Unconditional Regression Analysis Research Articles

Association of Prevotella intermedia with oropharyngeal cancer: A patient-control study

ObjectiveTo investigate the frequencies and bacterial load of three species of periodontal bacteria in samples from oropharyngeal cancer patients versus healthy individuals. Study designThis is a case-control study based on biopsies collected from tumor tissues obtained from patients with oropharyngeal squamous cell carcinoma between 2016 and 2017 and shed oral mucosal epithelial cells that were collected from controls using the Cepimax® brush, carrying out several brushings towards the posterior third edge of the tongue and the cheek. Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia detection and absolute quantification was determined through q-PCR. Statistical analysis included a U- test, X2, Fisher's exact test, odds ratio (OR) and Conditional logistic regression analysis and unconditional regression analysis (p < 0.05). ResultsA total of 48 donors older than 55 years old participated in this study. The population was distributed into 24 patients (cases) and 24 controls. A robust association was established in cases and controls with significance regarding Prevotella intermedia (OR: 15.00) and Porphyromonas gingivalis (OR:11.00). In the comparison between the amount of each bacteria in the groups, P. intermedia showed a higher bacterial load in oropharyngeal cancer patients (p = 0.04). However, multivariate analysis adjusted to the presence of different bacteria and the diverse confounding variables did not reveal significant differences for oropharyngeal cancer association. ConclusionP. gingivalis and P. intermedia were detected more frequently in the group of patients with cancer. The bivariate analysis of the bacterial load evidenced significant differences for Prevotella intermedia, suggesting that it could be associated with oropharyngeal cancer.

A critical analysis of the MOBI-Kids study of wireless phone use in childhood and adolescence and brain tumor risk.

The MOBI-Kids case-control study on wireless phone use and brain tumor risk in childhood and adolescence included the age group 10-24 years diagnosed between 2010 and 2015. Overall no increased risk was found although for brain tumors in the temporal region an increased risk was found in the age groups 10-14 and 20-24 years. Most odds ratios (ORs) in MOBI-Kids were <1.0, some statistically significant, suggestive of a preventive effect from RF radiation; however, this is in contrast to current knowledge about radiofrequency (RF) carcinogenesis. The MOBI-Kids results are not biologically plausible and indicate that the study was flawed due to methodological problems. For example, not all brain tumor cases were included since central localization was excluded. Instead, all brain tumor cases should have been included regardless of histopathology and anatomical localization. Only surgical controls with appendicitis were used instead of population-based controls from the same geographical area as for the cases. In fact, increased incidence of appendicitis has been postulated to be associated with RF radiation which makes selection of control group in MOBI-Kids questionable. Start of wireless phone use upto 10 years before diagnosis was in some analyses included in the unexposed group. Thus, any important results demonstrating late carcinogenesis, a promoter effect, have been omitted from analysis and may underestimate true risks. Linear trend was in some analyses statistically significant in the calculation of RF-specific energy and extremely low frequency (ELF)-induced current in the center of gravity of the tumor. Additional case-case analysis should have been performed. The data from this study should be reanalyzed using unconditional regression analysis adjusted for potential confounding factors to increase statistical power. Then all responding cases and controls could be included in the analyses. In sum, we believe the results as reported in this paper seem uninterpretable and should be dismissed.

Occupational exposure to glyphosate and risk of lymphoma:results of an Italian multicenter case-control study

BackgroundThe International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy.MethodsThe Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011–17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre.ResultsVery few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10− 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL.ConclusionsOur findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

Case-control study on risk factors for upper respiratory tract infection in hospitalized children with mental disorders

