Age-adjusted odds ratio (AOR) estimates for total alcohol consumption and alcohol type.

<p><b>Abbreviations:</b> AOR: age-adjusted odds ratio (assessment of covariates showed no confounders), CI: confidence interval</p><p>^a 2 years prior to diagnosis/questionnaire completion</p><p>^b Beer, red wine, white wine, and liquor consumption was never or less than once per month</p><p>Age-adjusted odds ratio (AOR) estimates for total alcohol consumption and alcohol type.</p

Description of study participants, including age-adjusted odds ratio (AOR) estimates for pancreatic cancer risk factors.

<p><b>Abbreviations:</b> AOR: age-adjusted odds ratio, CI: confidence interval</p><p>Numbers may not add to total due to missing values</p><p>^a One year before diagnosis/questionnaire completion</p><p>^b Prior to one year before diagnosis/questionnaire completion; Type 2 diabetes</p><p>^c First degree relative</p><p>^d Age at pancreatic cancer diagnosis for cases and age at questionnaire completion for controls</p><p>Description of study participants, including age-adjusted odds ratio (AOR) estimates for pancreatic cancer risk factors.</p

Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk

<div><p>Background</p><p>Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk.</p><p>Methods</p><p>A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants.</p><p>Results</p><p>18 SNPs in 14 candidate genes (<i>CSF2</i>, <i>DENND1B</i>, <i>DPP10</i>, <i>FLG</i>, <i>IL13</i>, <i>IL13RA2</i>, <i>LRP1B</i>, <i>NOD1</i>, <i>NPSR1</i>, <i>ORMDL3</i>, <i>RORA</i>, <i>STAT4</i>, <i>TLR6</i>, <i>TRA</i>) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two <i>LRP1B</i> SNPs remained statistically significant; for example, <i>LRP1B</i> rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007).</p><p>Conclusions</p><p>Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.</p></div

Distribution of pancreatic cancer cases, controls and odds ratios for selected subject characteristics.

<p>Distribution of pancreatic cancer cases, controls and odds ratios for selected subject characteristics.</p

List of vitamin D pathway genes, official gene symbols and number of polymorphisms genotyped.

<p>List of vitamin D pathway genes, official gene symbols and number of polymorphisms genotyped.</p

Age and sex adjusted odds ratios for the associations between SNPs in vitamin D-related genes and pancreas cancer risk among Ontario cases (n = 628) and controls (n = 1193) by genotype categories; results are shown for all SNPs with 95% confidence intervals that do not overlap 1.0.

a<p>rs6013905 is in high linkage disequilibrium with rs4809958 (r² = 0.94).</p>b<p>rs2060793 is in complete linkage disequilibrium with SNP rs2060793 (r² = 1.00); both SNPs were genotyped in our study and results were the same.</p

MLH1 Region Polymorphisms Show a Significant Association with CpG Island Shore Methylation in a Large Cohort of Healthy Individuals

<div><p>Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We previously demonstrated that SNPs (rs1800734, rs749072, and rs13098279) in the <em>MLH1</em> gene region are associated with <em>MLH1</em> promoter island methylation, loss of MLH1 protein expression, and microsatellite instability (MSI) in colorectal cancer (CRC) patients. Recent studies have identified less CpG-dense “shore” regions flanking many CpG islands. These shores often exhibit distinct methylation profiles between different tissues and matched normal versus tumor cells of patients. To date, most epigenetic studies have focused on <em>somatic</em> methylation events occurring within solid tumors; less is known of the contributions of peripheral blood cell (PBC) methylation to processes such as aging and tumorigenesis. To address whether <em>MLH1</em> methylation in PBCs is correlated with tumorigenesis we utilized the Illumina 450 K microarrays to measure methylation in PBC DNA of 846 healthy controls and 252 CRC patients from Ontario, Canada. Analysis of a region of chromosome 3p21 spanning the <em>MLH1</em> locus in healthy controls revealed that a CpG island shore 1 kb upstream of the <em>MLH1</em> gene exhibits different methylation profiles when stratified by SNP genotypes (rs1800734, rs749072, and rs13098279). Individuals with wild-type genotypes incur significantly higher PBC shore methylation than heterozygous or homozygous variant carriers (p<1.1×10⁻⁶; ANOVA). This trend is also seen in CRC cases (p<0.096; ANOVA). Shore methylation also decreases significantly with increasing age in cases and controls. This is the first study of its kind to integrate PBC methylation at a CpG island shore with SNP genotype status in CRC cases and controls. These results indicate that CpG island shore methylation in PBCs may be influenced by genotype as well as the normal aging process.</p> </div

Associations between 87 SNPs in vitamin D-related genes and pancreas cancer risk among Ontario cases (n = 628) and controls (n = 1193) and age and sex adjusted OR using a log additive model

a<p>MAF and HWE were calculated among controls only</p>b<p>Five SNPs (rs11023374, rs1989969, rs2238136, rs2238135, rs2853564) showed significant departure from HWE and were excluded from subsequent analyses</p>c<p>Odds ratios were estimated using logistic regression adjusted for age and sex and assuming a log additive model for each SNP.</p>d<p>Adjusted for multiple comparisons using the False Discovery Rate (FDR).</p

Treatment of the BRCA wt tumor OCIP23 results in accumulation of γH2AX positive nuclei.

<p>Representative images of FFPE sections (n = 4 per group) stained for (A) DNAPK, (B) Ku70, (C) XRCC4 or (D) γH2AX. Bars represent 100μm.</p

Logistic regression analysis for association with methylation between CRC cases and controls.

<p>Mean β value of CRC cases and controls is shown along with logistic regression analysis at seven CpG sites in the <i>MLH1</i> CpG island shore. Analysis of CRC cases versus controls is adjusted for age and sex. Effect size represents the increased risk of CRC per 1% reduction in methylation.</p