Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1). OBJECTIVE: To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype. DESIGN: Prospective clinical examination with genetic evaluation and follow-up. SETTING: Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included. METHODS: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for PAVM and neurological evaluation. Blood tests were performed for analysis of disease-causing mutation, and clinical manifestations in the HHT subtypes were compared. The survival of the patients was studied in the follow-up period. RESULTS: Included in the study were 73 HHT patients representing 18 families. In 14 of the families we identified a disease-causing mutation. Thirty-nine patients (from 10 families) had HHT1 and 16 HHT patients from four families had HHT2. CONCLUSION: Amongst patients with HHT1 genotype the prevalence of PAVM was higher than amongst HHT patients with HHT2 genotype. HHT1 patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased.

Cancer in siblings of children with cancer in the Nordic countries: a population-based cohort study.

BACKGROUND: In some rare inherited disorders such as Li-Fraumeni syndrome, relatives of children with cancer are at increased risk of cancer. We aimed to assess relations between childhood cancer and sibling risk, and evaluate the influence of recessive conditions in cancer causation. METHODS: We did a population-based cohort study in the Nordic countries of 42277 siblings of 25605 children with cancer. Children with cancer were identified from records in the five Nordic cancer registries, and their siblings from nationwide population registries. Cancers in siblings were documented through record linkage with cancer registries and compared with national incidence rates. We also assessed cancer incidence in parents to identify familial cancer syndromes. FINDINGS: 284.2 cancers were expected in siblings, whereas 353 were diagnosed (standardised incidence ratio 1.24 95% CI 1.12-1.38). Risk ratios for siblings were highest in the first decade of life (2.59, 1.89-3.46). We excluded 56 families with genetic syndromes linked to cancer, which reduced this ratio from 1.7 to 1.0 (0.7-1.3) for siblings younger than 20 years, and from 1.3 to 1.0 (0.8-1.3) for those aged 20-29 years. We found no new patterns of familial cancer that indicated inherited susceptibility, or evidence that recessive conditions might contribute to cancers not explained by syndromes. 40% of cancers in siblings that occurred before age 20 years could be attributed to known genetic factors, whereas 60% remained unexplained. INTERPRETATION: Apart from rare cancer syndromes, paediatric cancer is not an indicator of increased cancer risk in siblings.

A population-based cohort study of HRT use and breast cancer in southern Sweden.

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.

Decreasing late mortality among five-year survivors of cancer in childhood and adolescence: a population-based study in the Nordic countries.

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 pattern of causes of death varied markedly between different groups of primary cancer diagnoses and was highly dependent on time passed since diagnosis. Overall late mortality was significantly lower in patients treated during the most recent period of time, 1980 to 1989, compared with those treated from 1960 to 1979 (hazard ratio, 0.61; 95% CI, 0.54 to 0.70), and there was no increase in rates of death due to cancer treatment. CONCLUSION: 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.

Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register.

This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 198688 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.

Survival of children with liver tumours in Europe 1978--1989.

Hepatic tumours are rare in childhood. Within the frame of the EUROCARE II study, a total of 328 liver tumours in patients aged 0--14 years were reported during the period 1978--1989. The childhood cancer registries in UK and Germany contributed approximately a third of the cases each. Hepatoblastoma accounted for 71% of cases. The 5-year survival was 36% 95% confidence interval (CI) 28--46%, with no significant difference between the genders. Patients aged 10--14 years did worse, especially boys. Survival improved significantly during the study period. Survival in hepatocellular carcinoma was lower, 20% (95% CI 6--52%), and showed no improvement during the study period.

Familial breast and ovarian cancer: a Swedish population-based register study.

A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national calendar year-, age-, and sex-specific incidences. For daughters of women with breast cancer, the standardized morbidity ratios for being diagnosed with breast cancer and ovarian cancer before age 50 years were 1.99 (95% confidence interval (CI): 1.86, 2.14) and 1.28 (95% CI: 1.05, 1.54), respectively. The corresponding figures for daughters of women with ovarian cancer were 1.79 (95% CI: 1.55, 2.07) and 2.38 (95% CI: 1.77, 3.12). The risks were raised if the mother's cancer was diagnosed at a young age, the mother had multiple breast/ovarian diagnoses, or there was a sister with breast/ovarian cancer. Among all offspring, increased risks were found for thyroid cancer, testicular cancer, and malignant melanoma, while lung cancer risk was decreased if the mother had had breast cancer. The authors developed a variance estimator for the standardized morbidity ratio to cope with overdispersion due to dependency within families.

Impact of a cancer education multimedia device on public knowledge, attitudes, and behaviors: a controlled intervention study in Southern Sweden.