Objective To investigate the clinical characteristics of upper respiratory tract infection in hospita-lized children with mental disorders, and to analyze the risk factors for nosocomial infection, so as to provide reference for clinical treatment and prevention and control of nosocomial infection(NI). Methods The NI of 1 587 hospitalized children at the Second Affiliated Hospital of Xinxiang Medical University from January to December 2016 was investigated and a retrospective study was conducted on 78 hospitalized children with nosocomial upper respiratory tract infection.In a ratio of 12, the patients with mental disorders during the same time at hospital, without the occurrence of hospital infection, with same gender and same age group, were selected as the control group, then the univariate regression analysis and multivariate conditional Logistic regression analysis were carried out. Results Of the 1 587 cases, 86 cases were NI, and the incidence of NI infection was 5.42%.Among them, the upper respiratory tract infection accounted for 83.87%(78 cases). Univariate conditional Logistic regression analysis indicated that the type of disease, hospitalization days, insight, rehabilitation activities, hand hygiene habits, self-support ability, eating habits, management mode, seasonal and environmental conditions were the risk factors for upper respiratory tract infection in hospitalized children with mental disorders (all P<0.05). Multivariate analysis showed that the odds ratio(OR) of autumn and winter, poor self-support ability, no insight, poor hand hygiene habits, longer hospitalization days (over 14 d), severe mental illness were 19.627 (5.391-23.518), 12.835 (3.436-18.715), 5.427 (1.879-16.921), 3.752 (1.743-16.864), 3.618 (1.659-12.671), 3.361 (1.478-10.527), respectively, which were significantly associated with the occurrence of upper respiratory infection, and the differences were statistically significant (all P<0.05). Conclusions The season, self-support ability, insight, hand hygiene habits, days hospitalization, and disease type are the independent risk factors for upper respiratory infection in hospitalized children with mental disorders, positively controlling and eliminating of independent risk factors for upper respiratory tract may reduce its incidence in the inpationt children. Key words: Mental disorder; Hospitalized child; Nosocomial upper respiratory tract infection; Risk factor; Case-control study

Cannabis and Amphetamine Use and Associated Factors Among School-Going Adolescents in Nine African Countries

ABSTRACTThe aim of this study was to assess the prevalence of cannabis and amphetamine use and associated factors among adolescents in nine African countries. We analyzed cross-sectional data from 25,372 adolescents (mean age 14.3 years, SD = 1.6) from nine African countries that participated in the Global School-Based Student Health Survey (GSHS) in 2009–2013. Information was collected with a self-administered structured questionnaire. Overall, past-month cannabis use was 4.1% and lifetime amphetamine use was 5.1% among students. In multivariable unconditional regression analysis older age, personal attributes (suicidal ideation, current smoking, school truancy, and having had two or more sexual partners), smoking status of the father and/or mother, and environmental stressors (having experienced hunger, been bullied, having been in a physical fight and having been attacked) were associated with both past-month cannabis and lifetime amphetamine use. Measures to prevent and control cannabis and amphetamine use should include personal attributes (suicidal ideation, school truancy, and HIV sexual risk behavior) and environmental stressors (food insecurity and violence).

Risk Factors for Acquiring Scrub Typhus among the Adults.

Background:Behavioral and geographical factors may play a role in the acquisition of scrub typhus infection. In this prospective case–control study, we studied the factors associated with infection.Patients and Methods:Consecutive adult patients admitted with scrub typhus infection over 10 months were recruited. For every case, a geographical control from the same area and a gender-matched clinical control admitted with acute febrile illness were enrolled. The risk factors, which included sanitation, environment, activity, and protective measures, were compared between cases and controls using univariable and multivariable conditional logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI).Results:The study cohort (n = 225; 132 female) aged 44 ± 17 years comprised of 75 cases and 150 controls from mid to low socioeconomic background. When compared with clinical controls, on univariable conditional regression analysis, cases were more likely to be involved in farming or gardening and less likely to have a toilet within the house. On multivariate regression analysis, only involvement in farming or gardening was associated with infection (OR: 4.2, 95% CI: 1.5–11.5). When compared with geographical controls, on univariable conditional regression analysis, cases were less likely to change undergarments or clothes before sleeping (OR: 3.5, 95% CI: 1.3–9.5) and more likely to have rodents in their house (OR: 2.5, 95% CI: 1–6.4) and rest on grass/mud without a mat (OR: 2.4, 95% CI: 1.1–5.3). On multivariate regression analysis, not changing undergarments or clothes tended to be associated with infection (OR: 2.7, 95% CI: 0.98–7.3).Conclusion:Certain behavioral factors predisposed our cohort to develop scrub typhus infection. Lifestyle changes may reduce the burden of scrub typhus in South India.

