Large Population-based Case Control Research Articles

Abstract 4320: Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension

Abstract Mitochondria are the primary source of cellular energy. Mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) has high genetic heritability and inter-individual variation of mtDNA copy number in PBLs has been associated with the risk of several human cancers. In this study, we investigated into the link between mtDNA and clear-cell renal cell carcinoma (ccRCC) in a large population-based case control study. We measured relative mtDNA copy number in PBLs from 616 Caucasian ccRCC cases and 603 controls frequency-matched on age, gender, and ethnicity. In the analyses of controls only, there was a significant inverse correlation between age and mtDNA copy number (P=0.001); men had significantly lower mtDNA copy number than women (P<0.001); and both smoking and hypertension had a negative effect on mtDNA copy number (P=0.03 and 0.04, respectively). We found a significantly lower mtDNA copy number in cases compared to controls (mean±SD: 1.16±0.37 versus 1.21±0.39, P=0.04). Dichotomized at the median level of mtDNA copy number in controls, individuals with lower mtDNA copy number were at an increased risk of ccRCC (OR=1.20, 95% CI: 0.96-1.51, P=0.11) adjusting for age, gender, smoking status, BMI, and history of hypertension in a multivariate logistic regression analysis. In stratified analyses, the association between lower mtDNA copy number and increased ccRCC risks reached statistical significance in younger aged (age<60) individuals (OR=1.56, 95% CI: 1.12-2.15, P=0.01), women (OR=1.57, 95% CI: 1.06-2.35, P=0.03), and individuals without history of hypertension (OR=1.48, 95% CI: 1.08-2.04, P=0.02). Interestingly, there was a significant interaction between age and mtDNA copy number, and between a history of hypertension and mtDNA copy number in elevating ccRCC risk (P for interaction=0.02 and 0.03, respectively). In summary, our data showed that several established risk factors of ccRCC, including advanced age, male sex, smoking, and history of hypertension, negatively impacted mtDNA copy number in PBLs. Lower mtDNA copy number in PBLs was associated with significantly increased risk of ccRCC in younger aged individuals, women, never smokers, and those without a history of hypertension. There was a significant interaction between age and mtDNA, and a history of hypertension and mtDNA in elevating the risk of ccRCC. These findings indicate that the association between mtDNA copy number in PBLs and ccRCC risk may be modified by various host characteristics (age, gender, smoking, and history of hypertension), providing novel insight into the role of mtDNA in modulating RCC tumorigenesis. Citation Format: Xin Wang, Stephanie Melkonian, Jian Gu, David Chang, Nizar Tannir, Christopher Wood, Xifeng Wu. Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4320. doi:10.1158/1538-7445.AM2014-4320

Genetic polymorphisms of IFNG and IFNGR1 in association with the risk of pulmonary tuberculosis

Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population. This population-based case control study consisted of 1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI). After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76-0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09-1.41). Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.

Helicobacter pylori Seropositivities and Risk of Pancreatic Carcinoma

Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain-specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common. We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays. Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index. Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma. H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site.

Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case–control study

We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children. Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age, duration of diabetes and HbA1c at the time of pump start. HbA1c, anthropometric data, episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospectively. A total of 345 patients on pump therapy were matched to controls on injections. The mean age, duration of diabetes at pump start and length of follow-up were 11.4 (± 3.5), 4.1 (± 3.0) and 3.5 (± 2.5) years, respectively. The mean HbA1c reduction in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA1c remained significant throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years (p < 0.001). In contrast, severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower in the pump cohort (2.3 vs 4.7 per 100 patient-years, p = 0.003) over the 1,160 patient-years of follow-up. This is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control, and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections.

Dental diagnostic X-ray exposure and risk of benign and malignant brain tumors

BackgroundThis study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case–control study. Materials and methodsWe identified 4123 BBT cases and 16 492 controls without BBT (study 1) and 197 MBT cases and 788 controls without MBT (study 2) from Taiwan National Health Insurance claim data. The risks of both types of tumor were estimated in association with the frequency of received dental diagnostic X-ray. ResultsThe mean ages were ∼44.2 years in study 1 and 40.6 years in study 2. Multivariable unconditional logistic regression analysis showed that the risk of BBT increases as the frequency of received dental diagnostic X-ray increases. The BBT odds ratio increased from 1.33 [95% confidence interval (CI) 1.22–1.44] for those with annual mean X-ray examination of less than one to 1.65 (95% CI 1.37–1.98) for those with three or more X-ray examinations, after controlling for comorbidities. No significant association was found between MBTs and dental diagnostic X-ray exposure. ConclusionsExposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.

