Birth weight and other perinatal factors and childhood CNS tumors: A case–control study in California

AimsWe conducted a large registry-based study in California to investigate the association of perinatal factors and childhood CNS tumors, with analysis by tumor subtype.MethodsWe linked California cancer and birth registries to obtain information on 3308 cases and 3308 controls matched on age and sex. We examined the association of birth weight, gestational age, birth order, parental ages, maternal conditions during pregnancy, newborn abnormalities and the risk of childhood CNS tumors using conditional logistic regression, with adjustment for potential confounders.ResultsThe odds ratio (OR) per 1000 g increase in birth weight was 1.11 (95% CI: 0.99–1.24) for total childhood CNS tumors, 1.17 (95% CI: 0.97–1.42) for astrocytoma and 1.28 (95% CI: 0.90–1.83) for medulloblastoma. Compared to average-for-gestational age, large-for-gestational age infants were at increased risk of glioma (OR = 1.86, 95% CI: 0.99–3.48), while small-for-gestational age infants were at increased risk of ependimoma (OR = 2.64, 95% CI: 1.10–6.30). Increased risk of childhood CNS tumors was observed for 5-year increase in maternal and paternal ages (OR = 1.06, 95% CI: 1.00–1.12 and 1.05, 95% CI: 1.00–1.10 respectively). Increased risk of astrocytoma was detected for 5-year increase in paternal age (OR = 1.08; 95% CI: 1.00–1.16) and increased risk of glioma for maternal age ≥ 35 years old (OR = 1.87; 95% CI: 1.00–3.52). Maternal genital herpes during pregnancy was associated with a pronounced increase in risk of total CNS tumors (OR = 2.74; 95% CI: 1.16–6.51). Other (non-sexually transmitted) infections during pregnancy were associated with decreased risk of total CNS tumors (OR = 0.28, 95% CI: 0.09–0.85). Maternal blood/immune disorders during pregnancy were linked to increased risk of CNS tumors (OR = 2.28, 95% CI: 1.08–4.83) and medulloblastoma (OR = 7.13, 95% CI: 0.82–61.03). Newborn CNS abnormalities were also associated with high risk of childhood CNS tumors (OR = 4.08, 95% CI: 1.13–14.76).ConclusionsOur results suggest that maternal genital herpes, blood and immunological disorders during pregnancy and newborn CNS abnormalities were associated with increased risk of CNS tumors. Maternal infections during pregnancy were associated with decreased risk of CNS tumors. Advanced maternal and paternal ages may be associated with a slightly increased risk of CNS tumors. Factors associated with CNS tumor subtypes varied by subtype, an indicator of different etiology for different subtypes.     

Birth weight and other perinatal characteristics and childhood leukemia in California

Aims. We conducted a large registry-based study in California to investigate the association of perinatal factors and childhood leukemia with analysis of two major subtypes, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Methods. We linked California cancer and birth registries to obtain information on 5788 cases and 5788 controls matched on age and sex (1:1). We examined the association of birth weight, gestational age, birth and pregnancy order, parental ages, and specific conditions during pregnancy and risk of total leukemia, ALL and AML using conditional logistic regression, with adjustment for potential confounders. Results. The odds ratio (OR) per 1000 g increase in birth weight was 1.11 for both total leukemia and ALL. The OR were highest for babies weighing ≥4500 g with reference <2500 g: 1.59 (95% CI: 1.05–2.40) and 1.70 (95% CI: 1.08–2.68) for total leukemia and ALL, respectively. For AML, increase in risk was also observed but the estimate was imprecise due to small numbers. Compared to average-for-gestational age (AGA), large-for-gestational age (LGA) babies were at slightly increased risk of total childhood leukemia (OR = 1.10) and both ALL and AML (OR = 1.07 and OR = 1.13, respectively) but estimates were imprecise. Being small-for-gestational age (SGA) was associated with reduced risk of childhood leukemia (OR = 0.81, 95% CI: 0.67–0.97) and ALL (OR = 0.77, 95% CI: 0.63–0.94), but not AML. Being first-born was associated with decreased risk of AML only (OR = 0.70; 95% CI: 0.53–0.93). Compared to children with paternal age <25 years, children with paternal age between 35 and 45 years were at increased risk of total childhood leukemia (OR = 1.12; 95% CI: 1.04–1.40) and ALL (OR = 1.23; 95% CI: 1.04–1.47). None of conditions during pregnancy examined or maternal age were associated with increased risk of childhood leukemia or its subtypes. Conclusions. Our results suggest that high birth weight and LGA were associated with increased risk and SGA with decreased risk of total childhood leukemia and ALL, being first-born was associated with decreased risk of AML, and advanced paternal age was associated with increased risk of ALL. These findings suggest that associations of childhood leukemia and perinatal factors depend highly on subtype of leukemia.     

