Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients.

BACKGROUND: Aberrant Wnt signaling activation occurs commonly in colorectal carcinogenesis, leading to upregulation of many target genes. APC (adenomatous polyposis coli) is an important component of the ß-catenin destruction complex, which regulates Wnt signaling, and is often mutated in colorectal cancer (CRC). In addition to mutational events, epigenetic changes arise frequently in CRC, specifically, promoter hypermethylation which silences tumor suppressor genes. APC and the Wnt signaling target gene ITF2 (immunoglobulin transcription factor 2) incur hypermethylation in various cancers, however, methylation-dependent regulation of these genes in CRC has not been studied in large, well-characterized patient cohorts. The microsatellite instability (MSI) subtype of CRC, featuring DNA mismatch repair deficiency and often promoter hypermethylation of MutL homolog 1 (MLH1), has a favorable outcome and is characterized by different chemotherapeutic responses than microsatellite stable (MSS) tumors. Other epigenetic events distinguishing these subtypes have not yet been fully elucidated. METHODS: Here, we quantify promoter methylation of ITF2 and APC by MethyLight in two case-case studies nested in population-based CRC cohorts from the Ontario Familial Colorectal Cancer Registry (n = 330) and the Newfoundland Familial Colorectal Cancer Registry (n = 102) comparing MSI status groups. RESULTS: ITF2 and APC methylation are significantly associated with tumor versus normal state (both P < 1.0 × 10(-6)). ITF2 is methylated in 45.8% of MSI cases and 26.9% of MSS cases and is significantly associated with MSI in Ontario (P = 0.002) and Newfoundland (P = 0.005) as well as the MSI-associated feature of MLH1 promoter hypermethylation (P = 6.72 × 10(-4)). APC methylation, although tumor-specific, does not show a significant association with tumor subtype, age, gender, or stage, indicating it is a general tumor-specific CRC biomarker. CONCLUSIONS: This study demonstrates, for the first time, MSI-associated ITF2 methylation, and further reveals the subtype-specific epigenetic events modulating Wnt signaling in CRC.

Comparison of Field Measurements to Methane Emissions Models at a New Landfill.

Estimates of methane emissions from landfills rely primarily on models due to both technical and economic limitations. While models are easy to implement, there is uncertainty due to the use of parameters that are difficult to validate. The objective of this research was to compare modeled emissions using several greenhouse gas (GHG) emissions reporting protocols including: (1) Intergovernmental Panel on Climate Change (IPCC); (2) U.S. Environmental Protection Agency Greenhouse Gas Reporting Program (EPA GHGRP); (3) California Air Resources Board (CARB); and (4) Solid Waste Industry for Climate Solutions (SWICS), with measured emissions data collected over three calendar years from a young landfill with no gas collection system. By working with whole landfill measurements of fugitive methane emissions and methane oxidation, the collection efficiency could be set to zero, thus eliminating one source of parameter uncertainty. The models consistently overestimated annual methane emissions by a factor ranging from 4-31. Varying input parameters over reasonable ranges reduced this range to 1.3-8. Waste age at the studied landfill was less than four years and the results suggest the need for measurements at additional landfills to evaluate the accuracy of the tested models to young landfills.

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24.

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.

Genome-wide DNA methylation study of hip and knee cartilage reveals embryonic organ and skeletal system morphogenesis as major pathways involved in osteoarthritis.

