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STUDY QUESTION What is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women? SUMMARY ANSWER The incidence of POI increased among females aged 15–19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased. WHAT IS KNOWN ALREADY So far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause. STUDY DESIGN, SIZE, DURATION Population-based study with 5011 women diagnosed with POI in 1988–2017. The data were collected from national registries and covers POI subjects in entire Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model. MAIN RESULTS AND THE ROLE OF CHANCE The incidence was highest in the 35–39 age group, ranging from 73.8/100 000 women-years in 1993–1997 to 39.9/100 000 women-years in 2013–2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015–2017. Cumulative incidence of POI for women under 40 years in 1988–2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3–6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls. LIMITATIONS, REASONS FOR CAUTION For some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria. WIDER IMPLICATIONS OF THE FINDINGS The risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

Breast cancer (BC) and diabetes mellitus (DM) are major health problems. We examined the association between DM and BC stage at diagnosis and subsequent survival in a Finnish cohort of female BC patients. All BC cases (N = 73,170) diagnosed in 1995-2013 with dates and causes of death were identified from the Finnish Cancer Registry. Participation in organized mammography screening was obtained from Mass Inspection Registry. Information on DM diagnoses and background conditions recorded during 1995-2013 were obtained from national Care Register for Health Care and merged to data on medication use from the national Prescription Register. Logistic regression with adjustment for mammography screening and age at BC diagnosis was used to evaluate the risk of advanced stage BC at diagnosis. Cox regression was used to evaluate overall and BC survival. Analyses were adjusted for age, background conditions and mammography screening. Survival analyses were further adjusted for tumor extent, histology and primary treatment. Of the cohort 11,676 (16.0%) had DM. Screening participation did not differ by diabetes. Compared to non-diabetic women, diabetics had more often locally advanced (odds ratio, OR 1.26; 95% CI 1.18-1.35) or metastatic BC (OR 1.59; 95% CI 1.44-1.75) at diagnosis. During a median follow-up of 5.8 years after BC diagnosis 10,900 (14.9%) women died of BC. Risk of BC death was higher among diabetic compared to non-diabetic women (HR 1.36; 95% CI 1.27-1.46). Risk of BC death increased with duration of DM. This supports DM as a risk factor for fatal BC.

The objective of this study was to determine the site-specific cancer incidence of hypertensive patients and examine the effect of blood pressure-related variables on the risk of cancers with elevated incidence among the hypertensive patients. A record linkage study of Hypertension Register of the North Karelia Project and the Finnish Cancer Registry was conducted. The mean follow-up time was 16 years. A total of 20 529 hypertensive patients were studied. Main outcome measures were standardised incidence ratios and hazard ratios. The overall cancer incidence was close to that of the general population for both men and women. The incidence rate for the kidney cancer was significantly increased in hypertensive patients (standardised incidence ratio 1.34, 95% confidence interval (CI) 1.11-1.60), as well as incidence rates for cancers of pancreas (1.26, 1.02-1.54), and endometrium (1.22, 1.01-1.44) in hypertensive women. The incidence of lung cancer was significantly decreased (0.86, 0.77-0.95). The incidence of liver cancer was elevated with borderline significance (1.36, 0.99-1.82). In Cox regression models, the use of antihypertensive drugs at baseline was a significant predictor of kidney (hazard ratio for use of antihypertensive drugs 1.89, 95% CI 0.96-3.75) and pancreatic cancer (1.78, 0.99-3.22) in women but not in men. The incidence of endometrial cancer or liver cancer was not related to blood pressure levels or the use of antihypertensive drugs. In women, obesity was a significant predictor of cancers of the endometrium, kidney and liver. In conclusion, increased occurrence of some cancer types among hypertensive patients seem to be partly explained by obesity and the use of antihypertensive drugs.

A study on cancer incidence after kidney transplantation was performed using data of national transplant and cancer registries. Since 1964 up to 30 June 1997, 3440 kidney transplantations were performed on 2890 patients. From 1967 to 1997, 230 posttransplantation malignancies were found in 20 817 patient-years of follow up. The standardised incidence ratio (SIR) was 3.33 compared to the general population. The SIR was highest in skin cancer (39.2). The SIRs were high in cancers of the lip (23.0), thyroid (8.08), kidney (8.0), lower urinary tract (3.2), non-Hodgkin lymphoma (4.8), ovary (3.9) and colon (3.9). Skin cancer and lymphomas had much higher SIRs in men than in women whereas lower urinary tract cancer had a higher SIR in women. During the first 10 follow up years, life-table analysis indicates a higher cancer risk in cyclosporine-treated patients, but this may be biased by their shorter follow up as the overall SIR was equal in both groups. This population study shows the increased incidence of cancer in the transplant population and points out the importance of cancer surveillance in the years following kidney transplantation.

The purpose of the study was to estimate subsequent incidence of cervical cancer among women with positive cytology followed by negative histology.This was a longitudinal cohort study involving about 80,000 women with class II, III, IV or V cytology at the organized mass screening in Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from the fifth month following the initial screening and ended on December 31, 1995.Standardized incidence ratios (SIR) of invasive cervical cancer varied from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from 3.0 (class II) to 20 (class V) compared to the risk among the total Finnish female population of same age and calendar period. The relative risk was greatest during first years of follow-up for both preinvasive and invasive cervical lesions, and it remained significantly high over 5 years of follow-up. For women with class II cytology there were peaks in relative risk in the years of subsequent rescreenings.Women with positive cytology have a high relative risk of cervical cancer even when excluding the cancers found at screening; the high relative risk is persistent for more than 5 years, and therefore these women should be kept under close surveillance and repeated smears should be taken with relatively short intervals.

