Charles S., "Interleukin-1 polymorphisms associated with increased risk of gastric cancer" (2000). To evaluate dopaminergic cells of the dorsomedial cluster by tyrosine hydroxylase immunostaining, serial 4-mm sections were cut to include the entire brain. Immunopositive cells at the level of the giant interneuron commissure, posterior to the fan-shaped body, were counted in well oriented frontal sections at 1, 10, 30 and 60 days. At 1 day all control and experimental sections contained four or ®ve cells in the delineated region. At 30 and 60 days all controls showed four or ®ve cells. At 30 and 60 days all a-synucleinexpressing animals (a-synuclein, elav±GAL4 and a-synuclein, Ddc±GAL4 transheterozygotes) showed 0 or 1 tyrosine-hydroxylase-positive cell in the de®ned region. Tyrosinehydroxylase-positive cells outside the dorsomedial cluster were present, and served as internal controls for the immunostaining procedure. At least four, and usually between six and ten brains were examined for wild-type a-synuclein and each mutant a-synuclein. Controls included young and aged¯ies of the genotypes elav±GAL4/+ and Ddc±GAL4/+. We evaluated expression of a-synuclein and b-galactosidase on similar serial section preparations. Quanti®cation was simpli®ed in these experiments because no clear cellbody-associated a-synuclein or b-galactosidase immunoreactivity was observed in the aged a-synuclein transgenic¯ies at the times reported.For histological examination of retinas, heads were ®xed in glutaraldehyde and embedded in epon. Tangential retinal sections were prepared at a thickness of 1 mm and stained with toluidine blue (Fig 4).Standard electron microscopy was performed on brains from 25-day-old experimental (UAS±A30P a-synuclein/elav±GAL4) and control (elav±GAL4/+)¯ies. For immunoelectron microscopy, pre-embedding immunohistochemistry with an Hrp-congugated secondary antibody was performed on 60-day adult brains from experimental (UAS± A30P a-synuclein/elav±GAL4) and control (elav±GAL4/+)¯ies ®xed in 4% paraformaldehyde with 0.5% glutaraldehyde. Tissue was post-®xed in osmium and embedded in epon. Unstained ultrathin sections and ultrathin sections stained with uranyl acetate and lead citrate were examined. Climbing assayThe climbing assay was performed as described 19,20 . Forty¯ies were placed in a plastic vial, and gently tapped to the bottom of the vial. The number of¯ies at the top of the vial was counted after 18 s of climbing. Twenty trials were performed for each time point. The data shown represent results from a cohort of¯ies tested serially over 55 days. The experiment was repeated three times, with independently derived transgenic lines. Similar results were obtained from each experiment. The experiment was carried out under red light (Kodak Safelight Filter 1A). Control¯ies were of the genotype elav±GAL4/+. Experimental animals were of the following genotypes: (1) elav±GAL4/+; UAS±wild-type a-synuclein/+; (2) UAS±A30P a-synuclein/elav±GAL4; and (3) UAS±A53T a-synuclein/elav±GAL4.

Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus < or =8 micro g/liter. Compared with subjects not drinking chlorinated water, subjects with THM exposure of >35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.

No abstract

Gliomas account for approximately 80% of all primary malignant brain tumors, and despite improvements in clinical care over the last 20 years remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 casecontrol studies, and 1 population-based case only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo [4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo [4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)-pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma. (Cancer Res 2005; 65(17): 8034-41)

No abstract

BACKGROUND Renal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the U.S. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension–renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence. METHODS Participants were enrolled in a population-based case-control study in Detroit and Chicago during 2002–2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer. RESULTS Hypertension doubled renal cancer risk (OR=2.0 [CI=1.7–2.5]) overall. For whites the OR was 1.9 (CI=1.5–2.4), while for blacks it was 2.8 (2.1–3.8) (p for interaction=0.11). ORs increased with time after hypertension diagnosis (p for trend <0.001), reaching 4.1 (CI=2.3–7.4) for blacks and 2.6 (CI=1.7–4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI=2.3–8.8) for blacks and 2.1 (CI=1.2–3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50–79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men. CONCLUSIONS Hypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.