BACKGROUND: Evidence suggests that epigenetics plays a role in osteoarthrits (OA). The aim of the study was to describe the genome wide DNA methylation changes in hip and knee OA and identify novel genes and pathways involved in OA by comparing the DNA methylome of the hip and knee osteoarthritic cartilage tissues with those of OA-free individuals. METHODS: Cartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls. DNA was extracted from the collected cartilage and assayed by Illumina Infinium HumanMethylation450 BeadChip array, which allows for the analysis of >480,000 CpG sites. Student T-test was conducted for each CpG site and those sites with at least 10 % methylation difference and a p value <0.0005 were defined as differentially methylated regions (DMRs) for OA. A sub-analysis was also done for hip and knee OA separately. DAVID v6.7 was used for the functional annotation clustering of the DMR genes. Clustering analysis was done using multiple dimensional scaling and hierarchical clustering methods. RESULTS: The study included 5 patients with hip OA, 6 patients with knee OA and 7 hip cartilage samples from OA-free individuals. The comparisons of hip, knee and combined hip/knee OA patients with controls resulted in 26, 72, and 103 DMRs, respectively. The comparison between hip and knee OA revealed 67 DMRs. The overall number of the sites after considering the overlaps was 239, among which 151 sites were annotated to 145 genes. One-fifth of these genes were reported in previous studies. The functional annotation clustering of the identified genes revealed clusters significantly enriched in skeletal system morphogenesis and development. The analysis revealed significant difference among OA and OA-free cartilage, but less different between hip OA and knee OA. CONCLUSIONS: We found that a number of CpG sites and genes across the genome were differentially methylated in OA patients, a remarkable portion of which seem to be involved in potential etiologic mechanisms of OA. Genes involved in skeletal developmental pathways and embryonic organ morphogenesis may be a potential area for further OA studies.

Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Labrador and Ontario, Canada.

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.

Underwater optical wireless communications: depth-dependent beam refraction.

Global refractive gradients in seawater cause pointing problems for optical wireless communications. A refractive index depth profile of the Pacific Ocean was calculated from measured salinity, temperature, and pressure, determining the end points of a refracted and nonrefracted 200 m communication link. Numerical ray tracing was used with a point source for angles between 10° and 80° and transmission wavelengths of 500-650 nm; the maximum end-point difference found was 0.23 m. A 500 nm laser with a 0.57° full-angle FOV was traced; the nonrefracted receiver location was outside the FOV for all links angled >15° to the vertical. However, most pointing issues underwater are unlikely to be significant with suitable FOV choice and natural scattering of the source.

Underwater optical wireless communications: depth dependent variations in attenuation.

Depth variations in the attenuation coefficient for light in the ocean were calculated using a one-parameter model based on the chlorophyll-a concentration C(c) and experimentally-determined Gaussian chlorophyll-depth profiles. The depth profiles were related to surface chlorophyll levels for the range 0-4 mg/m², representing clear, open ocean. The depth where C(c) became negligible was calculated to be shallower for places of high surface chlorophyll; 111.5 m for surface chlorophyll 0.8

Estimation of total landfill surface methane emissions using geospatial approach combined with measured surface ambient air methane concentrations.

The concentration of surface air methane (CH4) measured in parts per million by volume (ppmv) near the soil/atmosphere interface should, in theory, have a positive correlation with surface methane emissions fluxes, measured in grams per square meter per day (gm-2d-1). Some researchers suggest that CH4 flux can be reasonably inferred from simple measurements of CH4 concentrations near the landfill surface. Ground-based and drone-based surface emissions monitoring (SEMs) were performed at several municipal solid waste landfills as tracer correlation method (TCM) testing was being used to measure total methane emissions from the same landfills. The TCM data and SEM data were used to establish a new simple correlation to convert surface methane concentrations in ppmv to localized surface methane emission flux in gm-2d-1.The SEM data obtained from ten ground and drone monitoring campaigns were log-transformed and geospatially treated using inverse distance weighting to the power of 2 to predict methane surface concentrations in the entire footprint of the SEM measurements area. The developed new correlation equation was then used to convert every predicted surface methane concentration to an emissions flux. The total estimate of surface emissions from the entire landfill was obtained by integrating the predicted fluxes over the area of the footprint of the SEM measurement area. The use of the new developed correlation resulted in higher total emissions estimates than other correlations reported in the literature and should be considered more conservative. Not including other factors, the proposed approach provides estimate of total methane emissions with a coefficient of variation of 20%. This study introduces a novel approach that utilizes a developed correlation between surface methane concentrations and surface emissions fluxes to estimate total methane emissions from municipal solid waste landfills or from a specified area. This study provides an additional use of the quarterly SEM data.Implications: The proposed approach provides an occasion for additional use of the easily obtainable quarterly SEMs data that can be performed by most landfills. The SEMs data are the most abundant landfill methane concentrations data. This approach gives them more benefit for the user. It is intended to convert ambient air concentrations to some estimates of surface emissions that can help landfill owners with decision making such as remediation activities or adjustments of their gas collection a systems.