The purpose of our study was to find out whether bleeding symptoms are predictive factors of subsequent gynecological or urinary cancers among women screened negative.The data stemmed from the Finnish Mass Screening Registry, and were linked to the National Cancer Registry: 37,596 screening negative women in the nationwide population-based mass screening program for cervical cancer were classified by their bleeding symptom (bloody discharge, coital bleeding, irregular bleeding, postmenopausal bleeding) at the time of screening (1985-1990) and followed up (1985-1994) in order to assess the subsequent risk of cancer.Bleeding symptoms with prevalence of 5.9% were more likely to be signs of preinvasive than invasive cervical cancer with the exception of coital bleeding, nevertheless relative risk of cervical cancer (SIR 1.1, 95% CI 0.8-1.4) was not significantly increased during the total follow-up of maximum 10 years. Women with any bleeding symptom had increased risk of cancer of the corpus uteri (SIR 2.1, 95% CI 1.6-2.6), postmenopausal bleeding was the strongest symptom (RR 3.6, 95% CI 2.0-6.0). None of the bleeding symptoms increased subsequent risk of ovarian, vaginal or vulvar carcinoma. The risk of kidney cancer was increased (SIR 1.7, 95% CI 1.0-2.6).The prevalence of bleeding symptoms was small and relative risks for cancers were low for them to be suitable as predictive factors of cancer neither in clinical practice nor for public health purposes, e.g. in developing selective screening based on this high risk group. Only 34 gynecological cancers during 220,000 person-years in women with bleeding symptoms were attributable to bleeding. Relative risks remained increased only for a short time after screening. Therefore, short term surveillance is important, but due to the fact that relative risks approached unity during the follow-up, reassurance of a woman that she is cancer-free should be emphasized more in the long term after the bleeding symptoms.

The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.

To study the long term risk of cancer in patients with rheumatoid arthritis (RA) who have been treated with yttrium.The medical record numbers of 1228 patients with RA who were admitted to hospital in 1979-85 were identified in the database of Jyväskylä Central Hospital. Radiosynovectomy of the knee joint was performed in a total of 143 patients using yttrium-90 silicate during the years 1970-85, while 1075 did not receive yttrium radiosynovectomy; 10 received yttrium treatment later than 1985 and were excluded from the analysis. The Finnish Cancer Registry database was used to examine whether the subjects had cancer during the follow up from 1979 until the end of 1999.Nine cases of cancer were found among the patients who had received yttrium, whereas the expected number based on the incidence among the population in the region was 14.9. The standardised incidence ratio of cancer was 0.6 (95% confidence interval (CI) 0.3 to 1.1) for the patients who received yttrium, and 1.1 (95% CI 0.9 to 1.3) for the patients who did not receive yttrium.Yttrium treatment did not increase the risk of cancer.

The risk of smoking-related secondary cancers developing in bladder cancer patients was studied. The study population consisted of 10,014 bladder cancer patients reported to the Finnish Cancer Registry between 1953 and 1989. The risk of contracting a new primary cancer was estimated as a standardized incidence ratio, defined as the ratio of the observed and expected numbers of cases. Of 660 secondary cancers (6.6%) observed (standardized incidence ratio 0.96) 44% were considered to be smoking-related. Lung cancer was the most common secondary cancer (30% overall), and it occurred significantly more often than expected (standardized incidence ratio 1.31, 95% confidence interval 1.13 to 1.50). Also, larynx cancer among men (standardized incidence ratio 1.67, 95% confidence interval 0.95 to 2.79) and kidney cancer among women (standardized incidence ratio 3.55, 95% confidence interval 1.84 to 6.20) were found more often than expected. These excess risks were observed up to 20 years after diagnosis of bladder cancer. Therefore, bladder cancer patients experience an excess risk of smoking-related new tumors, which must be acknowledged during the initial evaluation and regular followup of such patients.

Cancers of the mandibular region show the lowest survival rates of all oral cancers. In order to compare the effect of five different modes of treatment (including surgery and/or radiotherapy), a series of 159 patients was analysed. When adjustments were made for age, sex and tumour stage in a log-linear multivariate analysis, no differences between treatments in the 5-year relative survival rates (RSR) could be demonstrated for stage I and II tumours. In stage III and IV tumours, radiation treatment alone resulted in poor survival. Between the other four treatments, all including surgery, no statistically significant differences in the 5-year relative survival rates were found. Radiation therapy as an element in combination therapy may have postponed a recurrence but did not affect the 5-year survival rate. For advanced tumours, mostly responsible for the low overall 5-year RSR, higher survival rates can possibly be achieved by improving surgical treatment of the primary lesion and the neck. At present, however, only earlier diagnosis might significantly increase the survival rates.

The relationship between dietary fat and subsequent risk of breast cancer was studied in 3988 initially cancer-free Finnish women aged 20-69 y. During a follow-up period of 20 y, 54 breast-cancer cases were diagnosed. Risk of breast cancer was significantly inversely related to energy intake and nonsignificantly inversely related to absolute fat intake. A positive association between energy-adjusted total fat intake and occurrence of breast cancer was also observed. The relative risk in the highest tertile as compared with the lowest tertile was 1.7 (95% confidence limits 0.6-4.8). The corresponding relative risks were 1.4 (0.5-3.7) for saturated fatty acids, 2.7 (1.0-7.4) for monounsaturated fatty acids, 1.2 (0.6-2.8) for polyunsaturated fatty acids, and 2.2 (1.0-5.0) for cholesterol intake. Adjustment for different potential confounding factors did not alter the results. The present data suggest that breast cancer is associated inversely with energy intake and weakly positively with energy-adjusted fat intake.

