Showing papers by "Risto Sankila published in 2001"
TL;DR: Long-term survivors of childhood cancer had an increased mortality rate, mainly dying from primary cancers, however, modern treatments have reduced late cancer mortality without increasing the rate of therapy-related deaths.
Abstract: PURPOSE: To assess the risk of death in patients who survive more than 5 years after diagnosis of childhood cancer and to evaluate causes of death in fatal cases. PATIENTS AND METHODS: This was a population-based study in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) using data of the nationwide cancer registries and the cause-of-death registries. The study cohort included 13,711 patients who were diagnosed with cancer before the age of 20 years between 1960 and 1989 and who survived at least 5 years from diagnosis. By December 31, 1995, 1,422 patients had died, and death certificates were assessed in 1,402. Standardized mortality ratios (SMRs) for validated causes of death were calculated based on 156,046 patient-years at risk. RESULTS: The overall SMR was 10.8 (95% confidence interval [CI], 10.3 to 11.5), mainly due to high excess mortality from the primary cancer. SMR for second cancer was 4.9 (95% CI, 3.9 to 5.9) and was 3.1 (95% CI, 2.8 to 3.5) for noncancer death. The pat...
262 citations
TL;DR: The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.
Abstract: Background Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. Methods We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. Results Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. Conclusions We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.
227 citations
TL;DR: Assessment of the survival rates of familial breast cancer patients in Finland found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population.
Abstract: Reports on the prognosis of familial breast cancer patients have been contradictory. True differences in survival, if they exist, would have important implications for genetic counselling and in treatment of hereditary breast cancer. We assessed the survival rates of 359 familial breast cancer patients (32 patients from BRCA1-positive families, 43 patients from BRCA2-positive families and 284 patients from BRCA1/2-negative breast cancer families) and compared them with those of all other breast cancer patients diagnosed in Finland from 1953 to 1995 (n = 59,517). Cumulative relative survival rates (RSR) were calculated by dividing the observed survival rates by the expected ones. The expected survival rates were derived from the sex, age and calendar year specific life-tables of the general population in Finland. Regression model was used to calculate relative excess risk of death (RR) and to adjust for confounding factors. The overall 5-year RSR of the patients in the BRCA1 families, BRCA2 families, non-BRCA1/2 families and among sporadic cases was 67%, 77%, 86% and 78%, respectively. However, we found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population. In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63--2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39--1.57) than among the general breast cancer patient population. The RR among patients in the non-BRCA1/2 families did not differ from that of the general patient population.
71 citations
TL;DR: A population-based cohort study in the Nordic countries of 42277 siblings of 25605 children with cancer found no new patterns of familial cancer that indicated inherited susceptibility, or evidence that recessive conditions might contribute to cancers not explained by syndromes.
69 citations
TL;DR: The population-based study indicates that hereditary factors may play an important role in the development of prostate cancer among the relatives of men diagnosed both at younger and older ages.
