunk, drowsy, doped: skiers' and snowboarders' injury risk perceptions regarding alcohol, fatigue and recreational drug use

The objective was to investigate perceptions of snowfield resort visitors about injury risk regarding alcohol, fatigue and recreational drug use. Visitors to a resort village in a large Australian snowfield region completed a brief survey about fatigue, alcohol and recreational drug use and injury risk perception. Participants stated their ability to ski or snowboard and drive safely following a lack of sleep, alcohol and recreational drug use. Intoxicated snowfield resort visitors were compared with non-intoxicated visitors. Safety beliefs across snow sport and transport were compared. Participants reported that they generally slept less than usual and 30% reported both drinking alcohol and using drugs more than usual while visiting the snowfields. Participants perceived driving as a greater injury risk than skiing/snowboarding (p < 0.001). Fatigue was perceived as a relatively weak injury risk factor, particularly whilst skiing and snowboarding. Awareness needs to be raised among snowfield resort visitors about the contribution of alcohol, fatigue and recreational drug use to snow sport and transport-related injury risk.

Thrombospondin-4 1186G>C (A387P) is a sex-dependent risk factor for myocardial infarction: A large replication study with increased sample size from the same population

Case-control studies have successfully identified many genetic associations for complex diseases but suffer from lack of reproducibility in the same population. Demonstrating weak genetic effect requires large sample sizes to minimize statistical bias. Based on a study examining 500 myocardial infarction (MI) patients and 500 controls from the genetically isolated Newfoundland population, we previously reported that thrombospondin-4 (THBS-4) 1186G>C variant associates with MI in women. To validate this sex-dependent association with the THBS-4 variant, we analyzed an additional 532 patients and 514 controls from the same population and the combined cohort consisting of 1032 patients and 1014 controls. Genotyping of THBS-4 1186G>C was conducted using Taq Man 1186G>C (A3879P) (rs 1866389) genotyping technology on real-time polymerase chain reaction. The genotype distributions of THBS-4 1186G>C in the validation and combined cohorts were similar with those in our initial study, which supports genetic homogeneity in the studied population. The association of the CC genotype with MI in women (odds ratio [OR], 2.96; P = .008) reported in our initial cohort failed to achieve statistical significance in our validation cohort (OR, 1.53; P = .307) but was confirmed in the combined cohort (OR, 2.14; P = .009). In contrast to the results from the initial cohort was a significant association of the CC genotype with later onset MI in the validation (OR, 2.37; P = .029) and combined cohorts (OR, 2.22; P = .011). Moreover, the larger studied population gave statistical power to associate the CC genotype with risk of MI in the total patient population (OR, 1.58; P = .023). Homozygosity for the THBS-4 1186C variant is a weak risk factor for MI especially in older women.

The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease

The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. To establish risk factors of PTS and its impact on venous thrombotic disease. We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.

Associations of Birthweight and Maternal Fertility Problems with Childhood Cancers.

Higher birthweight, maternal history of miscarriage and low birth order have been associated with increased risk of childhood leukaemias and some solid tumours. No study has investigated these factors together and differences in disease etiology between girls and boys have been generally overlooked. In a retrospective case-control study, 732 childhood (≤15 yr) cancer cases from the population-based Northern Region Young Persons' Malignant Disease Registry (NRYPMDR) whose hospital birth records could be accessed and 3723 controls matched for date and hospital of birth were compared. We examined maternal reproductive history and birthweight for gender-specific associations using conditional logistic regression. In univariate analysis, maternal history of miscarriage showed an association with all cancers (OR = 1.29; 95% CI = 1.05 to 1.62, P = 0.02). In individual cancer groups, this association was significant for acute lymphoblastic leukaemia (ALL) (n=225, OR = 1.56; 95% CI = 1.07 to 2.27, P = 0.02), and marginally significant in osteosarcoma and neuroblastic tumours (neuroblastoma and ganglioneuroblastoma). There was no significant association with birth order. Being first born was a weak risk factor for ALL in boys only (OR=1.3, 95% CI = 0.8 to1.8). In boys but not in girls, the risk of ALL increased with birthweight (OR = 1.06 per 100 gr increase; 95% CI = 1.01 to 1.11, P = 0.01). When birthweights were normalized using UK standards for gestational age and gender, the associations were not more marked. A multivariate model for ALL confirmed the independence of associations with miscarriage history and birthweight. Gestational age was not a risk marker and did not explain the associations with birth weight and miscarriage history. Consideration of gender unravelled significant associations of maternal reproductive history and size at birth with childhood cancer markedly different between girls and boys. Most notably, associations with birth weight and miscarriage and the weak association with being first-born in childhood ALL were all stronger in males. The findings for birthweights normalized for gestational age suggested that size at birth rather than in utero growth trajectory is of etiologic importance in childhood ALL.