Broad variations in the incidence of gestational trophoblastic diseases have been reported in different parts of the world. Recent time trends in the incidence of hydatidiform mole in Western countries have not been elucidated. We studied the epidemiology of hydatidiform mole in Finland over a period of 27 years.Women reported to have hydatidiform mole from 1975-2001 were identified from the National Research and Development Center for Welfare and Health. Women with choriocarcinoma were identified from the Finnish Cancer Registry.We identified 1659 cases of hydatidiform mole between 1975 and 2001. This gives an incidence of 73/10(6) women or 984/10(6) deliveries. The overall incidence remained fairly constant over the study period. The incidence was higher in women below 20 years and above 39 years than in women in the other age groups. Forty-nine percent of choriocarcinomas identified during the study period were associated with a preceding hydatidiform mole. The risk of choriocarcinoma after a hydatidiform mole was 2.2%.The incidence of hydatidiform mole in Finland follows the same patterns as in other Western countries. The incidence has not changed considerably in recent decades.

To compare the risk of cancer between BRCA1 or BRCA2 mutation-positive and -negative families.We assessed standardized incidence ratios (SIR) in 107 Finnish breast cancer families (12 BRCA1, 11 BRCA2, 84 non-BRCA1/2) with confirmed genealogy. The observed numbers of cancer cases were compared to the expected ones; both numbers were based on the population-based Finnish Cancer Registry.Risk of ovarian cancer for first-degree relatives was high in BRCA1 (SIR 29, 95% confidence interval 9.4-68) and in BRCA2 families (SIR 18. 8.3-35), but not increased for non-BRCA1/2 families (SIR 1.0, 0.2-2.9). The SIR for subsequent ovarian cancer among breast cancer patients was 61 (20-142), 38 (11-98), and 0 (0-4.2), respectively. The risk of subsequent new breast cancer among breast cancer patients was equally high in BRCA1 families (SIR 11, 3.6-26) and in BRCA2 families (SIR 10, 3.3-24) and somewhat lower in mutation-negative families (SIR 3.7, 2.1-6.1). The risk of breast cancer among relatives was markedly increased in all three groups. The only elevated SIR, besides breast and ovarian, was that for prostate cancer in BRCA2 families (SIR 4.9, 1.8-11).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.

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.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 (60 years) patients (n = 557) from the entire country, (2) a sample (n = 989) of prostate cancer patients diagnosed at an age of60 years. 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.The SIR of prostate cancer was increased in both Cohort 1 (2.5, 95% CI 1.9-3.2) and Cohort 2 (1.7, 95% CI 1.4 2.1). 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 diagnosedor = 80 years was again statistically significantly elevated (SIR 1.8, 95% CI 1.3-2.6), 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 5.0, 95% CI 2.8-8.2).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.

In epidemiological studies abundant physical activity has been related to decreased breast cancer risk, though the results have been inconsistent. The purpose of this paper was to study the association of physical activity at leisure and commuting to work and incidence of breast cancer.The study cohort consisted of 30,548 female participants of the Finnish adult health behaviour survey, based on annual random samples of Finns aged 15-64, collected in 1978-1993. By the end of 1995, 332 breast cancer cases had been diagnosed in the cohort. Relative risks of breast cancer were adjusted for age at survey, body mass index (BMI), education, length of follow-up, parity and age at first birth using Poisson regression models.Compared to women exercising less than once a week, the adjusted relative risk of breast cancer for women exercising once a week was 0.80 (95% confidence interval (CI): 0.58-1.10), for women exercising 2-3 times per week 0.92 (95% CI: 0.78-1.22) and for women exercising daily 1.01 (95% CI: 0.72-1.42). Women who reported commuting, walking or bicycling to work 30 min or more daily had slightly lower adjusted risk of breast cancer (RR: 0.87, 95% CI: 0.62-1.24) than women working at home, being unemployed or driving a car to working place.Although a small protective effect of regular physical activity for breast cancer incidence was found in physical activity when commuting to work, the role of the physical activity in breast cancer prevention is still an open question.

OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjogren's syndrome (pSS). METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997. RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p

This study was initiated as a consequence of a clinical observation in one hospital of several endometrial carcinomas among users of a fixed combination of a 3-month cycle oral hormonal replacement therapy (HRT), which has been marketed in Finland since 1990. We studied whether the use of 3-month ("long") cycle HRT is accompanied by a higher risk of endometrial cancer than the use of monthly cycle HRT.A nationwide cohort of 15,956 long cycle and 78,549 monthly cycle HRT users since January 1994 was extracted from the files of the national medical reimbursement register and followed up for cancer incidence through the Finnish Cancer Registry up to the end of 1997.There were 61 cases of endometrial cancer among long cycle HRT users which significantly exceeds the average incidence in the Finnish population (standardized incidence ratio (SIRlong) 2.0, 95% confidence interval (CI) 1.6-2.6). The SIR among users of monthly cycle HRT products (SIRmonthly) was 1.3 (1.1-1.6) and the ratio SIRlong/SIRmonthly thus 1.5 (95% CI 1.1-2.1). Endometrial cancers among long cycle HRT users occur more often in early stages than in the general population and are more often highly differentiated. A survey of a sample of endometrial cancer patients in the long cycle HRT group revealed that all of them also had a history of other HRT. Users of both long and monthly cycle HRT had a similar statistically significant 30% excess of breast cancer in comparison to national incidence rates, while the incidence of colon cancer was decreased in both groups. There was no difference between the HRT groups in overall cancer morbidity.Our results imply that all HRT users have an increased risk of endometrial cancer, and long cycle HRT carries a higher relative risk than monthly cycle HRT. However, in this non-randomized setting it is impossible to judge whether this excess is attributable to the type of HRT or to patient selection. In-depth studies are needed to find out possible dose-response associations and to evaluate the role of potential confounders in detail.

Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPC1 at 1q24-q25 (OMIM #601518) and HPCX at Xq27-q28 (OMIM #300147). Genetically homogeneous populations, such as that of Finland, and distinct subsets of families may help to minimize the genetic heterogeneity that complicates the genetic dissection of complex traits. Here, the role of the HPC1, and HPCX loci in a series of Finnish prostate cancer families was studied, especially in subgroups of families defined by age, number of affected cases, and the mode of disease transmission. DNA samples were collected from 57 Finnish HPC families with at least two living prostate cancer patients. Linkage analysis was carried out with 39 microsatellite markers for the HPC1 region and 22 markers for the HPCX region. The maximum two-point LOD score for the HPCX was 2.05 (marker DXS1205, at theta = 0.14), whereas HPC1 LOD scores were all negative. In HOMOG3R analyses, significant evidence of heterogeneity was observed. Subgroup analyses performed to explore the nature of this heterogeneity indicated that families with no male-to-male (NMM) transmission and a late age of diagnosis (65 years) accounted for most of the HPCX-linked cases. The maximum HPCX LOD score in this subgroup was 3.12 (theta = 0.001). Nonparametric sibling pair analyses gave a peak LOD score of 3.04 (P0.000093) for the NMM transmission subgroup. No subgroup showed any positivity for HPC1. This study suggests that the HPCX-linked prostate cancer families represent a distinct subgroup characterized by NMM transmission of disease and late age of diagnosis.

Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown.To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC.Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries.One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls.Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels.Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P.001 for trend).Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.

Identification of predisposition loci to complex diseases, such as prostate cancer, requires high-quality family material, the ascertainment of which is often laborious, time-consuming and inaccurate with conventional methods. Here, we describe a new method for rapid, nationwide cancer family ascertainment using Finnish Cancer Registry data on 35,761 prostate cancer cases over a 40-year period. As members of a prostate cancer family are likely to share the same family name and place of birth, we stratified all prostate cancer cases by these 2 parameters (10,721 different names and 596 municipalities). Data were compared with the distribution of family names and places of birth for all 3.3 million Finnish men to derive standardized prevalence ratios (SPRs). A significantly elevated SPR of prostate cancer was detected for 468 (1.6%) of the 28,459 evaluable combinations of family name and place of birth. Of the 20 highest SPR values, 19 corresponded to true nuclear families, most of these having 3 or more affected cases. Two-thirds of our 50 previously established Finnish prostate cancer families were classified among this 1.6% fraction of the highest SPR values. Finally, many of the highest SPR values originated from municipalities in southern and south-western Finland. To explore whether such clusters could highlight local founder effects, we applied genealogical research to link together several families with elevated SPRs and identified an extended family with 20 prostate cancer cases with common ancestors in the early seventeenth century. In summary, a rapid novel method was developed and validated for identification of prostate cancer families from nationwide cancer registry data and for the identification of putative regional founder effects.

The aim of this study was to investigate whether patients with basal-cell carcinoma (BCC) of the skin have an increased risk of developing other cancers. A total of 71,924 patients diagnosed with BCC between 1953 and 1995 were identified from the Finnish Cancer Registry. They were followed up for subsequent primary cancers from the date of the first BCC diagnosis to the end of 1995. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated based on national rates. Altogether 11,042 subsequent primary cancers occurred among the study cohort during 625,000 person-years of follow-up. Risk increases were observed for non-melanoma skin cancer (SIR 3.79, 95% CI 3.59-4.00) and skin melanoma (SIR 2.34, 95% CI 2.08-2.61). The five other primary sites presenting the highest SIRs were salivary glands (SIR 3.30), lip (2. 19), small intestine (1.85), nose (1.73) and pharynx (1.71). Patients who were less than 40 years of age at the time of BCC diagnosis had a significantly higher relative risk for a subsequent new cancer than the older patients (ratio of the SIRs 1.29, 95% CI 1. 10-1.51). Time since BCC diagnosis did not materially influence the overall relative risk of subsequent cancers. Part of the increase in the risk of skin cancer is likely to be due to enhanced diagnostic activity after an initial diagnosis of BCC. However, the increases in the risk of several non-cutaneous cancers suggest a generalized carcinogenic role of some factors in the BCC pathogenic pathways.

We evaluate the validity of the family history of breast cancer reported by the patient and the number of families and individuals at risk and potentially benefiting from surveillance. Family history of cancer was systematically screened in three different series of breast cancer patients. Breast cancer families were defined by the selection criterion of at least three first- or second-degree relatives with breast or ovarian cancer (including the proband) and their genealogy and cancer diagnoses were confirmed. Family history of breast or ovarian cancer was reported by approximately 30% of the patients and 7-9% were classified as breast cancer families. On average, there were 3.1 healthy female (age: 20-70 years) first degree relatives per family potentially at high risk. Index patients reported 87% of all confirmed diagnoses and the primary site was correct in 93-95% of the reported cases. The incompleteness and errors in accuracy should be considered in epidemiological studies and verification of the diagnoses is important when deciding clinical management.

Twin studies integrate genetic and environmental (including physical environment and life-style) information by comparing monozygotic and dizygotic twins for the occurrence of disease. Our objectives were to compare cancer incidence in twins with national rates and to estimate both the probability that co-twins of affected twins may develop cancer and the importance of genetic predisposition and environment in cancer development. The nationwide record linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow-up of 12,941 same-sexed twin pairs for incident primary cancers from 1976 to 1995. Zygosity was determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting of structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that among the general population. Monozygotic co-twins of affected twins were at 50% higher risk than were dizygotic co-twins. Based on genetic modeling, inherited genetic factors accounted for 18% (95% confidence interval 4-32%) of the liability in inter-individual variation in the risk of overall cancer, while non-genetic factors shared by twins accounted for 7% (0-16%) and unique environmental factors for 75% (65-85%). Our results appear to exclude a contribution greater than one-third for genetic predisposition in the development of cancer in the general population, thus pointing to the earlier confirmed substantial role of environment.