Clinical aspects and self-reported symptoms of sequelae of Yersinia enterocolitica infections in a population-based study, Germany 2009-2010.

BackgroundFoodborne Yersinia enterocolitica infections continue to be a public health problem in many countries. Consumption of raw or undercooked pork is the main risk factor for yersiniosis in Germany. Small children are most frequently affected by yersiniosis. In older children and young adults, symptoms of disease may resemble those of appendicitis and may lead to hospitalization and potentially unnecessary appendectomies. Y. enterocolitica infections may also cause sequelae such as reactive arthritis (ReA), erythema nodosum (EN), and conjunctivitis.MethodsWe studied clinical aspects of yersiniosis, antimicrobial use, and self-reported occurrence of appendectomies, reactive arthritis, erythema nodosum and conjunctivitis. To assess post-infectious sequelae participants of a large population-based case–control study on laboratory-confirmed Y. enterocolitica infections conducted in Germany in 2009–2010 were followed for 4 weeks.ResultsDiarrhea occurred most frequently in children ≤4 years (95%); abdominal pain in the lower right quadrant was most common in children 5–14 years of age (63%). Twenty-seven per cent of patients were hospitalized, 37% were treated with antimicrobials. In 6% of yersiniosis patients ≥5 years of age, appendectomies were performed. Self-reported symptoms consistent with ReA were reported by 12% of yersiniosis patients compared to 5% in a reference group not exposed to yersiniosis. Symptoms consistent with EN were reported by 3% of yersiniosis patients compared to 0.1% in the reference group. Symptoms of conjunctivitis occurred with the same frequency in yersiniosis patients and the reference group.ConclusionsAcute Y. enterocolitica infections cause considerable burden of illness with symptoms lasting for about 10 days and hospitalizations in more than a quarter of patients. The proportion of yersiniosis patients treated with antimicrobial drugs appears to be relatively high despite guidelines recommending their use only in severe cases. Appendectomies and post-infectious complications (ReA and EN) are more frequently reported in yersiniosis patients than in the reference group suggesting that they can be attributed to infections with Y. enterocolitica. Physicians should keep recent Y. enterocolitica infection in mind in patients with symptoms resembling appendicitis as well as in patients with symptoms of unclear arthritis.

Body mass index, body mass change, and risk of oral cavity cancer: results of a large population-based case–control study, the ICARE study

The association between body mass index (BMI) and the risk of oral cavity cancer, suggested by the few available studies, is controversial because of weight loss preceding cancer diagnosis and possible confounding by tobacco and alcohol consumption. The aim of this study was to evaluate in France, a high-incidence country, the association between the risk of oral cavity cancer and body mass index at interview, 2 years before the interview and at age 30, as well as BMI change. We used data from a population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study, with personal interviews and standardized questionnaires including 689 cases of oral cavity squamous cell carcinoma and 3,481 controls. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression and were adjusted for gender, age, area of residence, education, tobacco smoking, and alcohol drinking. ORs were increased in underweight subjects at interview (OR 6.25, 95% CI 3.74-10.45). No association with underweight 2 years before the interview and at age 30 was found. Overweight and obesity at interview, 2 years before the interview and at age 30 were associated with decreased ORs (ranging from 0.13 to 0.60). BMI gain greater than 5% between age 30 and 2 years before the interview was inversely associated with oral cavity cancer (OR 0.42, 95% CI 0.33-0.54). These associations were stronger in men, and in smokers and drinkers. These results add further support to the existence of a reduced risk of oral cavity cancer among overweight and obese people or among people who increased their BMI in adulthood. The underlying mechanisms remain to be clarified.