Production of Tissue Factor Pathway Inhibitor in Endothelial Cell Cultures Is Reduced by Estrogens, Selective Estrogen Receptor Modifiers, and a Selective Estrogen Receptor Downregulator.

Low plasma tissue factor pathway inhibitor (TFPI) is a weak risk factor for venous and arterial thrombotic disease. Female hormones strongly influence the level of TFPI in plasma. Oral contraceptives (OC) and hormone replacement therapy (HRT) reduce plasma levels of TFPI by 30–50%, and premenopausal women have lower TFPI than postmenopausal women and men. Moreover, the selective estrogen receptor modifiers (SERM) Tamoxifen and Raloxifen also reduce TFPI in plasma. The effect of these drugs on TFPI may in part explain their prothrombotic effects. The aim of the current study was to study the effects of estrogens and SERMs on the production of TFPI from endothelial cell cultures. Human coronary arterial endothelial cells from Cambrex Bio Science were seeded into 24 well plates and preincubated with 0 (control) or 10 nM of 17β-estradiol (E2), 17α-etinyl-estradiol (EE2), tamoxifen or raloxifene for 48 hours. The cell-medium was then changed and the cells were stimulated with the same concentrations of the same drug for 24 hours before harvesting. TFPI total antigen was measured using a commercial ELISA-kit, and cellular total protein was measured by an improved Lowry assay. The concentration of TFPI total antigen was normalized against the concentration of total protein from the cells. We found that 10 nM of E2, EE2, Tamoxifen and Raloxifene reduced TFPI in the cell medium with 39% (E2), 30% (EE2), 19% (Tamoxifen), and 35% (Raloxifene) compared to untreated cells. Fulvestrant is a selective estrogen receptor downregulater (SERD) known to have no agonist effects, and is also used as a drug against breast cancer. The effect of fulvestrant on TFPI-production was tested in order to later use it as a blocker of the estrogen receptor (ER), to decide whether the effects observed from the other compounds were ER-dependent. Surprisingly, 10 nM fulvestrant reduced TFPI in the cell medium by 12%, and 1000 nM fulvestrant reduced TFPI by 30%. We conclude that the effects of estrogens and SERMs, and interestingly also the SERD fulvestrant, reduce TFPI production in endothelial cells. Based on these results we propose that women using fulvestrant as a drug against breast cancer will have reduced levels of TFPI, and perhaps also increased risk for thrombotic dieseases.

Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the literature

Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of pediatric uveitis in Europe and North America. Uveitis is commonly perceived as a frequent sequela of JRA and JRA-associated uveitis is commonly considered to have a complicated course with frequent adverse visual outcomes. We performed a systematic literature search for series of consecutive patients with JRA (as defined by the American College of Rheumatology criteria) reporting on the frequency of uveitis and/or complications of uveitis, published between January 1980 and December 2004. The main outcome measures were: the cumulative incidence of uveitis in JRA, the cumulative incidence of adverse visual outcome and that of complications in JRA-associated uveitis. Additionally, the influence of gender, presence of antinuclear antibody (ANA) and disease onset subtype to the likelihood of developing uveitis were examined. Analysis of pooled data from the 26 eligible series suggested a cumulative incidence of uveitis in JRA of 8.3% [95% confidence intervals (CI), 7.5-9.1%]. The cumulative incidence of uveitis varied according to geographic location, being highest in Scandinavia, then the US, then Asia and lowest in India. JRA-associated uveitis was more common in pauciarticular than polyarticular onset patients [odds ratio (OR) = 3.2, 95% CI, 2.33-4.36] and in ANA-positive than ANA-negative patients (OR = 3.18, 95% CI, 2.22-4.54). Female gender was only a weak risk factor for the development of uveitis in JRA patients (OR = 1.69, 95% CI 1.09-2.62) and was not statistically significant after considering disease onset subtypes. In JRA-associated uveitis the cumulative incidence of cumulative incidence of adverse outcome (visual acuity < 20/40 OU) was 9.2% (95% CI: 4.7-15.8) of cataracts 20.5% (95% CI: 15.5-26.3), of glaucoma 18.9% (95% CI: 14.4-24.2) and of band keratopathy 15.7% (95% CI: 10.9-21.7). The cumulative incidence of uveitis in JRA varies according to geographic location, presence of ANA, type of JRA onset and gender. Uveitis, adverse visual outcome, and complications in JRA are less frequent than commonly accepted.

The first ambulatory screening on thromboembolism: a multicentre, cross-sectional, observational study on risk factors for venous thromboembolism.