Maternal and obstetrical predictors of sudden infant death syndrome (SIDS)

Objective: Public Health initiatives, such as the “Safe to Sleep” campaign, have traditionally targeted infants’ risk factors for the prevention of Sudden Infant Death Syndrome (SIDS). However, controversy remains regarding maternal and obstetrical risk factors for SIDS. In our study, we sought out to determine both modifiable and non-modifiable obstetrical and maternal risk factors associated with SIDS.Methods: We conducted a population-based cohort study using the CDC’s Linked Birth–Infant Death data from the United States for the year 2010. The impact of several obstetrical and maternal risk factors on the risk of overall infant mortality and SIDS was estimated using unconditional regression analysis, adjusting for relevant confounders.Results: Our cohort consisted of 4,007,105 deliveries and 24,174 infant deaths during the first year of life, of which 1991 (8.2%) were due to SIDS. Prominent risk factors for SIDS included (OR [95% CI]): black race, 1.89 [1.68–2.13]; maternal smoking, 3.56 [3.18–3.99]; maternal chronic hypertension, 1.73 [1.21–2.48]; gestational hypertension, 1.51 [1.23–1.87]; premature birth <37 weeks, 2.16 [1.82–2.55]; IUGR, 2.46 [2.14–2.82]; and being a twin, 1.81 [1.43–2.29], p < 0.0001. Relative to a cohort of infants who died of other causes, risk factors with a predilection for SIDS were maternal smoking, 2.48 [2.16–2.83] and being a twin, 1.52 [1.21–1.91], p < 0.0001.Conclusions for practice: While certain socio-demographic and gestational characteristics are important risk factors, maternal smoking remains the strongest prenatal modifiable risk factor for SIDS. We recommend the continuation of Public Health initiatives that promote safe infant sleeping practices and smoking cessation during and after pregnancy.

Interleukin-6 polymorphisms and risk of coronary artery diseases in a Chinese population: A case-control study.

Objective:We aimed to evaluate the relationship between IL-6-174G>C, -572G>C and -597G>A polymorphisms and development of coronary artery diseases in a Chinese population.Methods:A total of 275 patients with coronary artery disease and 296 healthy control subjects were collected between January 2013 and November 2014. The IL-6 genotyping for -174G>C, -592G>C and -597G>A polymorphic sites was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) according to the manufacturer instructions.Results:Using unconditional regression analysis, we observed that the AC and CC genotypes of IL-6 -592A>C were associated with the increased risk of developing coronary artery disease when compared with the AA genotype, and the adjusted ORs (95%CI) were 1.63(1.12-2.38) and 2.70(1.57-4.67), respectively. Additionally, the C allele of IL-6 -592A>C (OR=1.65, 95%CI=1.29-2.11) was correlated with a higher risk of developing coronary artery disease in comparison to the A allele. However, no relationship was found between IL-6-174G>C and -597G>A polymorphisms and coronary artery disease susceptibility.Conclusion:This study suggests that IL-6 -592G>C polymorphism is correlated with the risk of coronary artery disease. More well-designed prospective studies based on large sample size, multiple SNPs or haplotypes are required to confirm the current findings.

Genetic polymorphisms in extracellular superoxide dismutase Leu53Leu, Arg213Gly, and Ala40Thr and susceptibility to type 2 diabetes mellitus.

The most common type of endocrine disease is type 2 diabetes mellitus (T2DM); genetic factors contribute to the development to T2DM. In this study, we investigated the role of the Leu53Leu, Arg213Gly, and Ala40Thr polymorphisms in extracellular superoxide dismutase (EC-SOD) gene in the development of T2DM in a Chinese population. DNA was extracted from peripheral blood samples obtained from 256 T2DM patients and 324 control subjects recruited from our hospital between January 2013 and March 2015. DNA was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The obtained data was then statistically analyzed. The chi-square test revealed a statistically significant difference in the genotype frequencies of EC-SOD Ala40Thr (χ2 = 13.26, P = 0.001) between the patients and controls. Unconditional regression analysis indicated that the GA and AA genotypes of EC-SOD Ala40Thr were associated with an increased risk of T2DM compared to the GG genotype {adjusted odds ratio (OR) [95% confidence interval (CI)] = 1.46 (1.01-2.11) and 2.67 (1.48-4.85), respectively}. In the dominant model, the GA+AA genotype of EC-SOD Ala40Thr was correlated with a higher risk of T2DM, in comparison with the GG genotype (OR = 1.64, 95%CI = 1.16-2.33). In the recessive model, AA of EC-SOD Ala40Thr showed a 2.19-fold higher risk of developing T2DM than the GG+GA genotype. In conclusion, people with the Ala40Thr polymorphism in EC-SOD are at a higher risk of developing T2DM; therefore, this may be utilized as a biomarker for early screening of T2DM in a Chinese population.

