BACKGROUND: A positive family history is one of the strongest known risk factors for prostate carcinoma in addition to age and race. In this article, the authors present age specific risks for developing prostate carcinoma in families with an aggregation of prostate carcinoma. METHODS: Data from a population-based cohort study including 5706 sons of Swedish men who had been diagnosed with prostate carcinoma between 1959 and 1963 were used. The age specific incidence rates were calculated for different cohorts of prostate carcinoma families with respect to patient age at the time of prostate carcinoma diagnosis and the number of men affected. RESULTS: Both patient age at the time of prostate carcinoma diagnosis and the number of men affected in the families influenced the risk of developing prostate carcinoma significantly. Unaffected men in families with two or more cases of prostate carcinoma have a very high risk of developing prostate carcinoma at a young age. The cumulative risks in these families are 5%, 15%, and 30% by ages 60 years, 70 years, and 80 years, respectively, compared with only 0.45%, 3%, and 10%, respectively, at the same ages in the general population. CONCLUSIONS: The findings of the current study together with data from the literature support the case for the screening of high risk families. The authors also conclude that men with at least two close relatives with prostate carcinoma have a very high risk of developing prostate carcinoma before age 70 years. The authors recommend these men undergo testing for prostate specific antigen and a digital rectal examination annually between the ages 50 years 70 years, ages at which patients usually are offered curative treatment for localized tumors. Screening of individuals before age 50 years may be recommended in selected families with a history of prostate carcinoma of very early onset.
BACKGROUND: Little is known regarding the clinical features of hereditary prostate carcinoma (HPC) and whether other malignancies are associated with this disease. The aim of this study was to investigate whether tumors other than prostate carcinoma aggregate in families with HPC or whether this disease can be considered site specific. METHODS: From 62 Swedish families with HPC, a cohort was constructed of 1364 first-degree relatives of the men with prostate carcinoma in these families. Through linkage to the Swedish Cancer Register, all reported cancer between 1958 and 1996 was identified. The expected number of cases was calculated by using the population rates in Sweden. RESULTS: A standardized incidence ratio (SIR) of 1. 16 (95% confidence interval [95% CI], 0.97-1.38) for the overall cancer risk was observed among the 1364 first-degree relatives. However, significant increased risks were noticed for gastric carcinoma (SIR, 2.78; 95% CI, 1.59-4.52), for breast carcinoma in women (SIR, 1.58; 95% CI, 1.01-2.35), and for kidney carcinoma (SIR, 2.51; 95% CI, 1.15-4.77).The excess risk for breast carcinoma was even more pronounced among women before the age of 65 years in families with earlier onset prostate carcinoma (SIR, 3.64; 95% CI, 1. 66-6.91). Seven families with at least two or more relatives with breast, gastric, or kidney carcinoma were identified, and, in one family, four relatives with early onset gastric carcinoma were observed. CONCLUSIONS: In most of the families with HPC, the disease appears to be "site specific," with no excess of other malignancies. However, in a subset of families, a significant aggregation of prostate carcinoma together with breast carcinoma and/or gastric carcinoma was observed that may have been caused by a common germline mutation in a cancer susceptibility gene.
Many cancer patients receive chemotherapy and radiotherapy their last 30 days [end of life (EOL)]. The benefit is questionable and side effects are common. The aim of this study was to investigate what characterized the patients who received chemo- and radiotherapy during EOL, knowledge that might be used to improve practice.
Patients dead from cancer in 2005 and 2009 were analyzed. Data were collected from hospital medical records. When performance status (PS) was not stated, PS was estimated from other information in the records. A Glasgow Prognostic Score (GPS) of 0, 1 or 2 was assessed from blood values (CRP and albumin). A higher score is associated with a shorter prognosis.
In total 616 patients died in 2005; 599 in 2009. Among the 723 analyzed, median age was 71; 42% had metastases at diagnosis (synchronous metastases); 53% had PS 2 and 16% PS 3-4 at the start of last cancer therapy. GPS at the start of last cancer therapy was assessable in 70%; of these, 26% had GPS 1 and 35% GPS 2. Overall, 10% received chemotherapy and 8% radiotherapy during EOL. The proportions varied significantly between the different types of cancer. Multivariate analyses revealed that those at age
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited syndrome which confers an increased risk for colorectal cancer and endometrial cancer as well as other tumors. It is caused by germline DNA mismatch repair (MMR) gene mutations in five MMR genes, hMSH2, hMLH1, hPMS1, hPMS2 and hMSH6. Finding mutations in these high risk families means that you can offer presymptomatic carrier diagnosis and thereby identify individuals with a very high risk for cancer. These persons benefit from counseling and should be offered surveillance. We have used DGGE to screen members from 34 families for mutations in hMLH1 and hMSH2. Six mutations in five families were found, five of these mutations are new. Besides, three new polymorphisms were identified. The mutations were found in two of seven Amsterdam criteria HNPCC families and in three of four families with at least one case of early onset of CRC (before 35), suggesting there are appropriate families to be chosen for mutation screening in MMR genes.