Inherited deleterious variants in GALNT12 are associated with CRC susceptibility.

A recent report detailed the occurrence of both somatic and constitutional variants in the GALNT12 gene, located at 9q22.33, in some colorectal cancer (CRC) patients. In this study, we investigate the occurrence of inherited deleterious variants in GALNT12 in 118 families referred to a cancer genetics clinic. We discovered two deleterious variants (c.907G>A (p.Asp303Asn); c.1187A>G (p.Tyr396Cys)) in 4/118 probands. The variants, which were not found in 149 control individuals (P = 0.0376), cosegregate with CRC and/or adenomatous polyps in other family members. The probability by chance that cosegregation of c.907G>A with CRC and/or adenomatous polyps occurred, in the two pedigrees combined, was 1.56%. Although this study does not provide irrefutable evidence that GALNT12 variants are highly penetrant alleles that predispose to CRC in the majority of unexplained hereditary CRC families, it does provide additional evidence to support an important role of these variants in a proportion of this considerable high-risk group.

Meta-analysis of new genome-wide association studies of colorectal cancer risk.

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients.

Diet and lifestyle influence colorectal cancer (CRC) risk but the molecular events that mediate these effects are poorly characterized. Several dietary and lifestyle factors can modulate DNA methylation suggesting that they may influence CRC risk through epigenetic regulation of cancer-related genes. The Wnt regulatory genes DKK1 and Wnt5a are important contributors to colonic carcinogenesis and are often silenced by promoter hypermethylation in CRC; however, the dietary contributions to these events have not been explored. To investigate the link between dietary/lifestyle factors and epigenetic regulation of these Wnt signaling genes, we assessed promoter methylation of these genes in a large cohort of Canadian CRC patients from Ontario (n = 549) and Newfoundland (n = 443) and examined associations to dietary/lifestyle factors implicated in CRC risk and/or DNA methylation including intake of vitamins, fats, cholesterol, fiber, and alcohol as well as body mass index (BMI), and smoking status. Several factors were associated with methylation status including alcohol intake, BMI, and cigarette smoking. Most significantly, however, dietary vitamin D intake was strongly negatively associated with DKK1 methylation in Newfoundland (P = 0.001) and a similar trend was observed in Ontario. These results suggest that vitamin D and other dietary/lifestyle factors may alter CRC risk by mediating extracellular Wnt inhibition.

A new approach to characterize emission contributions from area sources during optical remote sensing technique testing.

UNLABELLED: In the method termed "Other Test Method-10," the U.S. Environmental Protection Agency has proposed a method to quantify emissions from nonpoint sources by the use of vertical radial plume mapping (VRPM) technique. The surface area of the emitting source and the degree to which the different zones of the emitting source are contributing to the VRPM computed emissions are often unknown. The objective of this study was to investigate and present an approach to quantify the unknown emitting surface area that is contributing to VRPM measured emissions. Currently a preexisting model known as the "multiple linear regression model," which is described in Thoma et al. (2009), is used for quantifying the unknown surface area. The method investigated and presented in this paper utilized tracer tests to collect data and develop a model much like that described in Thoma et al. (2009). However unlike the study used for development of the multiple linear regression model, this study is considered a very limited study due to the low number of pollutant releases performed (seven total releases). It was found through this limited study that the location of an emitting source impacts VRPM computed emissions exponentially, rather than linearly (i.e., the impact that an emitting source has on VRPM measurements decreases exponentially with increasing distances between the emitting source and the VRPM plane). The data from the field tracer tests were used to suggest a multiple exponential regression model. The findings of this study, however, are based on a very small number of tracer tests. More tracer tests performed during all types of climatic conditions, terrain conditions, and different emissions geometries are still needed to better understand the variation of capture efficiency with emitting source location. This study provides a step toward such an objective. IMPLICATIONS: The findings of this study will aid in the advancement of the VRPM technique. In particular, the contribution of this study is to propose a slight improvement in how the area contributing to flux is determined during VRPM campaigns. This will reduce some of the technique's inherent uncertainties when it is employed to estimate emissions from an area source under nonideal conditions.