Maternal pregnancy events and exposures and risk of hepatoblastoma: A Children's Oncology Group (COG) study

Background: Hepatoblastoma is a rare childhood liver cancer with an obscure etiology, however it is potentially associated with selected pregnancy events and hepatoblastoma risk in offspring. Methods: Adjusted unconditional logistic regression estimated odds ratios (OR) and corresponding 95% confidence intervals (CI) for self-reported pregnancy events and medication use in a sample of mothers of 383 childhood hepatoblastoma cases and 387 controls. Results: Risk of hepatoblastoma was significantly associated with maternal first trimester weight gain (OR = 1.02; 95% CI 1.00, 1.04 per 1 lb increase and nearly significantly with maternal multivitamin use (OR = 0.73; 95% CI 0.51, 1.03). Hepatoblastoma was not associated with other maternal weight changes, maternal illness or medication use during pregnancy. Conclusion: We found little evidence that maternal illness or most medication use during pregnancy are associated with hepatoblastoma in offspring.     

Risk of malignant childhood germ cell tumors in relation to demographic,gestational, and perinatal characteristics

BackgroundChildhood germ cell tumors (GCTs) are a rare assortment of neoplasms, with mostly unknown etiology, that are believed to originate very early in life. Few studies have examined risk factors by histologic subtype, despite evidence of different risk profiles.Materials and methodsIn this population-based case-control study, 451 childhood malignant GCT cases ages 0–5 years were identified from the California Cancer Registry. Differentiating between common histologic subtypes, we identified 181 yolk sac tumors, 216 teratomas, and 54 rarer subtypes. Cases were linked to their birth certificates and 271,381 controls, frequency matched by birth year, were randomly selected from California birthrolls to investigate the contributions of demographic, gestational, and pregnancy factors using unconditional logistic regression analysis.ResultsCompared to non-Hispanic whites, Asian/Pacific Islander children were at an increased risk for developing GCTs (odds ratio [OR] = 1.94; 95% confidence interval [CI] = 1.47, 2.56). Among pregnancy complications and procedures, yolk sac tumors were positively associated with the presence of fetopelvic disproportion (OR = 2.97; 95% CI = 1.55, 5.68), while teratomas were strongly associated with polyhydramnios or oligohydramnios (OR = 14.76; 95% CI = 7.21, 30.19) and the presence of an ear, face, or neck anomaly at birth (OR = 93.70; 95% CI = 42.14, 208.82).ConclusionsMalignant yolk sac tumors and malignant teratomas exhibited distinct demographic and gestational characteristics; additionally, complications in pregnancy and labor may be brought on by specific histologic subtypes.     

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.     

Occupation and risk of prostate cancer in Canadian men: A case-control study across eight Canadian provinces

