Cancer incidence among Nordic airline cabin crew.

Airline cabin crew are occupationally exposed to cosmic radiation and jet lag with potential disruption of circadian rhythms. This study assesses the influence of work-related factors in cancer incidence of cabin crew members. A cohort of 8,507 female and 1,559 male airline cabin attendants from Finland, Iceland, Norway and Sweden was followed for cancer incidence for a mean follow-up time of 23.6 years through the national cancer registries. Standardized incidence ratios (SIRs) were defined as ratios of observed and expected numbers of cases. A case-control study nested in the cohort (excluding Norway) was conducted to assess the relation between the estimated cumulative cosmic radiation dose and cumulative number of flights crossing six time zones (indicator of circadian disruption) and cancer risk. Analysis of breast cancer was adjusted for parity and age at first live birth. Among female cabin crew, a significantly increased incidence was observed for breast cancer [SIR 1.50, 95% confidence interval (95% CI) 1.32-1.69], leukemia (1.89, 95% CI 1.03-3.17) and skin melanoma (1.85, 95% CI 1.41-2.38). Among men, significant excesses in skin melanoma (3.00, 95% CI 1.78-4.74), nonmelanoma skin cancer (2.47, 95% CI 1.18-4.53), Kaposi sarcoma (86.0, 95% CI 41.2-158) and alcohol-related cancers (combined SIR 3.12, 95% CI 1.95-4.72) were found. This large study with complete follow-up and comprehensive cancer incidence data shows an increased incidence of several cancers, but according to the case-control analysis, excesses appear not to be related to the cosmic radiation or circadian disruptions from crossing multiple time zones.

Milk intake in early life and risk of advanced prostate cancer.

The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.

Rye bread consumption in early life and reduced risk of advanced prostate cancer.

OBJECTIVE: To determine whether consumption of whole-grain rye bread, oatmeal, and whole-wheat bread, during different periods of life, is associated with risk of prostate cancer (PCa). METHODS: From 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed for early life, midlife, and current life using a validated food frequency questionnaire. Through linkage to cancer and mortality registers, we retrieved information on PCa diagnosis and mortality through 2009. We used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for PCa according to whole-grain consumption, adjusted for possible confounding factors including fish, fish liver oil, meat, and milk intake. RESULTS: Of the 2,268 men, 347 had or were diagnosed with PCa during follow-up, 63 with advanced disease (stage 3+ or died of PCa). Daily rye bread consumption in adolescence (vs. less than daily) was associated with a decreased risk of PCa diagnosis (OR = 0.76, 95 % confidence interval (CI): 0.59-0.98) and of advanced PCa (OR = 0.47, 95 % CI: 0.27-0.84). High intake of oatmeal in adolescence (≥5 vs. ≤4 times/week) was not significantly associated with risk of PCa diagnosis (OR = 0.99, 95 % CI: 0.77-1.27) nor advanced PCa (OR = 0.67, 95 % CI: 0.37-1.20). Midlife and late life consumption of rye bread, oatmeal, or whole-wheat bread was not associated with PCa risk. CONCLUSION: Our results suggest that rye bread consumption in adolescence may be associated with reduced risk of PCa, particularly advanced disease.

Familiality of benign and malignant paraproteinemias. A population-based cancer-registry study of multiple myeloma families.

BACKGROUND AND OBJECTIVES: The occurrence of two or more cases of multiple myeloma (MM) in the same family has been reported from time to time. The current study is the first population- and cancer-registry-based survey to investigate familiality of premalignant or malignant B-cell proliferation. DESIGN AND METHODS: A family registry of 218 multiple myeloma cases was compared with the records of the Icelandic Cancer Registry in order to analyze the pedigrees for the occurrence of families with multiple cases of paraproteinemia and hematologic malignancies. RESULTS: The relative risk of developing monoclonal gammopathies of unknown significance (MGUS) was not increased among first-degree relatives of MM patients, but there was a significantly increased risk of developing MM for females separately (RR = 3.23, CI 1.17-7.01) and for males and females combined (RR = 2.33, CI 1.12-4.26). Analysis for all hematologic malignancies showed an increased risk for female relatives of MM patients (RR = 1.95, CI 1.10-3.20). Eight families were identified in which the propositus with MM had > 1 relatives with MGUS and > 1 with another hematologic malignancy, including 4 families with another relative with MM. In three families both myeloid and lymphoid malignancies occurred. INTERPRETATION AND CONCLUSIONS: Although inheritance does not appear to be a major risk factor for the development of paraproteinemias a significant risk of developing MM was found for female relatives. The occurrence of multiple cases of benign and malignant paraproteinemias in a few families does suggest a hereditary contribution. Further studies of such families might reveal clues on pathogenesis.