Methane emissions from 20 landfills across the United States using vertical radial plume mapping.

Landfill fugitive methane emissions were quantified as a function of climate type and cover type at 20 landfills using US. Environmental Protection Agency (EPA) Other Test Method (OTM)-10 vertical radial plume mapping (VRPM) with tunable diode lasers (TDLs). The VRPM data were initially collected as g CH4/sec emission rates and subsequently converted to g CH4/m2/ day rates using two recently published approaches. The first was based upon field tracer releases of methane or acetylene and multiple linear regression analysis (MLRM). The second was a virtual computer model that was based upon the Industrial Source Complex (ISC3) and Pasquill plume stability class models (PSCMs). Calculated emission results in g CH4/m2/day for each measured VRPM with the two approaches agreed well (r2 = 0.93). The VRPM data were obtained from the working face, temporary soil, intermediate soil, and final soil or synthetic covers. The data show that methane emissions to the atmosphere are a function of climate and cover type. Humid subtropical climates exhibited the highest emissions for all cover types at 207, 127, 102, and 32 g CH4/m2/day, for working face (no cover), temporary, intermediate, and final cover, respectively. Humid continental warm summers showed 67, 51, and 27 g CH4/m2/day for temporary, intermediate, and final covers. Humid continental cool summers were 135, 40, and 26 g CH4/m2/day for the working face, intermediate, and final covers. Mediterranean climates were examined for intermediate and final covers only and found to be 11 and 6 g CH4/m2/day, respectively, whereas semiarid climates showed 85, 11, 3.7, and 2.7 g CH4/m2/day for working face, temporary, intermediate, and final covers. A closed, synthetically capped landfill covered with soil and vegetation with a gas collection system in a humid continental warm summer climate gave mostly background methane readings and average emission rates of only 0.09 g CH4/m2/day flux when measurable.

Promoter methylation of Wnt antagonists DKK1 and SFRP1 is associated with opposing tumor subtypes in two large populations of colorectal cancer patients.

Aberrant activation of canonical Wnt signaling is a hallmark event in colorectal carcinogenesis. The Dickkopf-1 (DKK1) and Secreted Frizzled Related Protein 1 (SFRP1) genes encode extracellular inhibitors of Wnt signaling that are frequently silenced by promoter hypermethylation in colorectal cancer (CRC). These methylation events have been identified as prognostic markers of patient outcome and tumor subtype in several cancers but similar roles in CRC have not been comprehensively examined. In CRC, the microsatellite instability (MSI) subtype associates with favorable disease outcome but the molecular events that are responsible remain poorly understood. Consequently, we quantified promoter methylation status of the Wnt antagonist genes DKK1 and SFRP1 in a large population-based cohort of CRCs from Ontario (n = 549) and Newfoundland (n = 696) stratified by MSI status. We examined the association between methylation status and clinicopathological features including tumor MSI status and patient survival. DKK1 and SFRP1 were methylated in 13 and 95% of CRCs, respectively. In Ontario, DKK1 methylation was strongly associated with MSI tumors after adjustment for age, sex and tumor location [odds ratio (OR) = 13.7, 95% confidence interval (CI) = 7.8-24.2, P < 0.001]. Conversely, SFRP1 methylation was inversely associated with MSI tumors after these adjustments (OR = 0.3, 95% CI = 0.1-0.9, P = 0.009). Similar results were obtained in Newfoundland. There were no independent associations with recurrence-free survival. This is the first large study to identify associations between Wnt antagonist promoter hypermethylation and CRC MSI subtype. These events provide insight into subtype-specific epigenetic mediation of Wnt signaling in CRC.