BackgroundThe etiology of prostate cancer continues to be poorly understood, including the role of occupation. Past Canadian studies have not been able to thoroughly examine prostate cancer by occupation with detailed information on individual level factors.MethodsOccupation, industry and prostate cancer were examined using data from the National Enhanced Cancer Surveillance System, a large population-based case-control study conducted across eight Canadian provinces from 1994 to 1997. This analysis included 1737 incident cases and 1803 controls aged 50 to 79 years. Lifetime occupational histories were used to group individuals by occupation and industry employment. Odds ratios and 95% confidence intervals were calculated and adjustments were made for known and possible risk factors.ResultsBy occupation, elevated risks were observed in farming and farm management (OR = 1.37, 95% CI 1.02–1.84), armed forces (OR = 1.33, 95% CI 1.06-1.65) and legal work (OR = 2.58, 95% CI 1.05–6.35). Elevated risks were also observed in office work (OR = 1.20, 95% CI 1.00–1.43) and plumbing (OR = 1.77, 95% CI 1.07–2.93) and with ≥10 years duration of employment. Decreased risks were observed in senior management (OR = 0.65, 95% CI 0.46–0.91), construction management (OR = 0.69, 95% CI 0.50–0.94) and travel work (OR = 0.37, 95% CI 0.16–0.88). Industry results were similar to occupation results, except for an elevated risk in forestry/logging (OR = 1.54, 95% CI 1.06–2.25) and a decreased risk in primary metal products (OR = 0.70, 95% CI 0.51–0.96).ConclusionThis study presents associations between occupation, industry and prostate cancer, while accounting for individual level factors. Further research is needed on potential job-specific exposures and screening behaviours.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

Ascaris lumbricoides and Trichuris trichiura infections associated with wastewater and human excreta use in agriculture in Vietnam

BackgroundWe assessed the risk of helminth infections in association with the use of wastewater and excreta in agriculture in Hanam province, northern Vietnam. In two cross-sectional surveys, we obtained samples from 1,425 individuals from 453 randomly selected households. Kato-Katz thick smear and formalin-ether concentration techniques were used for helminth diagnosis in two stool samples per person. Socio-demographic and water, sanitation and hygiene related characteristics, including exposure to human and animal excreta and household wastewater management, were assessed with a questionnaire.ResultsOverall 47% of study participants were infected with any helminth (Ascaris lumbricoides 24%, Trichuris trichiura 40% and hookworm 2%). Infections with intestinal protozoa were rare (i.e. Entamoeba histolytica 6%, Entamoeba coli 2%, Giardia lamblia 2%, Cryptosporidium parvum 5% and Cyclospora cayetanensis 1%). People having close contact with polluted Nhue River water had a higher risk of helminth infections (odds ratio [OR] = 1.5, 95% confidence interval [CI] 1.1–2.2) and A. lumbricoides (OR = 2.1, 95% CI 1.4–3.2), compared with those without contact. The use of human excreta for application in the field had an increased risk for a T. trichiura infection (OR = 1.5, 95% CI 1.0–2.3). In contrast, tap water use in households was a protective factor against any helminth infection (i.e. T. trichiura OR = 0.6, 95% CI 0.4–0.9). Prevalences increased with age and males had generally lower prevalences (OR = 0.8, 95% CI 0.6–1.0), participants performing agricultural (OR = 1.5, 95% CI 1.1–2.1) and having a low educational level (OR = 1.7, 95% CI 1.2–2.4) were significantly associated with helminth infections. None of the factors related to household's sanitary condition, type of latrine, household's SES, use of animal excreta, and personal hygiene practices were statistically significant associated with helminth infection.ConclusionsOur study suggests that in agricultural settings, direct contact with water from Nhue River and the use of human excreta as fertiliser in the fields are important risk factors for helminth infection. Daily use of clean water is likely to reduce the risk of worm infection. Deworming policies and national programs should give more attention to these agricultural at risk populations.     

Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: A population-based assessment

PurposeData from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case–control studies.MethodsWiring codes were calculated for participating cases, n = 310; and non-participating cases, n = 66; as well as for three control groups: first-choice participating, n = 174; first-choice non-participating, n = 252; and replacement (non-first choice participating controls), n = 220.ResultsParticipating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR = 1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR = 1.06, 95% CI: 0.71, 1.60).ConclusionsThe observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS.     