Risk of adult acute and chronic myeloid leukemia with cigarette smoking and cessation

BackgroundCigarette smoking is an established risk factor for adult myeloid leukemia, particularly acute myeloid leukemia (AML), but less is known about the nature of this association and effects of smoking cessation on risk. MethodsIn a large population-based case–control study of myeloid leukemia that included 414 AML and 185 chronic myeloid leukemia (CML) cases and 692 controls ages 20–79 years, we evaluated risk associated with cigarette smoking and smoking cessation using unconditional logistic regression methods and cubic spline modeling. ResultsAML and CML risk increased with increasing cigarette smoking intensity in men and women. A monotonic decrease in AML risk was observed with increasing time since quitting, whereas for CML, the risk reduction was more gradual. For both AML and CML, among long-term quitters (≥30 years), risk was comparable to non-smokers. ConclusionsOur study confirms the increased risk of myeloid leukemia with cigarette smoking and provides encouraging evidence of risk attenuation following cessation.

Chronic heart failure and risk of hospitalization with pneumonia: A population-based study

BackgroundChronic heart failure may increase risk of pneumonia due to alveoli flooding and reduced microbial clearance. We examined whether chronic heart failure is a risk factor for pneumonia-related hospitalization. MethodsIn this large population-based case–control study we identified adult patients with a first-time primary or secondary discharge diagnosis of viral or bacterial pneumonia between 1994 and 2008, using health care databases in Northern Denmark. For each case, ten sex- and age-matched population controls were selected from Denmark's Civil Registration System. We used conditional logistic regression to compute relative risk (RR) for pneumonia-related hospitalization among persons with and without pre-existing heart failure, overall and stratified by medical treatment. We controlled for a wide range of comorbidities, socioeconomic markers and immunosuppressive treatment. ResultsThe study included 67,162 patients with a pneumonia-related hospitalization and 671,620 population controls. The adjusted OR for pneumonia-related hospitalization among persons with previous heart failure was 1.81 (95% confidence interval (CI): 1.76–1.86) compared with other individuals. The adjusted pneumonia RR was lower for heart failure patients treated with thiazides only (adjusted OR=1.56, 95% CI: 1.46–1.67), as compared with patients whose treatment included loop-diuretics and digoxin as a marker of increased severity (adjusted OR=1.95, 95% CI: 1.85–2.06) or both loop-diuretics and spironolactone (adjusted OR=2.02, 95% CI: 1.90–2.15). The population-attributable risk of pneumonia hospitalizations caused by heart failure in our population was 6.2%. ConclusionsPatients with chronic heart failure, in particular those using loop diuretics, have markedly increased risk of hospitalization with pneumonia.

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

BackgroundGenetic variation at 1p13 modulates serum lipid levels and the risk of coronary heart disease through the regulation of serum lipid levels. Here we investigate if the interaction between genetic variants at 1p13 and serum lipid levels affects the risk of non-fatal myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP), a large population based case control study.MethodsIn the present study only non fatal MI cases (n = 1213, men/women: 852/361) and controls (n = 1516, men/women =1054/507) matched by age, sex and residential area, were included. Three SNPs 12740374 G/T, rs599839A/G and rs646776T/C mapping at 1p13 were analysed for association with serum lipid levels and the risk of MI by a weighted least square regression and logistic regression analyses, respectively. To analyse the effect of the interaction between genetic variants and serum lipid levels on the risk of MI, we applied the biological model of interaction that estimates the difference in risk, expressed as OR (95%CI), observed in the presence and in the absence of both exposures. One derived measure is the Synergy index (S) and 95%CI, where S > 1 indicates synergy and S < 1 antagonism between the two interaction terms.ResultsRs12740374G/T and rs646776T/C were in strong linkage disequilibrium (LD) (r2 = 0.99), therefore only rs599839A/G and rs646776 were included in the analysis. Consistently with published data, presence of the rare genotypes was associated with reduced total-, LDL-cholesterol and ApoB serum levels (all p < 0.05) as compared to the reference genotype, but was not associated with the risk of MI.However, the increased risk of MI observed in individual exposed to high (≥75th percentile) serum lipid levels was offset in subjects carrying the rare alleles G and C. In particular, the risk of MI associated with high ApoB serum levels OR (95%CI) 2.27 (1.86-2.77) was reduced to 1.76 (1.33-2.34) in the presence of the G allele at rs599839 with an S of 0.47 (0.20-0.90).ConclusionsThese results indicate that an antagonism between ApoB serum levels and genetic variants at 1p13 contributes to reduce the risk of non-fatal MI in the presence of high ApoB serum levels.

Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area

Obesity has been consistently associated with increased risk of pancreatic cancer incidence and mortality. However, studies of obesity and overall survival in patients with pancreatic cancer are notably lacking, especially in population-based studies. Active and passive follow-up were used to determine vital status and survival for 510 pancreatic cancer patients diagnosed from 1995 to 1999 in a large population-based case-control study in the San Francisco Bay Area. Survival rates were computed using Kaplan-Meier methods. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated in multivariable Cox proportional hazards models as measures of the association between pre-diagnostic obesity and pancreatic cancer survival. An elevated hazard ratio of 1.3 (95 % CI, 0.91-1.81) was observed for obese [body mass index (BMI) ≥ 30] compared with normal range BMI (<25) patients. Associations between BMI and overall survival did not statistically significantly vary by known prognostic and risk factors (all p-interaction ≥0.18), yet elevated HRs consistently were observed for obese compared with normal BMI patients [localized disease at diagnosis (HR, 3.1), surgical resection (HR, 1.6), ever smokers (HR, 1.6), diabetics (HR, 3.3)]. Poor survival was observed among men, older patients, more recent and current smokers, whereas improved survival was observed for Asian/Pacific Islanders. Our results in general provide limited support for an association between pre-diagnostic obesity and decreased survival in patients with pancreatic cancer. Patterns of reduced survival associated with obesity in some patient subgroups could be due to chance and require assessment in larger pooled studies.

Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large population-based case–control study in Mexican women

Epidemiologic studies have suggested that higher levels of circulating vitamin D may reduce breast cancer risk, but no studies have investigated this association among women in developing countries, and very few studies have further investigated this association according to menopausal status. A population-based case-control study in Mexico with 1,000 incident breast cancer cases aged 35-69 years, enrolled shortly after diagnosis (0-6 days) and frequency-matched to 1,074 controls on age, region, and health care system, was used to assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels with overall, pre- and postmenopausal breast cancer risk. 25(OH)D concentration was measured on a random sub-sample of women (573 cases and 639 matched controls) using a liquid chromatography/tandem mass spectrometry method. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated from multivariable conditional logistic regression models. Serum 25(OH)D concentration (per 10 ng/mL increase) showed a strong inverse association with risk of breast cancer among all (p(trend) = 0.001), pre- (p(trend) = 0.006) and postmenopausal women (p(trend) = 0.0001). Compared with a predefined lower concentration of 25(OH)D (<20 ng/mL), higher levels (>30 ng/mL) were associated with lower overall (OR = 0.53, 95 % CI: 0.28-1.00; p(trend) = 0.002), pre- (OR = 0.60, 95 % CI: 0.16-2.17; p(trend) = 0.07) and postmenopausal (OR = 0.37, 95 % CI: 0.16-0.82; p(trend) = 0.004) breast cancer risk. The results of this large population-based case-control study indicate an inverse association between circulating vitamin D levels and breast cancer risk among pre- and postmenopausal Mexican women.

Free and Total Protein S Antigen Levels on the Risk of Venous Thrombosis: Results From the MEGA Study

