No abstract

Individuals with a family history of CRC and CRA have a significantly elevated risk of developing CRC compared with those without such a history. Risks are greatest for relatives of patients diagnosed young, those with two or more affected relatives, and relatives of patients with colonic cancers.

calculating the weighted average of the log relative risk (RR) estimates from studies. RESULTSThe pooled RR (95% confidence interval) in first-degree relatives was 2.5 (2.2-2.8). There was evidence that this was highest in relatives of cases diagnosed before age 60 years and that RRs declined with age. The risk for the few men with two affected relatives was increased 3.5-fold (2.6-4.8). RRs to sons of cases appeared to be lower than in brothers; a complete explanation of this observation is uncertain. CONCLUSIONMen with a family history of prostate cancer have a significantly greater risk of developing prostate cancer than those with no such history. Risks are greatest for relatives of cases diagnosed when young and those with more than one relative affected. KEYWORDSprostate cancer, familial risk, meta-analysis OBJECTIVETo identify published studies quantifying familial prostate cancer risks in relatives of prostate cancer cases and, by meta-analysis, obtain more precise estimates of familial risk according to the family history.

OBJECTIVE To assess the rate of prostate‐specific antigen (PSA) testing for prostate cancer in general practice in asymptomatic and symptomatic patients. SUBJECTS AND METHODS The cross‐sectional study took place in England and Wales, was population‐based and covered 469 159 men aged 45–84 years. Pathology data on PSA tests requested between 19 November 1999 and 31 May 2002 by general practitioners (GPs) were provided by 28 pathology laboratories. The practices recorded reasons for the tests between 1 December 2001 and 31 May 2002. In all, 391 practices in which all GP partners participated were included in the analyses. RESULTS The overall annual rate of testing in men with no previous diagnosis of prostate cancer was estimated to be 6%, of which the annual rates of asymptomatic, symptomatic and re‐testing were 2.0%, 2.8% and 1.2%, respectively, after adjusting for missing values. The rate decreased with increasing social deprivation, and with increasing proportions of black and Asian populations. The overall rate of PSA testing increased significantly from 1999 to 2002. CONCLUSIONS If the recommendations of the National Health Service Prostate Cancer Risk Management Programme were applied, 14% of asymptomatic tests and 23% of symptomatic tests would have led to a referral. As the rate of PSA testing is increasing and there are uncertainties about the benefit of screening, the workload and costs in general practice and hospitals should be monitored.

Purpose: There is a paucity of data quantifying the familial risk of colorectal cancer associated with mismatch repair (MMR)-deficient and MMR-stable tumors. To address this, we analyzed a population-based series of 1,042 colorectal cancer probands with verified family histories. Experimental Design: Constitutional DNA from probands was systematically screened for MYH variants and those with cancers displaying microsatellite instability (MSI) for germ-line MMR mutations; diagnoses of familial adenomatous polyposis and juvenile polyposis were established based on clinical phenotype and mutational analysis. Familial colorectal cancer risks were enumerated from age-, sex-, and calendar-specific population incidence rates. Segregation analysis was conducted to derive a model of the residual familial aggregation of colorectal cancer. Results: Germ-line predisposition to colorectal cancer was identified in 37 probands [3.4%; 95% confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic MYH variants. The risk of colorectal cancer in first-degree relatives of probands with MSI and MMR-stable cancers was increased 5.01-fold (95% CI, 3.73-6.59) and 1.31-fold (95% CI, 1.07-1.59), respectively. MSH2/ MLH1 mutations were responsible for 50% of the overall excess familial risk and 80% of the risk associated with MSI cancers but 32% of the familial risk was unaccounted for by known loci. Genetic models based on major gene loci did not provide a better explanation of the residual familial aggregation than a simple polygenic model. Conclusions:The information from our analyses should be useful in quantifying familial risks in clinical practice and in the design of studies to identify novel disease alleles.Family history is acknowledged to be one of the strongest risk factors for the development of colorectal cancer. Numerous studies have documented that f15% of individuals with colorectal cancer report a close relative also affected by the disease (1 -3). A meta-analysis of epidemiologic studies we conducted showed that having a first-degree relative with colorectal cancer approximately doubled the risk of colorectal cancer, and if the affected relative was diagnosed before the age of 45 years, the risk was increased f4-fold (4).Germ-line mutations in APC, SMAD4, ALK3, STK11/LKB1, MYH, and the mismatch repair (MMR) genes have all been shown to be predispose to syndromic forms of colorectal cancer: familial adenomatous polyposis (FAP; Mendelian inheritance in man 175100), 5 juvenile polyposis (Mendelian inheritance in man 174900), Peutz-Jeghers syndromes (Mendelian inheritance in man 175200), recessive polyposis (MYH; Mendelian inheritance in man 608456), and hereditary nonpolyposis colorectal cancer (HNPCC; Mendelian inheritance in man 120435-6), respectively (5). Aside from the substantive risk associated with HNPCC (6, 7), germ-line mutations in the MMR genes are thought to contribute significantly to the overall burden o...