BACKGROUND: In a European setting, we know little about the use of dietary supplements among men with prostate cancer (PCa) and to what extent lifestyle, disease or other factors influence such use. PATIENTS AND METHODS: We evaluated supplement use in 1127 men with incident PCa and in 900 population controls in Sweden. Age-adjusted binary regression with an identity link was carried out to estimate prevalence differences and corresponding 95% confidence intervals (CIs). Modifying effects of lifestyle- and diet-related factors were explored by statistical assessment of additive interaction. RESULTS: Among men with PCa, 542 individuals (48%) had used supplements, which was a 10% (95% CI: 5.9%-15%) higher prevalence than among population controls. Among individuals with high intake of fatty fish, vegetables, and phytoestrogens, but low intake of saturated fat, supplement use was 29% (95% CI: 18%-41%) more common in men with PCa than in population controls. We found no evidence of heterogeneity by categories of education, smoking history, body mass index, fiber, fruit, or phytoestrogen intake, treatment, or disease stage. CONCLUSION: Supplement use is common in Swedish men with PCa, especially among those with a healthy dietary pattern.
In a recent study of 91 families having at least three first degree relatives with prostate cancer, we reported the localization of a major susceptibility locus for prostate cancer (HPC1) to chromosome 1 [band q24; J. R. Smith et al., Science (Washington DC), 274: 1371-1373, 1996]. There was significant evidence for locus heterogeneity, with an estimate of 34% of the families being linked to this locus. In this report, we investigate the importance of age at diagnosis of prostate cancer and number of affected individuals within a family as variables in the linkage analysis of an expanded set of markers on 1q24. Under two different models for the prostate cancer locus, we find that the evidence for linkage to HPC1 is provided primarily by large (five or more members affected) families with an early average age at diagnosis. Specifically, for 40 North American families with an average age at diagnosis
Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.
This population-based cohort study investigated the occurrence of familial astrocytoma among first-degree relatives of patients with astrocytoma diagnosed between 1985 and 1993 in the northern region of Sweden. The 432 cases received a questionnaire. They were asked to provide names and cancer diagnoses of first-degree relatives. Of the 297 answering, a cohort was constructed of their 1,890 first-degree relatives (FDR). A significantly increased risk [standardized incidence ratio, SIR = 2.12, 95% confidence interval (CI) = 1.18-3.49] was shown for developing primary brain tumors (PBT). In 4.7% (14/297) of the families, a PBT was found. Interestingly, the increased risk was for astrocytoma only (SIR = 3.12, 95% CI 1.42-5.92), and not for other PBT (SIR 0.90, 95% CI 0.18-2.64). When the cohort was divided according to the median age of proband, most of the increased risk was restricted to the younger cohort (SIR = 4.71, 95% CI 1.52-10.99). Surprisingly, a significantly decreased risk for breast cancer and colon cancer was shown. The finding that the increased risk is restricted to astrocytoma only is a novel one. This study implies that familial aggregation of astrocytoma exists; the familial clustering occurs in a small fraction of astrocytoma, and might be explained by inherited factors.
There is a familial aggregation of prostate cancer, and 5 to 10% of all prostate cancers are estimated to be inherited in an autosomal-dominant mode. A population-based cohort study was performed in order to study familial prostate cancer and associated malignancies. A nation-wide register cohort study was conducted using an unselected study population. The cohort of 5,595 sons and 5,089 daughters of Swedish men found to have prostate cancer between 1959 and 1963 was identified. All types of cancer reported between 1958 and 1992 in this cohort were identified through linkage to the Swedish Cancer Registry. The expected number of different cancers was calculated using incidence rates obtained from the Registry. A highly significant increased overall standardized incidence ratio (SIR) of 1.65 (95% CI, 1.49-1.83) was obtained for prostate cancer, with 370 observed cases compared with 224 expected prostate cancers. The SIR was 3.18 among cases 45 to 49 years old at diagnosis, with the risk gradually decreasing to a SIR of 1.45 among cases over 80 years of age. Among sons and daughters with a father whose prostate cancer was diagnosed at an early age (
BACKGROUND. Although prostate carcinoma is not widely recognized as a familial cancer, familial aggregation of this disease has been shown in some retrospective case-control studies. To study familial prostate cancer in Sweden, a population-based cohort study was performed, that attempted to avoid possible bias connected with some earlier studies of familial prostate cancer. METHODS. A nationwide register cohort study was conducted using an unselected study population. The study cohort of 5496 sons of Swedish men found to have prostate cancer between 1959 and 1963 was identified through parish offices. All prostate cancer patients reported between 1958 and 1990 in this cohort were identified through linkage to the Swedish Cancer Register. The expected number of prostate cancer patients was calculated using incidence rates obtained from the same register. RESULTS. A highly significant increased overall standardized incidence ratio (SIR) of 1.70 (95% confidence interval, 1.51-1.90) was obtained for prostate cancer in this cohort, with 302 observed cases compared with 178 expected prostate cancers. The SIR was 3.38 among patients aged 45-49 years at diagnosis, with the risk gradually decreasing to a SIR of 1.35 among patients older than 80 years (trend, P = 0.013). Among sons with a father whose prostate cancer was diagnosed at an early age (