It has been suggested that trioxsalen bath and ultraviolet (UV) A (PUVA) is associated with a very low or no risk of non-melanoma skin cancer, but the numbers of patients in individual studies have been limited. In order to attain statistically relevant information about the cancer risk associated with trioxsalen bath PUVA, two follow-up studies were combined and the joined cancer incidence was analysed among 944 Swedish and Finnish patients with psoriasis. The mean follow-up time for skin cancer was 14.7 years. Standardized incidence ratios (SIR) were calculated as a ratio of observed and expected numbers of cases. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. There was no excess of squamous cell skin carcinoma [SIR 1.1, 95% confidence interval (CI) 0.2-3.2] or malignant melanoma (SIR 0.9, 95% CI 0.1-3.2) in the combined cohort. Basal cell skin carcinoma was not studied. The incidence of all non-cutaneous cancers was not increased (SIR 1.1, 95% CI 0.8-1.4). A threefold excess risk of squamous cell skin carcinoma after trioxsalen bath PUVA could therefore be excluded, which is a markedly lower risk than that associated with oral 8-methoxypsoralen PUVA. The result needs to be confirmed in a future follow-up, however, as the number of patients with high PUVA exposures was low.

Six statistics are compared in a simulation study for their ability to identify geographical areas with a known excess incidence of a rare disease. The statistics are the standardized incidence ratio, the empirical Bayes method of Clayton and Kaldor, Poisson probability, a statistic based on the 'Breslow T' test (BT) and two statistics based on the 'Potthoff-Whittinghill' test (PW) for extra-Poisson variance. Two alternative processes of clustering are simulated in which high-risk locations could be caused by environmental sources or could be sites of microepidemics of an infectious agent contributing to a rare disease such as childhood leukaemia. The simulation processes use two parameters (proportion of cases found in clusters and mean cluster size) which are varied to embrace a variety of situations. Real and artificial data sets of small area populations are considered. The most extreme of the artificial sets has all areas of equal population size. The other data sets use the small census areas (municipalities) in Finland since these have extremely heterogeneous population size distribution. Subset selection allows examination of this variability. Receiver operator curve methodology is used to compare the efficacy of the statistics in identifying the cluster areas; statistics are compared for the proportion of true high-risk areas identified in the top 1 per cent and 10 per cent of ranked areas. One of the PW statistics performed consistently well under all circumstances, although the results for the BT statistic were marginally better when only the top 1 per cent of ranked areas was considered. The standardized incidence ratio performed consistently worst.

To describe the cancer risk pattern of Finnish persons with visual impairment.A cohort of 17,557 persons identified from the Finnish Register of Visual Impairment was followed-up for cancer through the Finnish Cancer Registry from 1983-95. The degree of visual impairment ranged from moderate low vision with visual acuity less than 0.3, to total blindness with no perception of light. The standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated by primary site; the expected rates were based on national cancer incidence rates.The SIR for overall cancer among totally blind men was 2.2 (CI = 1.3-3.5) while in the entire cohort the incidence was increased by only 15% (1,255 cancers observed cf 1,093 expected). Excesses were observed in both genders in cancers of the liver (SIR = 1.8, CI = 1.2-2.5) and lung (SIR = 1.5, CI = 1.3-1.7); in females in cancers of the stomach (SIR = 1.5, CI = 1.2-1.9) and the colorectum (SIR = 1.3, CI = 1.1-1.6); and in males in cancers of the kidney (SIR = 1.8, CI = 1.1-2.6) and the eye (5.8, CI = 1.9-13). The excess in lung cancer was entirely attributable to age-related macular degeneration (which is most common among smokers).Cancer incidence among the visually impaired tended to be increased for most cancer types. Attention should be paid to lifestyle factors underlying the observed risk increases, such as unbalanced diet.

To study the asbestos-associated risk of lung cancer according to the histological type of cancer, the time of and time since diagnosis of asbestosis, the asbestos-associated risk for cancers other than lung cancer or mesothelioma, and the predictive value of asbestos-related pleural abnormalities as regards the risk of cancer.Finnish patients with asbestosis (n = 1,376) or asbestos-related benign pleural disease (n = 4,887) notified as an occupational disease since 1964 were followed-up through the Finnish Cancer Registry for cancer in 1967-95.Compared with the total cancer incidence in Finland, men with asbestosis had a raised risk of lung cancer (standardized incidence ratio [SIR] = 6.7; 95% confidence interval [CI] = 5.6-7.9), mesothelioma (SIR = 32, CI = 14-60) and cancer of the larynx (SIR = 4.2, CI = 1.4-9.8). The risk of lung cancer was similarly raised for all histological types of lung cancer (the highest in insulators) and did not change markedly over time of notification or duration of follow-up. Men with benign pleural disease had a raised risk of mesothelioma (SIR = 5.5, CI = 1.5-14) and a slightly elevated risk of lung cancer (SIR = 1.3, CI = 1.0-1.8). Among women with asbestosis, significant excess was found for lung cancer and mesothelioma.Asbestosis and asbestos-related benign pleural disease seem to possess different predictive values as regards the risk of lung cancer.

Nationwide, computer-based reporting of all arthroplasties performed in Finland was started in January 1980. Using data from these records, a cohort of 31,651 polyethylene-on-metal total hip arthroplasty (THA) patients was followed up for cancer, using Finnish Cancer Registry data, from 1980 to 1995. During follow-up, 2,367 cancers were observed. There were statistically significantly fewer cancers among the THA patients (standardized incidence ratio [SIR], 0.90; 95% confidence interval [CI], 0.87-0.93). SIRs for cancers of the lung (0.69) and stomach (0.77) were significantly below unity. There was no significantly increased risk at any site. The SIR for cancer overall in male THA patients was below unity during the first 3 years after THA but returned to unity thereafter. The low SIR among men during the first 3 years was largely because the lung cancer SIR was 0.47 (95% CI, 0.35-0.62). In women, the SIR remained around 0.93 throughout follow-up. The SIR for stomach cancer was below unity only in women (SIR, 0.67; 95% CI, 0.51-0.86). For cancer of the urinary bladder, the SIR during the first 3 years after THA was below unity but later slightly above it (SIR, 1.24 in relation toor =3 years of follow-up; 95% CI, 0.99-1.52). For myeloma and leukemia, SIRs were greater than unity only for THA patients followed up for 3 to 9 years. The study findings, in contrast to previously reported findings, do not indicate that there is any increased risk of hematopoietic cancers after THA using polyethylene-on-metal prostheses. SIRs relating to soft tissue cancers and bone sarcomas did not differ significantly from unity. No sarcoma was observed at the site of a prosthesis. THA seems to play no major role in cancer causation.