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer.

Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4% (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7% (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3% (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.

Landfill methane oxidation across climate types in the U.S.

Methane oxidation in landfill covers was determined by stable isotope analyses over 37 seasonal sampling events at 20 landfills with intermediate covers over four years. Values were calculated two ways: by assuming no isotopic fractionation during gas transport, which produces a conservative or minimum estimate, and by assuming limited isotopic fractionation with gas transport producing a higher estimate. Thus bracketed, the best assessment of mean oxidation within the soil covers from chamber captured emitted CH(4) was 37.5 ± 3.5%. The fraction of CH(4) oxidized refers to the fraction of CH(4) delivered to the base of the cover that was oxidized to CO(2) and partitioned to microbial biomass instead of being emitted to the atmosphere as CH(4) expressed as a percentage. Air samples were also collected at the surface of the landfill, and represent CH(4) from soil, from leaking infrastructure, and from cover defects. A similar assessment of this data set yields 36.1 ± 7.2% oxidation. Landfills in five climate types were investigated. The fraction oxidized in arid sites was significantly greater than oxidation in mediterranean sites, or cool and warm continental sites. Sub tropical sites had significantly lower CH(4) oxidation than the other types of sites. This relationship may be explained by the observed inverse relationship between cover loading and fractional CH(4) oxidation.

Calcium and vitamin D and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland and Labrador and Ontario.

BACKGROUND: Previous epidemiological studies have been suggestive but inconclusive in demonstrating inverse associations of calcium, vitamin D, dairy product intakes with risk of colorectal cancer (CRC). We conducted a large population-based comparison of such associations in Newfoundland and Labrador (NL) and Ontario (ON). METHODS: A case control study design was used. Colorectal cancer cases were new CRC patients aged 20-74 years. Controls were a sex and age-group matched random sample of the population in each province. 1760 cases and 2481 controls from NL and ON were analyzed. Information on dietary intake and lifestyle was collected using self-administered food frequency and personal history questionnaires. RESULTS: Controls reported higher mean daily intakes of total calcium and total vitamin D than cases in both provinces. In ON, significant reduced CRC risk was associated with intakes of total calcium (OR of highest vs. lowest quintiles was 0.57, 95% CI 0.42-0.77, p(trend) = 0.03), total vitamin D (OR = 0.73, 95% CI 0.54-1.00), dietary calcium (OR = 0.76, 95% CI 0.60-0.97), dietary vitamin D (OR = 0.77, 95% CI 0.61-0.99), total dairy products and milk (OR = 0.78, 95% CI 0.60-1.00), calcium-containing supplements use (OR = 0.76). In NL, the inverse associations of calcium, vitamin D with CRC risk were most pronounced among calcium- or vitamin D-containing supplement users (OR = 0.67, 0.68, respectively). CONCLUSIONS: Results of this study add to the evidence that total calcium, dietary calcium, total vitamin D, dietary vitamin D, calcium- or vitamin D-containing supplement use may reduce the risk of CRC. The inverse associations of CRC risk with intakes of total dairy products and milk may be largely due to calcium and vitamin D.

Sampling state and process variables on coral reefs.