BACKGROUND: The objective was to determine the impact of a multimedia device offering information about malignant melanoma on public knowledge, attitudes, and behaviors. METHODS: Two municipalities in Sweden, Dalby and S Sandby, were chosen. The population of Dalby was exposed to the multimedia program during 1994-97, whereas the S Sandby population was not. A questionnaire was sent to random samples of the populations (10% of those aged 20-59 years) before (1994, n = 373 and n = 409, respectively) and after the intervention (1996, n = 375 and n = 418, respectively). Response rates were 74-89%. RESULTS: The groups were well balanced at baseline. In both areas women scored higher both at baseline and in 1996. Dalby women showed less fear of skin cancer in 1996 than in 1994 (2.13 vs 2.27, p < 0.01). This was not so in the controls. There was no major change in "sun behavior" in Dalby, whereas there was a negative change in S Sandby. After the intervention Dalby men had more "knowledge" (from 2.64 to 2.70, p < 0.05) and a tendency to better "sun behavior" (from 1.77 to 1.85, p = 0.076). There was no significant change over time in the S Sandby men. CONCLUSIONS: The multimedia program had a modest effect. The population in Dalby had more knowledge and changed its attitudes in a sun-protective direction. In the control area, the two-year follow-up sun behavior score was lower than at baseline. There was also significantly less fear of skin cancer after the intervention.

Carcinoma of the hypopharynx: analysis of incidence and survival in Sweden over a 30-year period.

BACKGROUND: The aim of the study was to analyze whether there were any changes in incidence and prognosis of hypopharyngeal carcinomas diagnosed between 1960 and 1989 in Sweden. METHODS: Data of primary hypopharyngeal malignant tumors reported to the Swedish Cancer Registry were collected. The total number of cases was 2012, 1396 men and 616 women, and the end of follow-up was December 31, 1992. RESULTS: For women, a significant decrease in the age-standardized incidence (ASI) was seen, with an average decrease of 2% per year (p < .001), which was most evident in rural counties. The male patients, on the contrary, showed a significant increase of about 1.5% per year (p < .001); the metropolitan areas had an ASI about twice that of more-rural areas. The 2- and 5-year overall survival was poor, only 25% and 13%, respectively. For women aged <60 years, no difference in survival between the different 10-year periods was seen, but survival for men of corresponding ages improved significantly (p < .01) during the last decade, to reach a survival similar to that in women. For patients aged > or = 60 years, no difference in survival between the different periods or between sexes was seen. CONCLUSION: The increased incidence in hypopharyngeal cancer in men is similar to that observed for oral and pharyngeal cancer in many European countries during this period. The disappearance of Plummer-Vinson syndrome may explain the decreased incidence among women. The treatment results in hypopharyngeal cancer are still very poor, and improvements of the therapeutic methods are needed.

Relative survival of cancer patients--a comparison between Denmark and the other Nordic countries.

The results of a Nordic collaborative project revealed that Danish cancer patients had a poorer prognosis than patients in the other Nordic countries for some major cancer sites. The present study was undertaken to further explore the differences in survival between Denmark and the other Nordic countries. All cancer cases diagnosed in the Nordic countries during 1958 to 1991/92 were included in the analysis. Relative survival and excess mortality were calculated for intervals in the first five years after diagnosis. Since the 1950s, the prognosis of cancer patients has improved in all the countries, but more moderately in Denmark. For cancers of the stomach, colon, rectum, breast (female), and prostate, the Danish patients had a markedly lower relative survival than the patients in the other countries. They also had the lowest proportion of localized tumours. It appears that Danish cancer patients are diagnosed at a later stage of disease than patients in the other Nordic countries.

Acceptance by Swedish users of a multimedia program for primary and secondary prevention of malignant melanoma.

BACKGROUND: In Sweden, the incidence of malignant melanoma of the skin is rapidly increasing, and the disease is now one of the ten most common tumor types. The objectives were to apply multimedia techniques to increase public knowledge about malignant melanoma and its risk factors, to increase awareness of preventive measures, and to make people more disposed to change their sunbathing habits. METHODS: A trilingual (Swedish, English, and German) multimedia program was developed for two target groups, health care personnel and the general public, with a total of >500 "pages" in each language. User reactions were studied on-site at a municipal pharmacy and library, where the program was available in a kiosk with touch-screen. RESULTS: Practically all 274 users interviewed found the program easy to use and understand. 92% identified one or more of the recommendations given. 66% found the program information "worrying," and 29%--mainly young women-instantly declared that they were going to change their sun-exposure behaviors. No correlation to skin type was found. CONCLUSIONS: A multimedia program of the present design seems to be a useful tool for health promotion.