Impact of HLA-class I alleles on response to HCV treatment in a cohort of Egyptian patients

Extensive allele diversity is observed in HLA associations with response to HCV combined therapy (pegylated interferon + ribavitin) in different global ethnic populations. The aim of the study is to assess the frequency and association of certain HLA-class I alleles in Egyptian persons with persistent HCV and others with sustained viral response (SVR).Material and methodsThe study was a retrospective cohort study that included 246 HCV patients who received combined therapy; 106 cases responded to treatment (SVR) and 140 individuals did not respond to treatment (persistent HCV infection). Both groups are subjected to genotyping for HLA-class I.ResultsAccording to logistic regression analysis, Cw17 was considered as the most predictor allele as it was the highest significant allele (OR = 16.70; 95% CI: 2.64–105.58; P = 0.003), whereas the presence of the HLA-B45 and HLA-B27 alleles has a 19.35-fold risk and 15.7 fold risk, respectively of non-response to interferon therapy in chronic HCV patients (OR = 19.35; 95% CI: 1.05–357.24; P = 0.04) and (OR = 15.69; 95% CI: 1.179–208.9; P = 0.04) can act also as high predictor alleles, and the lowest significant predictor allele was B44 (OR = 6.535; 95% CI: 1.55–27.63; P = 0.01). The presence of the HLA-A alleles might have a limited role in prediction for the non-responders, as the A32 was significantly higher among the SVR patients, but, it cannot have a predictor role (OR: 0.161, CI: 0.03–1.056, P = 0.049).ConclusionCw17, HLA-B45, and HLA-B27 alleles can predict the nonresponders to HCV combined therapy.     

Genetic polymorphism of epidermal growth factor 61A>G and cancer risk: A meta-analysis

Background: Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but the results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of association between this polymorphism and risk of cancer. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies. Case-control studies containing available genotype frequencies of EGF 61A>G were chose, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Results: 23 case-control studies including 5578 cases and 7306 controls were identified. This meta-analysis showed significant effect of EGF 61A>G on cancer risk (GG vs. AA: OR = 1.34, 95%CI = 1.05–1.72; GG vs. GA + AA: OR = 1.23, 95%CI = 1.03–1.47; GG + GA vs. AA: OR = 1.18, 95%CI = 1.02–1.38). In subgroup analysis, significant increased risk was found in gastric cancer and glioma in additive model (OR = 1.54, 95%CI = 1.13–2.12; OR = 1.69, 95%CI = 1.21–2.37) and in recessive model (OR = 1.29, 95%CI = 1.10–1.52; OR = 1.54, 95%CI = 1.16–2.04). Conclusion: This meta-analysis suggested that the EGF 61G allele is a risk factor of cancer, especially for gastric cancer and glioma.     

Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population

BackgroundTo explore the association between hypomethylation of repetitive elements (LINE-1, Sat2, and ALU) in blood leukocyte DNA and risks of gastric lesions, and development of gastric cancer (GC), a population-based study was conducted in a high-risk area of GC in China.MaterialsMethylation levels were determined by MethyLight in 902 subjects with various gastric lesions from two cohort studies at baseline and 276 subjects with long-term follow-up data.ResultsThe frequency of LINE-1 or Sat2 hypomethylation was significantly increased in subjects with dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. The odds ratios (ORs) were 2.22 [95% confidence interval (CI): 1.45–3.40] for LINE-1 and 1.58 (95% CI: 1.14–2.21) for Sat2. A dose–response pattern was found for the risk of DYS and LINE-1 hypomethylation (P-trend < 0.001). Further stratified analysis indicated that the frequency of LINE-1 or Sat2 hypomethylation was higher in subjects with Helicobacter pylori infection. The ORs were 1.83 (95% CI: 1.12–2.99) for LINE-1 and 1.44 (95% CI: 1.01–2.05) for Sat2. The follow-up data indicated that the risk of progression to GC was increased in intestinal metaplasia (IM) subjects with LINE-1 hypomethylation (OR = 2.82; 95% CI: 1.17–6.77) or Sat2 hypomethylation (OR = 2.78; 95% CI: 1.15–6.74). The risk of progression to GC was also increased in DYS subjects with Sat2 hypomethylation (OR = 5.24; 95% CI: 2.00–13.74).ConclusionsThese findings suggest that hypomethylation of repetitive elements in blood leukocytes is associated with the risks of advanced gastric lesions and development of GC.     