Excessive incidence of various cancers is a challenging feature of the hereditary-non-polyposis-colorectal-cancer (HNPCC) syndrome. This study estimated the cancer incidences in HNPCC compared with the general population. Individuals in a cohort of 1763 members of 50 genetically diagnosed families were categorized according to their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being a carrier. Incidences of cancers in these groups were compared with those in the Finnish population overall. In 360 mutation carriers, standardized incidence ratios (SIR) were significantly increased for colorectal [68; 95% confidence intervals (CI), 56 to 81], endometrial (62; 95% CI, 44 to 86), ovarian (13; 95% CI, 5.3 to 25), gastric (6.9; 95% CI, 3.6 to 12), biliary tract (9.1; 95% CI, 1.1 to 33), uro-epithelial (7.6; 95% CI, 2.5 to 18) and kidney (4.7; 95% CI, 1 to 14) cancers and for central-nervous-system tumours (4.5; 95% CI, 1.2 to 12). The SIR increased with increasing likelihood of being a mutation carrier. The cumulative cancer incidences were 82, 60, 13 and 12% for colorectal, endometrial, gastric and ovarian cancers respectively. For other tumours associated with increased risk, corresponding incidences were below 4%. Interestingly, the incidence of endometrial cancer (60%) exceeded that for colorectal cancer in women (54%). The tumour spectrum associated with germline mutations of DNA-mismatch-repair genes involves 8 or more organ sites, suggesting a need to develop methods to screen for extra-colonic cancer also.

This population-based study investigated the occurrence of breast cancer over a 20-year period in a cohort of monozygotic (MZ) and dizygotic (DZ) twins in Finland. Altogether, 13,176 female twins of known zygosity who were living in Finland at the end of 1975 were identified from the Finnish Twin Cohort Study and followed-up for cancer through the Finnish Cancer Registry for the years 1976-1995. Standardized incidence ratios (SIRs) were calculated, based on national cancer incidence rates. The relative risk of breast cancer for MZ twins compared to DZ twins was decreased [SIR(MZ)/SIR(DZ) ratio = 0.78; 95% confidence interval (CI), 0.58-1.0]; the decreased risk for MZ twins (SIR = 0.76; 95% CI, 0.58-1.0) accounted for this result, whereas the risk for DZ twins did not differ from the general population risk (SIR = 0.98; 95% CI, 0.84-1.1). There was no risk decrease among MZ twins in other cancers related to reproductive behavior; i.e., number of children and age at first birth seem not to explain the decreased risk of breast cancer. Our results, which are in line with earlier studies on the same topic, suggest that prenatal influences or postnatal behavioral factors may protect MZ female twins from breast cancer.

Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.

Chlorination of water rich in organic material is known to produce a complex mixture of organochlorine compounds, including mutagenic and carcinogenic substances. A historical cohort study of 621,431 persons living in 56 towns in Finland was conducted in order to assess the relation between historical exposure to drinking water mutagenicity and cancer. Exposure to quantity of mutagenicity was calculated on the basis of historical information of raw water quality and water treatment practices using an empirical equation relating mutagenicity and raw water pH, KMnO4 value and chlorine dose. Cancer cases were derived from the population-based Finnish Cancer Registry and follow-up time in the study started in 1970. Age, gender, time period, social class, and urban residence were taken into account in Poisson regression analysis of the observed numbers of cases using expected numbers of cases standardized for age and gender as a basis. Excess risks were calculated using a continuous variable for mutagenicity for 3,000 net rev/l exposure representing an average exposure in a town using chlorinated surface water. After adjustment for confounding, a statistically significant excess risk was observed for women in cancers of the bladder (relative risk [RR] = 1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI = 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11, CI = 1.01-1.22). These results support the magnitude of excess risks for rectal and bladder cancers found in earlier epidemiologic studies on chlorination by-products and give additional information on exposure-response concerning the mutagenic compounds. Nevertheless, due to the public health importance of water chlorination, uncertainty related to the magnitude of observed risks, and the fact that excess risks were observed only for women, the results of the study should be interpreted with caution.

The risk of hematologic malignancies was studied in Finnish patients with rheumatoid arthritis or Sjögren's syndrome, and the difference in the risk between those diseases was evaluated. The study cohorts comprised 676 patients with primary Sjögren's syndrome, 709 with secondary Sjögren's syndrome, and 9,469 with rheumatoid arthritis identified from the Finnish hospitals' national discharge register. The follow-up times were 5,336, 4,254 and 65,391 person-years, respectively. Data on the incidence of malignancies were collected from the files of the Finnish Cancer Registry. The incidence of hematologic malignancies was elevated in the study cohorts. The standardized incidence ratio (SIR) of non-Hodgkin's lymphoma was: 2.2 (95 percent confidence interval [CI] 1.5-3.1) for rheumatoid arthritis; 4.5 (CI = 1.5-11) for secondary Sjögren's syndrome; and 8.7 (CI = 4.3-16) for primary Sjögren's syndrome. The ratio of the SIR of primary Sjögren's syndrome cf rheumatoid arthritis alone was 3.9 (CI = 1.8-8.0) in non-Hodgkin's lymphoma, and 3.4 (CI = 1.2-8.1) in other hematologic cancers. The incidence of hematologic malignancies, especially that of non-Hodgkin's lymphoma, is elevated in patients with rheumatoid arthritis. It is higher in patients with secondary Sjögren's syndrome and highest in patients with primary Sjögren's syndrome. Differences in the immunologic aberration influence oncogenesis.

