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.

After over two decades of increasing rates, kidney cancer incidence trends worldwide show signs of plateauing or decreases in recent years. In the United States, rates for renal cell cancer, the predominant form of kidney cancer in adults, continue to rise but mainly for early stage tumors. Incidence rates for renal pelvis cancer have declined, while kidney cancer mortality rates overall have leveled. These patterns are consistent with reports of incidental diagnosis and downward shift of tumor stage and size in clinical series. The changing prevalence of known risk factors for renal cell cancer, including cigarette smoking, obesity, and hypertension, may also be influencing the incidence trends, although their relative impact may differ in various populations,. Evidence is accumulating to suggest an etiologic role for physical activity, alcohol consumption, occupational exposure to trichloroethylene, and high parity among women, but causal conclusions are not yet supported. Genetic susceptibility and its interaction with environmental exposures are believed to influence renal cell cancer risk, but limited studies based on candidate gene approaches have not produced conclusive results. Large consortium efforts employing genome-wide scanning technology are underway, which hold promise for novel discoveries in renal carcinogenesis.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases.

We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×10−9; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.

In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.

Higher body-mass index and elevated blood pressure independently increase the long-term risk of renal-cell cancer in men. A reduction in blood pressure lowers the risk.

Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explore the temporal patterns among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program for 22,759 esophageal cancer cases, of which 9,526 cases were adenocarcinoma, diagnosed from January 1, 1975, through December 31, 2004. Among white men, increases in the incidence of esophageal cancer were largely attributed to the 463% increase in the incidence of adenocarcinoma from 1.01 per 100,000 person-years in 1975−1979 to 5.69 per 100,000 person-years in 2000−2004 (95% confidence intervals [CI]=0.90 to 1.13 and 5.47 to 5.91, respectively). A similar rapid increase is now clearly apparent among white women, among whom the adenocarcinoma rate increased 335% from 0.17 to 0.74 per 100,000 person-years (95% CI= 0.13 to 0.21 and 0.67 to 0.81, respectively) over the same time period. Adenocarcinoma rates rose among white men and women regardless of stage and age groups, indicating that these increases are real and not an artifact of surveillance.

Although cancer is a major cause of morbidity and mortality in most nations, the spectrum of cancer occurrence varies substantially worldwide. Most previous epidemiologic studies investigating cancer etiology were conducted in North American and western European countries that are relatively homogenous in terms of cancer spectrums and many lifestyle exposures. These limitations may have hindered these studies from evaluating some important etiologic hypotheses. From 1996 to 2000, the Shanghai Women's Health Study recruited 74,942 adult Chinese women from selected urban communities, with a 92% response rate. All participants completed a detailed baseline survey and anthropometrics. Approximately 88% of cohort members donated a urine sample (n = 65,755) and a blood (n = 56,832) or exfoliated buccal cell (n = 8,934) sample. Noteworthy characteristics of this cohort include low consumption of alcohol (1.9%) and use of tobacco (2.4%); high intake of fish (mean, 50.8 g/day), soy foods (mean, 142.3 g/day), and certain vegetables; low prevalence of obesity (5.1%); and nearly 100% employment outside the home. Currently, this cohort of women is being followed via biennial in-person recontact and periodic linkage to cancer and vital statistics registries. The resources from the cohort will be valuable in future studies of environmental exposures and biomarkers for the risk of cancer and other chronic diseases.