Population-based cohort investigations of the risk for malignant tumors in first-degree relatives and wives of men with breast cancer.

BACKGROUND: Retrospective studies of familial cancer risks could be subjected to bias and should be supplemented with prospective studies if possible. Few such studies exist, and no prospective population-based study has addressed the risk for malignant tumors among relatives or wives of men with breast cancer. METHODS: All first-degree relatives and wives of 153 men whose conditions were diagnosed as male breast cancer from 1965 to 1989 in the southern health-care region of Sweden were identified through parish data. Relatives and wives alive January 1, 1958, were included in two cohorts. Their vital status and cancer morbidity were studied in the Swedish Cancer Registry, Cause of Death Registry, and Census Registry. RESULTS: The incidence for malignant tumors was significantly increased among female first-degree relatives (standardized morbidity ratio [SMR], 1.36). Significantly elevated SMR were seen for breast carcinoma (SMR, 1.80), ovarian carcinoma (SMR, 2.27), and cancer of the parotid gland (SMR, 5.58). Elevated nonsignificant SMR were seen for cancer of the cervix uteri and for bone and soft tissue sarcoma. An almost significant decreased overall cancer incidence was seen for male first-degree relatives (SMR, 0.75). The most pronounced decrease was seen for cancer of the prostate. The increased breast cancer incidence in female relatives were present in mothers, sisters, and daughters. The overall tumor incidence was not increased (SMR, 0.98) in wives of men with breast cancer. There was no significant increase in breast cancer incidence (SMR, 0.97). CONCLUSIONS: Female first-degree relatives of men with breast cancer have an elevated incidence of breast cancer and other female genital tumors, whereas male first-degree relatives have a reduced cancer incidence. Wives of men with breast cancer have a similar cancer incidence as the general population.

Early oral contraceptive use and premenopausal breast cancer--a review of studies performed in southern Sweden.

In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.

Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden.

In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.

Cancer incidence after cholecystectomy--a cohort study with 30 years follow-up.

Cholecystectomy has been connected with an increase in colorectal, breast and reproductive system cancers. On 472 patients, 398 women and 74 men, cholecystectomized during the years 1951 to 1955, cancer incidence was investigated. Our results show an elevated risk of breast cancer in the female group (P = 0.016), but no significant increased risk in colorectal or gynaecologic cancer. The risk for breast cancer increased with time after operation. In our small group of men an elevated SMR was noted for colon cancer without reaching statistical significance. Possible aetiological factors for the association between cholecystectomy and breast cancer are discussed.

Early oral contraceptive use as a prognostic factor in breast cancer.

The survival of 193 premenopausal breast cancer patients was investigated in relation to their history of early use of oral contraceptives. The women were born in 1939 or later and diagnosed in the southern health care region of Sweden. Women, who had started their oral contraceptive use (OC-use) before 20 years of age had a significantly lower survival rate as compared with those who had never used OC and late users (p = 0.02 and = 0.04 respectively, generalized Wilcoxon test). For women who started OC-use between 20 to 25 years of age, a tendency for a shorter survival was seen in comparison with women who had never used OC (p = 0.18). For all patients simultaneously, the relative risk adjusted for age at diagnosis increased for earlier OC-start. When only stages II and III were considered in a stratified multivariate model, a significantly elevated risk was seen for early users of OC irrespective of age or of adjuvant treatment given. The estrogen and progesterone receptor concentrations of the primary tumor were significantly lower among early users (p = 0.001 and p = 0.05 respectively).

PIP: The survival of 193 premenopausal breast cancer patients was analyzed in terms of onset of use of oral contraceptives: earlier use of pills predicted shorter survival times. 193 consecutive breast cancer premenopausal patients, from the southern region of Sweden diagnosed at University of Lund, were staged and interviewed for age when starting pills, duration, and brand. Women who started orals before age 20 had significantly shorter survival rates than never-users or late users (p=0.02 and 0.04). Women who started orals between 20-25 years of age showed a tendency toward shorter survival compared to never users (p=0.18). The relative risks, adjusted for age at diagnosis, increased in proportion to earlier age of onset of pill use (never = 1.0; 25 = 0.7; 20-25 = 2.8; 20 = 9.2). When only cancer stages II and II were considered in a multivariate model, a significantly elevated risk appeared for early users regardless of age or treatment given. The estrogen and progesterone receptor concentrations in the primary tumor were significantly lower among early users (p=0.001 and 0.05). These findings are consistent with previously reported larger tumor size, higher frequency of axillary metastases and altered hormone receptor status in early pill users.