A cohort of approximately 120,000 male and 85,000 female farmers registered in the Farm Register of Finland was followed-up for cancer incidence through the Finnish Cancer Registry in 1979-93. Nearly 17,000 cancer cases were observed. Compared with the total cancer incidence of the Finnish population, both genders experienced a 17 to 18 percent decreased risk of cancer. The risks were low in smoking-related cancers, cancers associated with an urbanized way of life, and cancers inversely associated with multiparity. The only cancer sites showing significantly raised standardized incidence ratios (SIR) were lip cancer (SIR = 1.51, 95 percent confidence interval [CI] = 1.35-1.66) and Hodgkin's disease (SIR = 1.35, CI = 1.08-1.67) in males. Poisson regression was used in working out the roles of the size and type of farm after adjustment for gender, age, and geographic location of the farm. Risk of Hodgkin's disease was highest in farms without animals (SIR = 1.74, CI = 1.12-2.59). Multiple myeloma was found in excess among farmers on pig or poultry farms but not on other types of farms.

A number of chemicals encountered predominantly in occupational settings have been causally linked with cancer in humans; furthermore, several industrial processes and occupations have been associated convincingly with increased rates of cancer, although the specific carcinogens remain to be identified. The tissues affected are mainly the epithelial lining of the respiratory organs (nasal cavity, paranasal sinuses, larynx and lung), and urinary tract (renal parenchyma, renal pelvis and urinary bladder), the mesothelial linings, the bone marrow and the liver. During the period 1970-84, almost 4 million people (3.7 million men and 0.2 million women) in the Nordic countries were potentially exposed to above-average levels of one or more verified industrial carcinogens. It is expected that these exposures will result in a total of about 1,900 new cases of cancer every year in the Nordic countries around the year 2000, with 1,890 among men and fewer than 25 among women. The proportions that could be avoided if industrial carcinogens were eliminated would be 70% of mesotheliomas, 20% of cancers of the nasal cavity and sinuses, 12% of lung cancers, 5% of laryngeal cancers, 2% of urinary bladder cancers, 1% of the leukaemias, and 1% of renal cancers. Overall, it is estimated that verified industrial carcinogens will account for approximately 3% of all cancers in men and less than 0.1% of all cancers in women in the Nordic countries around the year 2000. No attempt was made to estimate the potential effects of suspected carcinogens in the workplace.

Alcohol intake is causally associated with cancers of the larynx, oral cavity, pharynx, oesophagus and liver. In all five Nordic countries, alcohol consumption increased substantially between 1965 (6.5 litres per adult per year) and 1975 (10 litres), but remained at about 10 litres between 1975 and 1985. The daily consumption of men during the period was substantially higher than that of women, and that of both men and women was higher in Denmark than in the other Nordic countries. In about 2000, an annual total of almost 1,300 cancer cases (1,000 in men and 300 in women) would be avoided if alcohol drinking were eliminated. This corresponds to about 29% of all alcohol-related cancers, i.e. in the oesophagus (37%), oral cavity and pharynx (33%), larynx (29%) and liver (15%). About 2% of all cancers in men and 1% in women in the Nordic countries around the year 2000 will be caused by the drinking habits of the respective populations.

Active smoking is causally associated with cancers of the lung, larynx, oral cavity, pharynx, oesophagus, pancreas, renal parenchyma, renal pelvis and urinary bladder, and passive smoking appears to be causally associated with cancer of the lung. Information on smoking habits for the years 1965, 1975 and 1985 shows that more men than women in the Nordic countries were current smokers. The rates of women were stable over time and those of men were decreasing, approaching those of women. Lung cancer, in particular, is strongly associated with active smoking: by increasing the number of cigarettes smoked per day (lifelong) to 5, 10, 20 and 40 or more, the risk increases by five-, eight-, 16- and 30-fold, respectively, over that of people who have never smoked. Thus, with approximately 35% current smokers and 25% former smokers among Nordic men in 1985 and approximately 30% current smokers and 15% former smokers among Nordic women in that year, by the year 2000 10,000 cases of lung cancer (6,500 in men and 3,500 in women) will be caused by active smoking; this is equivalent to 82% of all cases of lung cancer in these populations. Another 6,000 cancers of other types (4,000 in men and 2,000 in women) are caused annually by active smoking, yielding a total of 16,000 new cases each year around the turn of the century. This implies that 14% (19% in men and 9% in women) of all incident cancers in the Nordic countries around the year 2000 will be caused by active tobacco smoking. In comparison, passive smoking is a minor cause of lung cancer, responsible for approximately 0.6% of all new cases (approximately 70 cases annually) in this area around the turn of the century.

