International variation in pancreatic cancer mortality for the period 1955-1998.

BACKGROUND: Pancreatic cancer is an important cause of cancer mortality in developed countries. This article examines time trends for pancreatic cancer mortality rates in 38 countries on five continents between 1955 and 1998. METHODS: We used the World Health Organization database on Age-Standardized World Population pancreatic cancer mortality rates by gender and fitted these data with linear regression models. This allowed us to (1) investigate the statistical significance of temporal trends; and (2) consider differences in trends among countries; and (3) predict future pancreatic cancer mortality rates. RESULTS: Over 44 years, pancreatic cancer mortality rates increased for females worldwide. Pancreatic cancer mortality rates for men increased in Southern Europe. In contrast, pancreatic cancer mortality rates for men in North America and Oceania increased until about 1975 and then decreased or remained stable. Our predictive models suggest that by 2005 the relative burden of pancreatic cancer mortality will have shifted away from Northern Europe and North America toward Southern Europe and Asia. CONCLUSIONS: Future research on pancreatic cancer should concentrate separately on the assessment of risk attributable to exposure to environmental factors, lifestyle factors, genetic determinates of pancreatic cancer, and the interactive influences of these factors on pancreatic cancer.

Genetic and environmental contributions to platelet aggregation: the Framingham heart study.

BACKGROUND: Platelet aggregation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease. However, the contribution of genetic versus environmental influences on interindividual variation in platelet aggregability is poorly characterized. METHODS AND RESULTS: We studied the heritability of platelet aggregation responses in 2413 participants in the Framingham Heart Study. The threshold concentrations of epinephrine and ADP required to produce biphasic platelet aggregation and collagen lag time were determined. Mixed-model linear regression was used to calculate correlation coefficients within sibships and within spouse pairs. Variance and covariance component methods were used to estimate the proportion of platelet aggregation attributable to measured covariates versus additive genetic effects. After accounting for environmental covariates, the adjusted sibling correlations for epinephrine, ADP, and collagen lag time were 0.24, 0.22, and 0.31, respectively (P=0.0001 for each). In contrast, adjusted correlations for spouse-pairs were -0.01, 0.05, and -0.02, respectively (all P>0.30). The estimated heritabilities were 0.48, 0.44, and 0.62, respectively. Measured covariates accounted for only 4% to 7% of the overall variance in platelet aggregation, and heritable factors accounted for 20% to 30%. The platelet glycoprotein IIIa Pl(A2) polymorphism and the fibrinogen Hind III beta-148 polymorphism contributed <1% to the overall variance. CONCLUSIONS: In our large, population-based sample, heritable factors play a major role in determining platelet aggregation, and measured covariates play a lesser role. Future studies are warranted to identify the key genetic variants that regulate platelet function and to lay the groundwork for rational pharmacogenetic approaches.