Type II diabetes and metabolic syndrome in relation to head and neck squamous cell carcinoma risk: A SEER-Medicare database study

BackgroundDiabetes and metabolic syndrome have been found to increase the risk of various cancers. Previous studies indicated that diabetes may increase the risk of head and neck squamous cell carcinoma (HNSCC). Metabolic syndrome has not been investigated as a risk factor. We tested whether type II diabetes or metabolic syndrome were associated with HNSCC using a very large database of medical administrative records, providing the ability to investigate relatively weak effects and stratify by subgroups.MethodsWe identified persons diagnosed with HNSCC between 1994 and 2007 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We selected controls from a 5% sample of Medicare beneficiaries and frequency matched to cases on sex and duration of enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between type II diabetes/metabolic syndrome and HNSCC, adjusted for potential confounders, among 14,022 cases and 42,066 controls.ResultsWe observed a very weak inverse association between type II diabetes and HNSCC (OR = 0.92; 95% CI, 0.88–0.96) and a moderate inverse association for metabolic syndrome (OR = 0.81; 95% CI, 0.78–0.85). Associations were modified by tobacco use, with null results for type II diabetes among never users (OR = 1.00; 95% CI, 0.95–1.06) and inverse associations among ever users (OR = 0.80; 95% CI, 0.75–0.86).ConclusionsWe observed moderate inverse associations between metabolic syndrome and HNSCC and weak inverse associations between type II diabetes and HNSCC, which was contrary to the evidence to date. Inadequate control for confounding factors, such as overweight/obesity, may have influenced results.     

ERCC1 haplotypes modify bladder cancer risk: A case–control study

Bladder cancer risk is highly influenced by environmental and/or predisposing genetic factors. In the last decades growing evidence of the major role played by DNA repair systems in the developing of bladder cancer has been provided. To better investigate the involvement of DNA repair genes previously reported to be significantly associated with bladder cancer risk, we examined in a case–control study (456 cases and 376 hospital controls) 36 single nucleotide polymorphisms (SNPs) in 10 DNA repair genes, through a better gene coverage and a deep investigation of the haplotype role. A single SNP analysis showed a significantly increased risk given by XRCC1-rs915927 G allele (OR = 1.55, CI 95% 1.02–2.37 for dominant model) and a protective effect of the rare alleles of 3 ERCC1 SNPs: rs967591 (OR = 0.66, CI 95% 0.46–0.95), rs735482 (OR = 0.62, CI 95% 0.42–0.90) and rs2336219 (OR = 0.63, CI 95% 0.43–0.93). Haplotype analysis revealed that cases had a statistically significant excess of XRCC3-TAGT and ERCC1-GAT haplotypes, whereas ERCC1-AAC, MGMT-TA, XRCC1-TGCC and ERCC2-TGAA haplotypes were significantly underrepresented. Together with other published data on large case–control studies, our findings provide epidemiological evidence supporting a link between DNA repair gene variants and bladder cancer development, and suggest that the effects of high-order interactions should be taken into account as modulating factors affecting bladder cancer risk. A detailed characterization of DNA repair genetic variation is warranted and might ultimately help to identify multiple susceptibility variants that could be responsible for joint effects on the risk.     

MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study

BackgroundMicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs.MethodsTwenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels.ResultsDDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR = 1.34 per minor allele; 95% CI: 1.02–1.75), and higher miRNA-222 serum levels nearing statistical significance (MR = 1.21 per minor allele; 95% CI: 0.98–1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR = 0.52; 95% CI: 0.27–0.99). The minor allele of HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR = 1.73 per minor allele; 95% CI: 1.12–2.67), and decreased CNS AIDS-NHL risk (OR = 0.49 per minor allele; 95% CI: 0.25–0.94).ConclusionsThis study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics.     