Abstract 538 Context:Conflicting data have been reported on the risk for venous thrombosis in individuals with low total protein S levels (i.e. type I protein S deficiency) and low free protein S levels with normal total protein S levels (i.e. type III protein S deficiency). This may be due to small numbers, wrong cut off level or inclusion of individuals with mild transitory decrements in protein S levels. Most studies that showed that type I and type III protein S deficiency were related with an increased risk for venous thrombosis, have been performed in thrombophilic families, suggesting that these deficiencies are inherited. As the prevalence of inherited type I or type III protein S deficiency is not known, the relevance of these findings within normal populations remain to be established. Objectives:To assess the risk of first venous thrombosis in persons with low levels of free protein S or total protein S in a large population-based case–control study. Design:MEGA study, 4956 consecutive patients aged 18 to 70 years with a first episode of venous thrombosis were included. Age- and sex-matched controls were partners of patients (n=3297) or individuals recruited by random digit dialing (n=3000). DNA was obtained by standard methods and was available for 4485 patients and 4889 control subjects. Citrated plasma was available for 2471 patients and 2940 controls. Molecular basis for protein S deficiency was investigated by analysis of copy number variation of PROS1 and sequencing of individuals with the lowest levels of protein S in attempt to explain the different findings in risk estimates between families and population studies. Statistical analysis:Odds ratios were adjusted for age and sex (matching factors) for levels of free/total protein S and their 95% confidence levels (95% CIs) with the use of logistic regression. The 2.5th-97.5th percentile of both total and free protein S in control subjects that did not use vitamin K antagonists (VKA) at time of blood draw were considered as the reference range. Individuals that used VKA at time of blood draw were excluded when calculating relative risk estimates. Furthermore, a preplanned sensitivity analysis was performed where we excluded estrogen users and pregnant women at time of blood draw. Results:Individuals with low free protein S levels or low total protein S levels (<2.5th percentile) were not at increased risk of venous thrombosis as compared to individuals with protein S levels in the 2.5th-97.5th percentile; odds ratio 0.82 (95% CI, 0.56–1.21) and 0.90 (95% CI, 0.62–1.31) respectively. Excluding all women who used estrogens or were pregnant/puerperic at time of venous thrombosis or at time of blood sampling increased the odds ratios slightly to 1.55 (95% CI, 0.84–2.88) for individuals with low free protein S levels and to 1.28 (95% CI, 0.70–2.35) in individuals with low total protein S levels. We subsequently compared decreasing cut off values of free and total protein S levels on the risk of venous thrombosis as compared to the same reference group. Although numbers became small, it appeared that a free protein S cut off level of < 0.20th or < 0.10th percentile could identify individuals at high risk of venous thrombosis (odds ratios 2.01; 95% CI, 0.57–7.15, and 5.44; 95% CI, 0.61–48.78, respectively). Even extremely low (<0.10th percentile) total protein S levels were not associated with venous thrombosis. Only one patient had a copy number variation of PROS1 in 2270 consecutive samples tested. Currently, we are sequencing the PROS1 gene in all individuals with protein S levels <1st percentile of which results will be available before the ASH conference of 2011. Conclusion:Low free protein S and low total protein S levels could not identify individuals at risk for venous thrombosis in a population based study. Although extremely low free protein S levels were associated with an increased risk for venous thrombosis, numbers were too small to support testing on free protein S in an unselected group of venous thrombosis patients. Disclosures:No relevant conflicts of interest to declare.

Periconceptional febrile illnesses and congenital heart defects

Through a large population-based case control study, Oster et al add precision to the evidence of effects of maternal illness on the likelihood of congenital heart defects (CHD) in offspring. The specificity of the events considered (ie, “fever of 101°F or higher” or “influenza [flu]” in the periconceptional period from 3 months prior to conception until 3 months of gestation) and outcomes found (ie, statistically significantly increased odds ratio for right-sided obstructive lesions, as well as atrioventricular septal defects in cases with Down syndrome, but no association with CHD in aggregate) are impressive. Investigators also found that use of antipyretics tended to decrease these associations. An important limitation of the study is that the specific antipyretic agents used were not analyzed. Effects of use of antipyretics in pregnancy are controversial; some studies suggest increased odds of congenital defects with exposure to certain agents. It is noteworthy that the time period of this study preceded widespread use of non-steroidal anti-inflammatory agents. The authors provide an excellent review of previous studies that sought relationship of maternal illnesses with CHD, with discussion of their study methodology and findings in context. There is food for thought regarding pathophysiology, further impetus for implementation of universal annual influenza vaccination policy, and reason to consider treating febrile illness in the periconceptional period with antipyretic therapy, such as acetaminophen. Article page 990▶ Associations Between Maternal Fever and Influenza and Congenital Heart DefectsThe Journal of PediatricsVol. 158Issue 6PreviewTo examine associations between maternal reports of prenatal fever or influenza and congenital heart defects (CHDs), and to evaluate whether those associations varied with antipyretic use. Full-Text PDF

