Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.

Recently, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in a number of developed (Western) countries. However, risk factors in these low-risk populations are poorly understood. In this nationwide population based case-control study in Denmark, we examined the relationship between selected medical conditions and subsequent ICC risk to provide additional clues to etiopathogenesis. All histologically confirmed ICC cases diagnosed in Denmark between 1978 and 1991 were identified from the Danish cancer registry. Population controls were selected from the central population registry and were matched 4:1 to cases on sex and year of birth. Cases and controls were linked to the Danish hospital discharge registry to obtain information on prior hospital diagnoses. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived using conditional logistic regression. A total of 764 ICC cases and 3,056 population controls were included in the study. Chronic liver diseases were significantly related to ICC: alcoholic liver disease (OR 5 19.22, 95% CI 5 5.55-66.54), unspecified cirrhosis (OR 5 75.9, 95% CI 10.2-565.7). Bile duct diseases were also associated with risk: cholangitis (OR 5 6.3, 95% CI 5 2.3-17.5), choledocholithiasis (OR 5 23.97, 95% CI 5 2.9-198.9), cholecystolithiasis (OR 5 4.0, 95% CI 5 2.0-7.99), though gallbladder removal did not change risk (OR 5 1.6, 95% CI 5 0.65-3.7). Among other conditions, chronic inflammatory bowel disease (OR 5 4.7, 95% CI 5 1.65-13.9) was significantly associated with ICC. Diabetes was associated with risk in the year prior to diagnosis of ICC (OR 5 3.02, 95% CI 5 1.05-8.69). Obesity was unrelated to risk. These results confirm that prior bile duct diseases increase risk of ICC and suggest that alcoholic liver disease and diabetes may also increase risk. ' 2006 Wiley-Liss, Inc.Key words: intrahepatic cholangiocarcinoma; risk factors; populationbased case control study Intrahepatic cholangiocarcinoma (ICC), the second most common form of primary liver cancer (after hepatocellular carcinoma) in the world, is characterized by wide variability in incidence and risk factors.1 In high-risk areas, such as Northeast Thailand, the primary risk factor for ICC is infestation with liver flukes (Ophistorchis viverrini, Clonorchis sinensis and hepatolithiasis).2-4 In low-risk areas, such as Europe and North America, ICC incidence has been increasing in recent decades 5,6 and the etiology is poorly understood as the conduct of epidemiological studies is complicated by the rarity of the tumors. In these areas, primary sclerosing cholangitis and inflammatory bowel diseases are the most commonly reported risk factors for ICC.7-10 It is unclear whether the incidence of these conditions has changed, however, and, as these conditions are generally more common among younger persons with ICC, 10 they are unlikely to account for increasing ICC risk in the elderly population. Additionally, alcoholic liver disease, cirrhosis, hepatitis C virus, human immunodeficiency virus an...

OBJECTIVEAmong adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity.RESEARCH DESIGN AND METHODSA cohort of 699 adolescents, 10–17 years of age, <2 years duration of type 2 diabetes, BMI ≥85%, HbA1c ≤8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg.RESULTSIn this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria.CONCLUSIONSPrevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.

OBJECTIVES-Our goal was to report the prevalence of elevated blood pressure and lipid levels among eighth-grade adolescents from 3 US locations and differences by gender, ethnicity, and overweight percentile group.METHODS-Fasting blood samples and blood pressure levels were obtained from 1717 eighthgrade students from 12 predominantly minority schools in 3 states (Texas, California, and North Carolina) during spring 2003. Age, gender, ethnicity, weight, and height were ascertained and BMI calculated. The presence of abnormal total cholesterol, high-density lipoprotein cholesterol, lowdensity lipoprotein cholesterol and triglycerides, prehypertension, hypertension, at risk for overweight, and overweight were calculated and compared with the findings of previous youth studies. We examined whether prevalence differed by gender, ethnicity, or BMI group.RESULTS-A total of 23.9% of participants had high blood pressure, 16.7% had borderline total cholesterol, 4.0% had high total cholesterol, 10.5% had borderline low-density lipoprotein cholesterol, 3.9% had high low-density lipoprotein cholesterol, 13.3% had low high-density lipoprotein cholesterol, and 17.2% had high triglycerides. A total of 19.8% of participants were at risk of overweight (BMI ≥85th percentile, <95th percentile) and 29% were overweight (BMI ≥95th percentile). The prevalence of risk factors was associated (P < .05) with the overweight group and differed by age and gender.CONCLUSIONS-Prevalence of elevated blood pressure was higher in this sample than in previous national surveys in which subjects were less overweight. Associations between overweight and both elevated lipid and blood pressure levels suggest that adolescents overweight or at risk for overweight should be screened for elevated blood pressure and lipid levels. Address correspondence to Russell Jago, PhD, Department of Exercise and Health Sciences, University of Bristol, Centre for Sport Exercise and Health, Tyndall Avenue, Bristol BS8 1TP, United Kingdom. E-mail: E-mail: russ.jago@gmail.com. The authors have indicated they have no financial relationships relevant to this article to disclose. [3][4][5][6] suggesting that the presence of elevated lipid or cholesterol levels during adolescence increases the risk of adult disease. Lipid levels and blood pressure levels have also been reported to vary by ethnicity, 7-10 gender, 7,9 and Tanner stage 11,12 among children and adolescents. NIH Public AccessIn the Bogalusa Heart Study (1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994), 11.4% of 11-to 17-year-olds were overweight (Quetelet index), 9% had high total cholesterol (TC) levels (>200 mg/dL), 8% had high (>130 mg/dL) low-density lipoprotein cholesterol (LDL-C), and 11% had low (<35 mg/dL) highdensity lipoprotein cholesterol (HDL-C). 13 Recent data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 showed that the prevalence of high triglycerides and low HDL-C remained virtually unchanged since NHANES III (1998III ( -1994 among 12-to 19-ye...