Association of XRCC1 gene polymorphisms and pancreatic cancer risk in a Chinese population

We conducted a case-control study to assess the role of the XRCC1 Arg399Gln, Arg280His, and Arg194Trp gene polymorphisms in pancreatic cancer susceptibility in a Chinese population. A total of 152 patients diagnosed with pancreatic cancer and 264 control subjects were enrolled in this study between March 2012 and October 2014. XRCC1 Arg399Gln, Arg280His, and Arg194Trp were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. As determined by the chi-squared test, a statistically significant difference was observed between pancreatic cancer patients and control subjects in regard to the genetic distribution of XRCC1 Arg399Gln (χ(2) = 16.13, P < 0.001). Using an unconditional regression analysis, we found that the TT genotype of Arg399Gln was associated with a significantly increased risk of pancreatic cancer (OR = 2.33, 95%CI = 1.20-4.51), and that the CT+TT genotype also significantly increased pancreatic cancer risk (OR = 1.58, 95%CI = 1.04-2.41), compared to the wild-type genotype. In conclusion, we found that XRCC1 Arg399Gln genetic variations are associated with pancreatic cancer development, whereas the XRCC1 Arg280His and Arg194Trp polymorphisms did not affect pancreatic cancer risk.

Matrix metalloproteinase variants associated with risk and clinical outcome of esophageal cancer.

We conducted a case-control study to investigate the role of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 single nucleotide polymorphisms on susceptibility to esophageal squamous cell carcinoma (ESCC) in a Chinese population, and their association with environmental factors. A total of 226 patients with ESCC, and 226 age- and gender-matched healthy controls were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was carried out on MMP2 -1306 C>T (rs243865), MMP3 -1171 5A>6A (rs3025058), and MMP9 -1562 C>T (rs3918242) genotypes. Unconditional regression analysis showed that individuals carrying the MMP2 -1306 TT genotype had a decreased incidence of ESCC compared to those with the CC genotype [odds ratio (OR) = 0.32; 95% confidence interval (CI), 0.10-0.89, P value = 0.02]. Moreover, MMP9 -1562 CC carriers were associated with an increased ESCC risk compared to those with the TT genotype (OR = 2.71; 95%CI, 1.04-7.87, P value = 0.02). In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying the MMP9 -1562 CC genotype had a significantly increased risk of death from ESCC (hazard ratio = 2.97; 95%CI, 1.25-6.87, P value = 0.005). In conclusion, this study showed that the MMP2 -1306 TT and MMP9 -1562 CC genotypes were associated with increased ESCC, and patients carrying the MMP9 -1562 CC genotype had a significantly increased risk of death from ESCC.

Effect of IL-1β, IL-8, and IL-10 polymorphisms on the development of myocardial infarction.

Myocardial infarction (MI) is currently a leading cause of death worldwide, and is caused by various environmental and genetic factors. We therefore conducted a case-control study to investigate the association between polymorphisms in interleukins IL-1β, IL-8, and IL-10 and MI risk. This study recruited 260 MI patients and 285 control subjects. Genotyping of IL-1β +3954C/T, IL-8 -251T/A, IL-10 -1082A/G, and IL-10 -819C/T were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. By comparing the risk factors of MI between the case and control groups, we discovered that MI patients were more likely to have smoking and drinking habits, have a history of hypertension and diabetes, have higher triglycerides and low-density lipoprotein cholesterol levels, and a lower high-density lipoprotein cholesterol level (P < 0.05). Unconditional regression analyses showed that subjects carrying the GG genotype of the IL-10 -1082A/G polymorphism were associated with increased risk of MI, and the OR (95%CI) was 2.04 (1.15-3.65). Our study found that the IL-10 -1082A/G polymorphism plays an important role in influencing the development of MI.