Contemporary coral reefs are forced to survive through and recover from disturbances at a variety of spatial and temporal scales. Understanding disturbances in the context of ecological processes may lead to accurate predictive models of population trajectories. Most coral-reef studies and monitoring programs examine state variables, which include the percentage coverage of major benthic organisms, but few studies examine the key ecological processes that drive the state variables. Here we outline a sampling strategy that captures both state and process variables, at a spatial scale of tens of kilometers. Specifically, we are interested in (1) examining spatial and temporal patterns in coral population size-frequency distributions, (2) determining major population processes, including rates of recruitment and mortality, and (3) examining relationships between processes and state variables. Our effective sampling units are randomly selected 75 × 25 m stations, spaced approximately 250-500 m apart, representing a 10(3) m spatial scale. Stations are nested within sites, spaced approximately 2 km apart, representing a 10(4) m spatial scale. Three randomly selected 16 m(2) quadrats placed in each station and marked for relocation are used to assess processes across time, while random belt-transects, re-randomized at each sampling event, are used to sample state variables. Both quadrats and belt-transects are effectively sub-samples from which we will derive estimates of means for each station at each sampling event. This nested sampling strategy allows us to determine critical stages in populations, examine population performance, and compare processes through disturbance events and across regions.

Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study.

BACKGROUND & AIMS: The MutY human homologue (MYH) gene is a member of the base-excision repair pathway involved in the repair of oxidative DNA damage. The objective of this study was to determine colorectal cancer (CRC) risk associated with mutations in the MYH gene. METHODS: A total of 3811 CRC cases and 2802 controls collected from a multisite CRC registry were screened for 9 germline MYH mutations; subjects with any mutation underwent screening of the entire MYH gene. Logistic regression was used to estimate age- and sex-adjusted odds ratios (AOR). Clinicopathologic and epidemiologic data were reviewed to describe the phenotype associated with MYH mutation status and assess for potential confounding and effect modification. RESULTS: Twenty-seven cases and 1 control subject carried homozygous or compound heterozygous MYH mutations (AOR, 18.1; 95% confidence interval, 2.5-132.7). CRC cases with homozygous/compound heterozygous mutations were younger at diagnosis (P=.01), had a higher proportion of right-sided (P=.01), synchronous cancers (P<.01), and personal history of adenomatous polyps (P=.003). Heterozygous MYH mutations were identified in 87 CRC cases and 43 controls; carriers were at increased risk of CRC (AOR, 1.48; 95% confidence interval, 1.02-2.16). There was a higher prevalence of low-frequency microsatellite instability (MSI) in tumors from heterozygous and homozygous/compound heterozygous MYH mutation carriers (P=.02); MSI status modified the CRC risk associated with heterozygous MYH mutations (P interaction<.001). CONCLUSIONS: Homozygous/compound heterozygous MYH mutations account for less than 1% of CRC cases. Heterozygous carriers are at increased risk of CRC. Further studies are needed to understand the possible interaction between the base excision repair and low-frequency MSI pathways.

Uncertainties associated with the use of optical remote sensing technique to estimate surface emissions in landfill applications.

Landfills represent a source of distributed emissions source over an irregular and heterogeneous surface. In the method termed "Other Test Method-10" (OTM-10), the U.S. Environmental Protection Agency (EPA) has proposed a method to quantify emissions from such sources by the use of vertical radial plume mapping (VRPM) techniques combined with measurement of wind speed to determine the average emission flux per unit area per time from nonpoint sources. In such application, the VRPM is used as a tool to estimate the mass of the gas of interest crossing a vertical plane. This estimation is done by fitting the field-measured concentration spatial data to a Gaussian or some other distribution to define a plume crossing the vertical plane. When this technique is applied to landfill surfaces, the VRPM plane may be within the emitting source area itself. The objective of this study was to investigate uncertainties associated with using OTM-10 for landfills. The spatial variability of emission in the emitting domain can lead to uncertainties of -34 to 190% in the measured flux value when idealistic scenarios were simulated. The level of uncertainty might be higher when the number and locations of emitting sources are not known (typical field conditions). The level of uncertainty can be reduced by improving the layout of the VRPM plane in the field in accordance with an initial survey of the emission patterns. The change in wind direction during an OTM-10 testing setup can introduce an uncertainty of 20% of the measured flux value. This study also provides estimates of the area contributing to flux (ACF) to be used in conjunction with OTM-10 procedures. The estimate of ACF is a function of the atmospheric stability class and has an uncertainty of 10-30%.