Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.
ABSTRACT A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.
Article: Uptake of 14C-chlorpyrifos by clams.[show abstract] [hide abstract]
ABSTRACT: The uptake of 14C-chlorpyrifos by clams (Katalysia opima) was studied to determine the bioaccumulation potential over a period of five days. Chlorpyrifos was applied to a model ecosystem in beakers at the rate of 3 mg l(-1) of seawater. Clams showed a maximum uptake of 14C-chlorpyrifos in the first 8 hours of exposure. Subsequently these residues decreased significantly and at the end of 5 days about 1.5% of the applied activity could be recovered from the clam samples. The half-life of chlorpyrifos in this marine water system was about a day. However, after 5 days about 28% of the applied 14C-activity was present in water. This may be significant and could possibly play a role in finding the residue of this insecticide in water bodies. Clams brought about rapid degradation of chlorpyrifos in the first 48 hours. The stabilised residues in water were reflected later in clams.Environmental Technology 12/2002; 23(11):1309-11. · 1.41 Impact Factor
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ABSTRACT: Genomewide association studies are now a widely used approach in the search for loci that affect complex traits. After detection of significant association, estimates of penetrance and allele-frequency parameters for the associated variant indicate the importance of that variant and facilitate the planning of replication studies. However, when these estimates are based on the original data used to detect the variant, the results are affected by an ascertainment bias known as the "winner's curse." The actual genetic effect is typically smaller than its estimate. This overestimation of the genetic effect may cause replication studies to fail because the necessary sample size is underestimated. Here, we present an approach that corrects for the ascertainment bias and generates an estimate of the frequency of a variant and its penetrance parameters. The method produces a point estimate and confidence region for the parameter estimates. We study the performance of this method using simulated data sets and show that it is possible to greatly reduce the bias in the parameter estimates, even when the original association study had low power. The uncertainty of the estimate decreases with increasing sample size, independent of the power of the original test for association. Finally, we show that application of the method to case-control data can improve the design of replication studies considerably.The American Journal of Human Genetics 05/2007; 80(4):605-15. · 10.60 Impact Factor