Mobile phone and cordless phone use and the risk for glioma – Analysis of pooled case-control studies in Sweden, 1997–2003 and 2007–2009

We made a pooled analysis of two case-control studies on malignant brain tumours with patients diagnosed during 1997–2003 and 2007–2009. They were aged 20–80 years and 18–75 years, respectively, at the time of diagnosis. Only cases with histopathological verification of the tumour were included. Population-based controls, matched on age and gender, were used. Exposures were assessed by questionnaire. The whole reference group was used in the unconditional regression analysis adjusted for gender, age, year of diagnosis, and socio-economic index. In total, 1498 (89%) cases and 3530 (87%) controls participated. Mobile phone use increased the risk of glioma, OR=1.3, 95% CI=1.1–1.6 overall, increasing to OR=3.0, 95% CI=1.7–5.2 in the >25 year latency group. Use of cordless phones increased the risk to OR=1.4, 95% CI=1.1–1.7, with highest risk in the >15–20 years latency group yielding OR=1.7, 95% CI=1.1–2.5. The OR increased statistically significant both per 100h of cumulative use, and per year of latency for mobile and cordless phone use. Highest ORs overall were found for ipsilateral mobile or cordless phone use, OR=1.8, 95% CI=1.4–2.2 and OR=1.7, 95% CI=1.3–2.1, respectively. The highest risk was found for glioma in the temporal lobe. First use of mobile or cordless phone before the age of 20 gave higher OR for glioma than in later age groups.

Pregnancy outcomes in Marfan syndrome: a retrospective cohort study.

Marfan syndrome (MFS) is a rare connective tissue disease with significant risk for adverse cardiovascular outcomes. Our objective was to evaluate pregnancy and cardiovascular outcomes in pregnant women with MFS. We conducted a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS) database from 2003 to 2010. We used unconditional regression analyses to compare maternal and fetal outcomes among pregnancies in women with and without MFS. Out of the 7,094,400 births in our cohort, 339 deliveries were to women with MFS. There was one maternal death and six aortic dissections among women with MFS. Births to women with MFS were more likely to be premature, odds ratio (OR) 2.15 (1.60-2.89), have intrauterine growth restricted and small for gestational age infants, OR 2.06 (1.24-3.43). Women with MFS were more likely to deliver by cesarean section, OR 1.91 (1.53-2.38) and were at higher risk of major morbidities including cardiac arrhythmias, OR 10.64 (5.49-20.61) and pneumothorax, OR 51.95 (6.18, 437.10). Pregnant women with MFS are at a particularly high risk of adverse pregnancy and cardiovascular events. Preconception counseling should take these risks into consideration and appropriate pregnancy care in tertiary centers should be considered.

Pregnancy Outcomes in Marfan's Syndrome

INTRODUCTION: Marfan's syndrome is a rare connective tissue disease with significant risk for adverse cardiovascular outcomes. Our objective was to evaluate pregnancy and cardiovascular outcomes in pregnant women with Marfan's syndrome. METHODS: We conducted a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database from 2003 to 2010. We used unconditional regression analyses to compare maternal and fetal outcomes among pregnancies in women with Marfan's syndrome with pregnancies without to estimate the adjusted relative risk. RESULTS: Among 7,094,400 births in our cohort, 339 deliveries were to women with Marfan's syndrome. There was one maternal death and six aortic dissections or ruptures among births to women with Marfan's syndrome. Births to women with Marfan's syndrome were more likely to be premature (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.60–2.89) and have intrauterine growth-restricted and small-for-gestational-age neonates (OR 2.06, 95% CI 1.24–3.43). Births among women with Marfan's syndrome were more commonly by cesarean delivery (OR 1.91, 95% CI 1.53–2.38) with an increased risk of forceps deliveries (OR 6.35, 95% CI 4.10–9.83) and vacuum deliveries (OR 2.01, 95% CI 1.36–2.96). Women with Marfan's syndrome were at higher risk of major morbidities including cardiac arrhythmias (OR 10.64, 95% CI 5.49–20.61), venous thromboembolisms (OR 5.24, 95% CI 1.96–14.04), disseminated intravascular coagulation (OR 7.33, 95% CI 1.83–29.38), and pneumothorax (OR 51.95, 95% CI 6.18–437.10). CONCLUSION: Women with Marfan's syndrome are at particularly high risk of adverse pregnancy and cardiovascular events during pregnancy. Preconceptional counseling should take into consideration these risks and appropriate pregnancy care in tertiary centers should be considered.