Correlation Between Obesity and High Density Lipoprotein Cholesterol (HDL-C) in Breast Cancer Patients of Southern Rajasthan

Despite advances in management of breast cancer, etiology is still elusive. Diet, obesity and other life style factors have been implicated in its etiology. We assessed the role of obesity and HDL-C levels in patients with rural background in etiology of breast cancer. To know the relation between obesity and incidence of breast cancer in local population. Also to know serum HDL-C level in breast cancer and its correlation with breast cancer. A nested pilot study of 50 breast cancer patients was done and matched with 50 healthy women as controls. Obesity was measured by weight, height, BMI (Body Mass Index), waist circumference (WC), Hip Circumference (HC), WC/HC ratio, and Serum High Density Lipoprotein Cholesterol (HDL-C) was measured in patients and in controls. There was no significant difference in distribution of weight (p = 0.298), height (p = 0.653), BMI (p = 0.459) and WHR (p = 0.052) among cases and controls. HDL-C level was observed to be significantly lower in cases than control group (p = 0.017).Breast cancer patients of pre menopausal age had significantly low Weight (p = 0.037) and BMI (p = 0.011) than post menopausal patients. In our study population only low HDL-C level had significant correlation with breast cancer and none of the other anthropometric measurements were associated with breast cancer. However, large population based case control and cohort studies are needed to identify low serum HDL-C as an independent predictor of increased risk of breast cancer.

Abstract 2744: SNP-SNP interaction between a microRNA and its target gene increases risk of non-melanoma skin cancer

Abstract Functional genetic variation in microRNA's has the potential to broadly impact disease processes given the large number of gene targets per microRNA. To date, there are only a few examples of functionally verified mirSNPs; among them is rs2910164 contained in the pre-mir-146a. mir-146a is an important modulator of immune responses, and therefore is of interest for non-melanoma skin cancer (NMSC), a highly antigenic cancer. Using a large population-based case control study of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in New Hampshire, we investigated the impact of this mirSNP on cancer risk, and potential interaction with one of its gene targets (RNASEL, rs486907). While there was no observed risk associated with the C allele of the mir-146a SNP (ORBCC = 0.91, 95% CI 0.74 – 1.10), ORSCC=1.06, 95% CI 0.86 – 1.30), there was a significant interaction between sunburn history and the mirSNP for BCC (pinteraction=0.002). In addition, there was strong interaction between the mir-146a SNP and genetic variation in its target gene RNASEL (BCC, pinteraction=0.01, SCC pinteraction=0.003). Importantly, our study is among the first to demonstrate snp-snp interaction in a microRNA and its target gene. Further, these data imply that RNASEL, an enzyme involved in cellular and viral RNA turnover, is controlled by this miRNA and that this process is important in skin cancer etiology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2744. doi:10.1158/1538-7445.AM2011-2744

IκBα polymorphisms were associated with increased risk of gastric cancer in a southern Chinese population: A case–control study

Aim Nuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case–control study among southern Chinese. Main methods A population-based case–control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2 kb promoter region to the 3.5 kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay. Key findings rs17103265 deletion homozygote (−/−) had significantly increased gastric cancer risk (OR = 2.11, 95% CI = 1.17–3.83, P = 0.01), compared with rs17103265 T homozygote (TT). rs17103265 (−/−) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR = 2.21, 95% CI = 1.19–4.08, P = 0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (−/−) was associated with poorly differentiated gastric cancer (OR = 2.05, 95% CI = 1.07–3.94, P = 0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele ( P < 0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients. Significance IκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population.

Effect of aspirin and NSAIDs on risk and survival from colorectal cancer

BackgroundPrevious studies have shown that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) lower colorectal cancer (CRC) risk. However, the lowest effective NSAID dose, treatment duration, and effects on survival are...

Exposures in painting-related occupations and risk of lung cancer among men: results from two case–control studies in Montreal

BackgroundEvidence that painters may be at risk for lung cancer comes mainly from analyses on job titles rather than on specific exposures found in the environments of painters.MethodsIn the context...

Experience with multiple control groups in a large population-based case–control study on genetic and environmental risk factors

We discuss the analytic and practical considerations in a large case–control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.