Seroprevalence and risk factors associated with Toxoplasma gondii in domestic pigs from Spain

Serum samples from 2970 (1400 sows, 1570 fattening) pigs, from 100 farms in the 10 main swine production regions in Spain were tested for antibodies against T. gondii by the modified agglutination test (MAT). Antibodies to T. gondii (MAT 1:25 or higher) were detected in 492 pigs (16.6%, 9.7% in fattening pigs and 24.2% in sows). The herd prevalence was 85.0% (95% CI: 78–92) and within-farm prevalence ranged from 2.9% to 92.8% (median = 17.6%). Statistically significant differences were observed among sampling regions with seroprevalence significantly higher in pigs from Valencia Community (27.3%), Extremadura (23.3%) and Catalonia (21.2%). A generalized estimating equations model indicated that the risk factors associated with T. gondii seroprevalence were: age, sows compared to fattening pigs (OR = 2.9; 95% CI = 1.83–4.53), lack of rodent control (OR = 1.9; 95% CI = 1.04–3.60) and presence of cats (OR = 1.6; 95% CI = 1.12–2.34). The seroprevalence observed in the present study indicates a widespread, although variable, exposure to T. gondii among domestic pigs in Spain, which might have important implications for public health. Management measures including control of rodents and cats on the farms could help to reduce the observed prevalence levels in Spain.     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.     

Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population

Background: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA. Methods: A population-based study was conducted in 3 counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of GC in China. We investigated the association of polymorphisms IVS12?6T>C and IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene–lifestyle interaction. Results: The risk of GC was found to be associated with the IVS12?6C allele (CC vs TT, OR = 2.34, 95% CI: 1.17–4.71) and IVS10+12A allele (GA or AA vs GG, OR = 1.55, 95% CI: 1.14–2.21; and GA vs GG, OR = 1.51, 95% CI: 1.04–2.17). Stratified analysis indicated that an increased risk of GC also was observed in: suspected familial subjects carrying the IVS12?6T>C (OR = 1.68, 95% CI: 1.27–2.66) or IVS10+12G>A (OR = 2.57, 95% CI: 1.53–4.10); or younger subjects carrying the IVS12?6T>C (OR = 2.15, 95% CI: 1.24–3.91) or IVS10+12G>A (OR = 2.23, 95% CI: 1.20–4.33); or male subjects carrying the IVS10+12G>A (OR = 1.64; 95% CI: 1.10–2.54). Furthermore, the combined IVS12?6CC and IVS10+12AA genotypes also significantly increased the risk of GC (OR = 2.12, 95% CI: 1.22–3.66). Statistically significant interactions were observed between: IVS10+12G>A and drinking, high pickled food or fried food intake (OR = 2.32; 95% CI: 1.43–3.78, OR = 2.55; 95% CI: 1.48–4.21 and OR = 2.88; 95% CI: 1.70–4.94, respectively); and IVS12?6T>C and high pickled food intake or fried food intake (OR = 2.65; 95% CI: 1.62–4.47 and OR = 2.48; 95% CI: 1.42–4.13, respectively). Conclusion: The IVS10+12G>A and IVS12?6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.     

Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: A meta-analysis

Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. Results: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR = 1.20, 95% CI = 1.03–1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI = 1.09–1.58) and 1.03 in Asians (95% CI = 0.81–1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR = 1.13, 95% CI = 0.80–1.60, nonsmokers: OR = 0.99, 95% CI = 0.71–1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR = 1.50, 95% CI = 1.09–2.07), but not in colon cancer (OR = 1.33, 95% CI = 0.94–1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. Conclusion: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians.     

Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa

BackgroundThe Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population.MethodsIncident cases (n = 670) of OC and controls (n = 1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models.ResultsA monotonic dose-response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14 g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR = 4.36, 95% CI 2.24–8.48; females OR = 4.56, 95% CI 1.46–14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53 g of ethanol per day had approximately 5-times greater odds in comparison to non-drinkers (males OR = 4.72, 95% CI 2.64–8.41; females OR = 5.24, 95% CI 3.34–8.23) and 8.5 greater odds in those who smoked >14 g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined.ConclusionTobacco and alcohol use are major risk factors for OC development in this region.ImpactThis study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development.