Multiple myeloma and occupation: A pooled analysis by the International Multiple Myeloma Consortium

Objective: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case–control studies. Methods: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). Results: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR=1.50, 95% CI 0.9–2.3), while other farming jobs did not. Metal processors (OR=1.55, 95% CI 0.9–2.3), female cleaners (OR=1.32, 95% CI 1.0–1.8), and high level exposure to organic solvents (OR=1.38, 95% CI 0.96–1.8) also showed moderately increased risks. Conclusions: Additional case–control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.

Common Variants of the Thyroglobulin Gene Are Associated with Differentiated Thyroid Cancer Risk

Genetic factors are important in thyroid cancer susceptibility. Recently, it has been reported that there are associations of certain chromosome regions with thyroid cancer. In this case-control study, we sought to determine whether there is an association between differentiated thyroid cancer (DTC) and variants in regions of chromosome 8q. We used a case-control association design in a population of 877 individuals (398 patients with sporadic DTC and 479 healthy controls). The iPLEX technology was applied to analyze seven single-nucleotide polymorphisms (SNPs) in chromosome 8q: two SNPs that map at 8q24, previously reported as risk markers in different types of cancer, two SNPs in the thyrotropin-releasing hormone receptor gene (TRHR), and three SNPs in the thyroglobulin gene (TG). Risk assessment was done by unconditional regression analysis. The two SNPs that map at 8q24, rs6983267 and rs1447295, and the two TRHR polymorphisms showed no association with DTC. No association was also found for the exon 33 TG polymorphism. The two TG polymorphisms in the exon 10-12 cluster, however, were associated with an increased risk of DTC (dominant model odds ratio = 1.80, 95% confidence interval = 1.30-2.50, p < 0.001). In this study, we show for the first time that the TG gene is a susceptibility factor for thyroid cancer. Although these conclusions are based on a large population, additional studies are warranted to support these data.

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at‐risk Italian population

We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.

Venous thromboembolism and oral contraceptive use: a methodological study of diagnostic suspicion and referral bias

Background In studies of oral contraceptive oral contraceptive use and risk of venous thromboembolism, bias related to heightened diagnostic suspicion and preferential referral of oral contraceptive users has been an issue. The aim of our study was to determine the presence and potential impact of diagnostic suspicion and referral bias.Methods We conducted a case/non-case study in 21 regional study centers in Germany and, in parallel, a conventional case-control study using the same cases but randomly selected population controls from the same areas. Women with symptoms compatible with venous thromboembolism were included in the study between 1994 and 1999, and classified as cases or non-cases (first reference group) according to the diagnostic work-up (case/non-case study). A second reference group consisted of population controls (conventional case-control study as an internal comparison for the case/non-case study): 606 cases, 462 non-cases and 2942 population controls aged 15–49 years. Adjusted unconditional regression analyses were performed.Results Adjusted odds ratios for venous thromboembolism in oral contraceptive users were systematically higher in the classical case-control study compared to the case/non-case approach (using the same cases) across all subgroup analyses (e.g. for idiopathic cases, the odds ratio was 67% higher in the case-control study: 4.33 (95% confidence interval (CI) 3.27–5.74) versus 2.60 (95% CI 1.75–3.88)). We found a significantly increasing trend of oral contraceptive use in four categories of increasingly sophisticated diagnostic tests that were applied to 1067 women with a suspicion of venous thromboembolism, irrespective of the outcome. Stratified analysis showed the diagnostic level to be a confounder.Conclusion In our population-based study with the possibility of internal comparison, we found clear evidence that diagnostic suspicion and referral bias does play an important role in case-control studies of venous thromboembolism risk among oral contraceptive users. This underlines the importance of making an effort to avoid this bias when designing a new study.