Abstract: Objective: Five to ten percent of prostate cancers may be caused by inherited genetic defects In order to explore the nature of inherited cancer risks in the genetically homogeneous Finnish population, we investigated the incidence of prostate cancer and other cancers in first-degree relatives of prostate cancer patients by linking the population-based parish records on relatives with the Finnish Cancer Registry (FCR) data Methods: The study population was composed of first-degree relatives of two groups of prostate cancer patients diagnosed in Finland during 1988–1993: (1) all early-onset (≤60years) patients (n=557) from the entire country, (2) a sample (n=989) of prostate cancer patients diagnosed at an age of >60years A total of 11,427 first-degree relatives were identified through parish records, and their cancer incidence was determined based on a total of 299,970 person-years Standardized incidence ratios (SIR) were calculated based on expected cancer rates in the general population Results: The SIR of prostate cancer was increased in both Cohort 1 (25, 95% CI 19–32) and Cohort 2 (17, 95% CI 14–21) The risk of prostate cancer was high for relatives of patients diagnosed at an early age, and then leveled off for patients in the median age of prostate cancer diagnosis (70–79 years) However, the prostate cancer risk for relatives of patients diagnosed ≥80years was again statistically significantly elevated (SIR 18, 95% CI 13–26), suggesting a contribution of genetic factors to prostate cancer also at a late age of onset Gastric cancer was the only other cancer type with a significantly elevated risk among the relatives Increased risk of gastric cancer was seen only in male relatives of prostate cancer patients diagnosed at an early age, with the highest risk detected for the male relatives of prostate cancer patients diagnosed at an age of 55 years or less (SIR 50, 95% CI 28–82) Conclusions: Our population-based study indicates that hereditary factors may play an important role in the development of prostate cancer among the relatives of men diagnosed both at younger and older ages This finding is relevant in the context of our observations that HPCX (hereditary prostate cancer susceptibility locus on Xq27-28) linkage in Finland is found exclusively among families with late age of onset The association of gastric cancer with prostate cancer has not been reported previously, and may reflect the effects of a novel predisposition locus, which increases the risk to both of these common tumor types
56 citations
TL;DR: The excess risk of breast cancer in non-BRCA1/2 families suggests the existence of another predisposition gene which seems not to be linked with increased risk of ovarian cancer.
Abstract: Risk of cancer in BRCA1 and BRCA2 mutation-positive and -negative breast cancer families (Finland)
35 citations
TL;DR: Although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial gliomas patients suggests that the p53 gene is not a common susceptibility gene in case of familialgliomas.
Abstract: The high incidence of gliomas in Li–Fraumeni families and the high frequency of somatic p53 mutations in sporadic glial tumors have raised the possibility that germline p53 mutations could play an important role in familial aggregation of gliomas. In the present study, 18 families with two or more gliomas were screened for germline p53 mutation. The families were identified through questionnaires sent to 369 consecutive glioma patients operated at Tampere University Hospital during 1983–1994. In these families, a family history of cancer was verified through the Finnish Cancer Registry. Interestingly, the questionnaires revealed only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fulfilled the criteria for classic Li–Fraumeni syndrome. Immunostaining analysis of p53 protein accumulation suggested that alterations of the p53 gene are as common in familial as in sporadic gliomas. Sequencing analysis of exons 4–10 of the p53 gene revealed no germline mutations in any of the 18 families. Thus, although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial glioma patients suggests that the p53 gene is not a common susceptibility gene in case of familial gliomas. The p53 tumor suppressor gene seems to have a similar role in the tumorigenesis of most familial and sporadic gliomas.
31 citations
TL;DR: Overall 5‐year relative survival rates have increased dramatically over the 25‐year period in both genders and for cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore.
Abstract: The Singapore Cancer Registry has provided comprehensive population-based incidence data since 1968. This paper describes the population-based survival analysis of the registry data. All invasive primary cancers diagnosed from January 1, 1968 to December 31, 1992 were passively followed up until December 31, 1997. Only 5.8% were lost to follow-up. Cumulative and observed survival rates were calculated using Hakulinen's method. Overall 5-year relative survival rates have increased dramatically over the 25-year period in both genders. Significant increases are seen with nasopharynx, stomach and colo-rectum cancers, non-Hodgkin's lymphoma, leukemias and cancers of the testis, cervix, ovaries and breast. When compared with the Surveillance, Epidemiology and End Results (SEER) rates in the United States, the 5-year relative survival rates in Singapore are generally lower. However, the rate of change between the two countries is fairly similar. On the average, the rates are 10 to 15 years behind the SEER rates and 5 to 10 years behind Finland, Switzerland and Japan, but they are close to the UK rates. The age-standardized 5-year survival rate for Singapore is higher for most sites compared with other developing countries like Qidong (China), Madras (India), Bombay (India) and Chiang Mai (Thailand). The 25-year trend in cancer survival in Singapore showed two extreme groups: those showing no change and those showing significant improvements. Reducing the incidence of cancers belonging to the first group remains the only viable mode of cancer control. For cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore.
31 citations