Estimation of the Probability of Exposure to Machining Fluids in a Population-Based Case-Control Study

<div><p>We describe an approach for estimating the probability that study subjects were exposed to metalworking fluids (MWFs) in a population-based case-control study of bladder cancer. Study subject reports on the frequency of machining and use of specific MWFs (straight, soluble, and synthetic/semi-synthetic) were used to estimate exposure probability when available. Those reports also were used to develop estimates for job groups, which were then applied to jobs without MWF reports. Estimates using both cases and controls and controls only were developed. The prevalence of machining varied substantially across job groups (0.1–>0.9%), with the greatest percentage of jobs that machined being reported by machinists and tool and die workers. Reports of straight and soluble MWF use were fairly consistent across job groups (generally 50–70%). Synthetic MWF use was lower (13–45%). There was little difference in reports by cases and controls vs. controls only. Approximately, 1% of the entire study population was assessed as definitely exposed to straight or soluble fluids in contrast to 0.2% definitely exposed to synthetic/semi-synthetics. A comparison between the reported use of the MWFs and U.S. production levels found high correlations (r generally >0.7). Overall, the method described here is likely to have provided a systematic and reliable ranking that better reflects the variability of exposure to three types of MWFs than approaches applied in the past.</p><p>[Supplementary materials are available for this article. Go to the publisher's online edition of <i>Journal of Occupational and Environmental Hygiene</i> for the following free supplemental resources: a list of keywords in the occupational histories that were used to link study subjects to the metalworking fluids (MWFs) modules; recommendations from the literature on selection of MWFs based on type of machining operation, the metal being machined and decade; popular additives to MWFs; the number and proportion of controls who reported various MWF responses by job group; the number and proportion of controls assigned to the MWF types by job group and exposure category; and the distribution of cases and controls assigned various levels of probability by MWF type.]</p></div

Summary of genes in the Clathrin-mediated vesicle pathways used for pathway-based analysis of multi-study bladder cancer GWAS.

1<p>Number of SNPs genotyped in the gene region (20 kb 5′ upstream and 10 kb 3′ downstream from the gene's coding region).</p>2<p>The SNP representing the gene in the pathway analysis after the removal of SNPs with heterogeneous effects.</p>3<p>The rank of the SNP among all SNPs in the gene's region based on their p-values.</p>4<p>Minor allele frequency among controls.</p>5<p>Per allele odds ratios +95% confidence intervals from logistic regression models adjusting for age, sex, study center, DNA source, and smoking.</p>6<p>1 d.f. trend test.</p

Summary of genes in the aromatic amine metabolism pathway used for pathway-based analysis of multi-study bladder cancer GWAS.

1<p>Number of SNPs genotyped in the gene region (20 kb 5′ upstream and 10 kb 3′ downstream from the gene's coding region).</p>2<p>The SNP representing the gene in the pathway analysis after the removal of SNPs with heterogeneous effects.</p>3<p>The rank of the SNP among all SNPs in the gene's region based on their p-values.</p>4<p>Minor allele frequency among controls.</p>5<p>Per allele odds ratios +95% confidence intervals from logistic regression models adjusting for age, sex, study center, DNA source , and smoking.</p>6<p>1 d.f. trend test.</p

Summary of genes in the NAD metabolism pathways used for pathway-based analysis of multi-study bladder cancer GWAS.

1<p>Number of SNPs genotyped in the gene region (20 kb 5′ upstream and 10 kb 3′ downstream from the gene's coding region).</p>2<p>The SNP representing the gene in the pathway analysis after the removal of SNPs with heterogeneous effects.</p>3<p>The rank of the SNP among all SNPs in the gene's region based on their p-values.</p>4<p>Minor allele frequency among controls.</p>5<p>Per allele odds ratios +95% confidence intervals from logistic regression models adjusting for age, sex, study center, DNA source , and smoking.</p>6<p>1 d.f. trend test.</p

Summary of genes in the Mitotic Metaphase/Anaphase Transition pathway used for pathway-based analysis of multi-study bladder cancer GWAS.

1<p>Number of SNPs genotyped in the gene region (20 kb 5′ upstream and 10 kb 3′ downstream from the gene's coding region).</p>2<p>The SNP representing the gene in the pathway analysis after the removal of SNPs with heterogeneous effects.</p>3<p>The rank of the SNP among all SNPs in the gene's region based on their p-values.</p>4<p>Minor allele frequency among controls.</p>5<p>Per allele odds ratios +95% confidence intervals from logistic regression models adjusting for age, sex, study center, DNA source , and smoking.</p>6<p>1 d.f. trend test.</p

Pathways enriched with bladder cancer susceptibility loci at a <i>P</i>≤0.01 level using GSEA and ARTP.

<p>Results of the top ranked pathways (<i>P</i><0.01) using GSEA and ARTP. In parenthesis are results prior of removal SNPs displaying heterogeneous signals.</p>1<p>The number of genes in the pathway.</p>2<p>The number of genes underlying the enrichment signal in the pathway.</p>3<p><i>P</i>-value of the enrichment score based on 10,000 permutations.</p>4<p>False-discovery rate calculated based on the normalized statistics of the permutation data to account for the variable sizes of genes and pathways.</p