To assess the prevalence of risk factors for venous thromboembolism (VTE) and the prevalence of recent (<1 year) VTE [including superficial vein thrombosis (SVT), deep vein thrombosis (DVT) and pulmonary embolism (PE)] amongst patients attending general practitioner (GP) surgeries. Multicentre, cross-sectional, observational study. A total of 1536 GP surgeries. A total of 15 180 adult, co-operative subjects, who had consulted their GP for a health disorder and signed the informed consent form. None. Prevalence of known VTE risk factors graded according to importance and prevalence of recent (<1 year) VTE events (including SVT), based on interviews. About 1:5 patients had at least one strong risk factor and about 1:20 had at least two risk factors, with no difference between sexes. The prevalence of strong risk factors increased with age. Most were related to medical conditions: history of SVT and/or DVT/PE, heart failure and malignancy. About 3:4 women and 2:3 men had at least one moderate to weak risk factor; nearly 1:2 women and 1:3 men had at least two moderate to weak risk factors. The most common were: history of VTE, smoking, history of miscarriage, estrogen therapy, obesity, and varicose veins. Overall, 80% women and 67% men had at least one risk factor, and 50% women and 35% men had at least two risk factors. The prevalence of recent (<1 year) VTE was 3.4% in women and 2.4% in men, and increased with age. The majority of cases were SVT in both sexes (2.5% in women and 1.5% in men). The prevalence of risk factors for VTE amongst patients attending GP surgeries is high. GPs should bear this in mind during their daily practice.

Individual and population risk of drug use among adolescents attending an English Youth Offending Team: An epidemiological approach

This study aims to show how epidemiological methods can help service providers and policy makers to understand how risk factors for drug use differ at individual and population levels. The study sample comprised 180 young people referred to the Wolverhampton Youth Offending Team, of whom 99 (55%) had never used drugs, 35 (19%) used drugs occasionally (less than weekly) and 46 (26%) used drugs regularly. The probability of an individual's drug use was determined for each of the 64 combinations of the six risk factors in the final multivariate model. An individual with all six risk factors has a 78% chance of being a regular user, a 21% chance of being an occasional user and a 0% chance of being a non-user. These findings do not require assumptions regarding causality; they simply express the relationship between respondents' characteristics and their probability of being a drug user. Policy makers need to be able to combine this information with the relative occurrence of risk factors in the population. Furthermore, they need to be able to make an assessment of the causal status of risk factors in relation to drug use. Variables such as familial drug use are high risk factors for individuals (adjusted OR: 22), but are relatively uncommon in the population (6%). In contrast, current smoking is a relatively weak risk factor for individuals (adjusted OR: 4), but occurs more frequently in the population (32%). After adjusting for multiple risk exposures using the appropriate formulae, the population attributable risk (PAR) for familial drug use is 27% compared to 64% for smoking. While we advocate caution in relation to causality, the current analyses provide the first estimates of how exposure to risk can predict individual and population risk of drug use in a vulnerable population. Given the extensive literature on risk factors for drug use, it should be possible to apply epidemiological methods to other data sets in the field of drug addiction.

The frequency of GSTT1 null genotype in Turkish population and lung cancer risk

BACKGROUND : Previous studies have suggested that Glutathione S -transferase (GST) genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In different ethnic groups variations in null allele frequency has been observed. AIMS: We aimed to evaluate whether genetic polymorphisms of Glutathione S -transferase theta (GSTT1) influence individual susceptibility to lung cancer in Turkish population. We tried to clarify the frequencies of GSTM1 gene polymorphisms in a Turkish population. METHODS: DNA samples, extracted from the whole blood were amplified using polymerase chain reaction (PCR) method in all of the 68 cases, composed of 31 previously diagnosed lung cancer and 37 healthy controls. RESULTS: The prevalence of GSTT1 null genotype in the lung cancer patients was 29%, compared to 11% in control group. GSTT1 null genotype was found to be higher in cancer group compared to the control group, although it was not statistically significant (OR = 3.37, 95% CI = 0.92-12.32, P = 0.06). There was also no significant relation in GSTT1 genotypes among histopathology types of lung cancers. The frequency of GSTT1 was found to be 25.4% ( n = 952) when the studies of Turkish population were reviewed. CONCLUSION: It can be concluded that carrying the GSTT1 null genotype may be accepted as a weak risk factor for the susceptibility to lung cancer.

Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50

We have investigated the occurrence of basal cell carcinoma (BCC) in relation to a number of single nucleotide polymorphisms (SNPs) in the chromosomal region 19q13.2-3. A case–control study including 322 basal cell carcinoma cases and a similar number of controls was nested in a population-based prospective investigation encompassing 57,053 Danes (aged 50–64 at inclusion) living in Copenhagen or Aarhus in Denmark. We found that the polymorphism XPD Arg156Arg was associated with risk of basal cell carcinoma (rate ratio (RR) = 1.59, 95% confidence interval (CI) = 1.02–2.50 for homozygous carriers of the A-allele), and that the association was strongest in the youngest age interval of the study group (50–55 years) (RR = 2.33, 95% CI = 1.03–5.28). The polymorphisms XPD Asp312Asn and XPD Lys751Gln were not associated with risk of basal cell carcinoma. While it cannot be ruled out that the present findings are due to chance, the present results are consistent with previous findings that XPD Arg156Arg is a weak risk factor for basal cell carcinoma.