Exposure to solar and ionizing radiation increases the risk for cancer in humans. Some 5% of solar radiation is within the ultraviolet spectrum and may cause both malignant melanoma and non-melanocytic skin cancer; the latter is regarded as a benign disease and is accordingly not included in our estimation of avoidable cancers. Under the assumption that the rate of occurrence of malignant melanoma of the buttocks of both men and women and of the scalp of women would apply to all parts of the body in people completely unexposed to solar radiation, it was estimated that approximately 95% of all malignant melanomas arising in the Nordic populations around the year 2000 will be due to exposure to natural ultraviolet radiation, equivalent to an annual number of about 4700 cases, with 2100 in men and 2600 in women, or some 4% of all cancers notified. Exposure to ionizing radiation in the Nordic countries occurs at an average effective dose per capita per year of about 3 mSv (Iceland, 1.1 mSv) from natural sources, and about 1 mSv from man-made sources. While the natural sources are primarily radon in indoor air, natural radionuclides in food, cosmic radiation and gamma radiation from soil and building materials, the man-made sources are dominated by the diagnostic and therapeutic use of ionizing radiation. On the basis of measured levels of radon in Nordic dwellings and associated risk estimates for lung cancer derived from well-conducted epidemiological studies, we estimated that about 180 cases of lung cancer (1% of all lung cancer cases) per year could be avoided in the Nordic countries around the year 2000 if indoor exposure to radon were eliminated, and that an additional 720 cases (6%) could be avoided annually if either radon or tobacco smoking were eliminated. Similarly, it was estimated that the exposure of the Nordic populations to natural sources of ionizing radiation other than radon and to medical sources will each give rise to an annual total of 2120 cancers at various sites. For all types of ionizing radiation, the annual total will be 4420 cancer cases, or 3.9% of all cancers arising in the Nordic populations, with 3.4% in men and 4.4% in women.

The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects.Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors.Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer.Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels.

To study the relationship of polymositis (PM) and dermatomyositis (DM) and cancer in Finland.The medical records of 175 patients with PM and 71 with DM diagnosed between 1969 and 1985 were reviewed. The patients were followed until death or until December 30, 1990 through the files of Statistics Finland and the Finnish Cancer Registry.Thirty-four cases of cancer were found [standardized incidence ratio (SIR) 2.1, 95% confidence interval 1.4-2.9]. In the PM group the SIR was 1.0 (95% CI 0.5-1.8), and in the DM group 6.5 (95% CI 3.9-10). The relative risk of cancer among DM cases was very high (SIR 26, 12-48) in the first year after DM diagnosis.DM is associated with cancer, but not PM. The risk is high among patients with DM older than 49. Cytotoxic drugs given to DM patients did not increase the risk of malignancies. DM and certain cancers seem to share etiological factors.

A cohort of 736 male and 167 female workers of two anthophyllite mines in Finland was followed up through the Finnish Cancer Registry for cancer in 1953-91. Compared with the total cancer incidence of the east Finnish population, the men had a raised risk of total cancer (standardised incidence ratio (SIR) 1.7; 95% confidence interval (95% CI) 1.4-1.9), mainly attributable to an excess in lung cancer (SIR 2.8; 95% CI 2.2-3.6). The risk of lung cancer was somewhat higher among workers classified as heavily exposed (SIR 3.2; 95% CI 2.4-4.1) than among those moderately exposed (SIR 2.3; 95% CI 1.5-3.6) and the risk increased with increasing smoking and with increasing time of work with exposure. There were four cases of mesothelioma v 0.1 expected, all in men who smoked and had had a long and heavy asbestos exposure. Among women, a non-significant excess in total cancer (SIR 1.5; 95% CI 0.9-2.4) was found in the subgroup with heavy exposure to asbestos. Anthophyllite asbestos seems to have high potency in the carcinogenesis of lung cancer and low potency in carcinogenesis of mesothelioma in comparison with the other types of asbestos.

To evaluate the risk of cancer in patients with systemic lupus erythematosus (SLE) a series of 205 consecutive patients (182 women and 23 men) were followed up for cancer through the files of the Finnish Cancer Registry. The follow up consisted of a total of 2340 person years. Fifteen cancers were diagnosed against 5.7 expected (relative risk (RR) 2.6, 95% confidence interval (CI) 1.5 to 4.4). Among the women there were four non-Hodgkin's lymphomas against 0.09 expected (RR 44, CI 11.9 to 111) and two soft tissue sarcomas against 0.04 expected (RR 49, CI 6.0 to 177). When evaluated by a case control study previous treatment with cytostatic drugs showed no influence on the occurrence of cancer in this series of patients with SLE.

The occurrence of second primary cancers in patients with lip cancer was evaluated in order to test certain etiologic hypotheses. All cases of lip cancer reported to the Finnish Cancer Registry in 1953–74 (3303 men, 320 women) were followed up for a second (or third) primary cancer through the files of the Registry either to death or to 31 December 1974 (a total of 25510 person-years). The expected numbers of cases were calculated on the basis of the incidence rates specific for sex, age, time and residence (urban or rural) in Finland. A higher than expected risk of cancer was found among both urban and rural male lip cancer patients; among women the observed number of new primary cancers did not differ from that expected. A significant excess risk among males was noted for cancers of the lung and larynx (rural patients) and for non-melanomatous skin cancer in locations other than the head and neck (urban patients). The association of cancers of the lip, lung and larynx found earlier on a geographic level supports the hypothesis that tobacco smoking is a common risk factor in these cancers. The differences in the relative risks between urban and rural patients, however, suggest that the risk factors in lip cancer in urban areas might be partially different from those prevalent in the rural population. The results do not support the hypothesis that sunlight is an important risk factor in lip cancer.

Names of women eligible to be screened for cervical cancer are taken from the national population registry and the women are invited by a personal letter. The data, from these mass screenings are analysed and stored at the screening registry. To reduced the costs of the system and to increase the yield of preinvasive lesions the idea of selective screening was considered. Tt was decided that if people were selected according to their risk factors, as recorded in the national population registry, the screening would be ineffective as many cases of invasive cancer were found in the low risk groups. High risk factors were determined from anamnestic data on systems and from previous cytological diagnoses. The proportion of women with symptoms of bleeding or the class II-V smears without positive histological results constituted fewer than 10% of the participants, but 20% and 40% respectively of invasive carcinomas were found in these groups during the subsequent follow-up period. Thus it is suggested that selective screening apart from that based on age has a limited application and should be restricted mainly to the interval between the organised screenings, which in Finland is five years.