BRCA2 mutation carriers, reproductive factors and breast cancer risk.

BACKGROUND: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear. METHODS: In a case-control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis. RESULTS: An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years. CONCLUSION: The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.

Genetic epidemiologic aspects of gastric cancer in Iceland.

BACKGROUND: Association between gastric cancer and environmental factors (diet and infections) has been established, and genetic changes are well described in adenocarcinomas of the stomach. Less is known about clinical features of hereditary gastric cancer and whether the disease is associated with family clustering. STUDY DESIGN: Family trees of patients diagnosed with gastric cancer in Iceland between 1955 and 1999 were identified in the Genealogical Database of the University of Iceland. All probands with age of onset younger than 60 years were used in the study. Families of all probands (n = 455 men and 161 women) were traced to third degree. Through linkage of the genealogic data obtained by the Icelandic Cancer Registry (between 1955 and 1999), all reported cancers were identified in those families. The expected number of cases was calculated using age-specific population rates in Iceland. RESULTS: A relative risk (RR) of 2.2 (95% confidence interval [CI] = 1.6-3.0) and 1.3 (95% CI = 1.0-1.7) for the gastric cancer risk was observed among 2,846 first- and 8,658 second-degree relatives of male probands. For female probands the corresponding relative risks were 1.6 (95% CI = 1.1-2.6, n = 7,396) and 1.4 (95% CI = 0.9-2.0, n = 2,764). The increased risk was more pronounced for relatives of men and women diagnosed with gastric cancer before the age of 50 years. A minor difference in relative risk was found between relatives of probands who were diagnosed with intestinal type or diffuse type gastric cancer. Fifty-eight families with two or more relatives with cancer were identified. In 32 families 2 relatives with gastric cancer were identified and in 26 families 3 or more relatives had gastric cancer. CONCLUSIONS: Relatives of gastric cancer patients have two- to three-fold increased risk of developing gastric cancer. The risk is elevated for both genders.

[Cancer in siblings of children with cancer]. / Cancer hos søskende til børn med cancer.

INTRODUCTION: 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. MATERIAL AND METHODS: We did a population-based cohort study in the Nordic countries of 42,277 siblings of 25,605 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. RESULTS: 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. DISCUSSION: Apart from rare cancer syndromes, paediatric cancer is not an indicator of increased risk in siblings.

The use of genealogy databases for risk assessment in genetic health service: a systematic review.

UNLABELLED: The use of electronic genealogical databases facilitates the construction of accurate and extensive pedigrees for potential use in genetic services. Genealogy databases can be linked to specific disease databases, such as cancer registries, in order to increase the accuracy of pedigrees used, and inform the genetic risk assessment. To review the published literature on the use of genealogy databases to construct pedigrees for risk assessment in genetic health service, a systematic literature search was undertaken using 12 combined search terms to identify all relevant published articles. DATA SOURCES: EbscoHost, PubMed, Web of Science, Ovid and the "grey literature", as well as the reference lists of identified studies. Of 1,035 titles identified, two papers described a study on the use of genealogy databases in cancer risk assessment and two were discussion papers. While authors of the four papers described the potential use of genealogy databases in clinical genetic services, such use has not been adequately investigated and further research is required.

Consumption of fish products across the lifespan and prostate cancer risk.

OBJECTIVE: To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer. DESIGN: The study was nested among 2268 men aged 67-96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption. RESULTS: Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption. CONCLUSIONS: Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.

Multigenerational information: the example of the Icelandic Genealogy Database.

The first part of the chapter describes the Icelandic Genealogical Database, how it was created, what it contains, and how it operates. In the second part, an overview of research accomplished with material from the database is given.

Prostate cancer progression and survival in BRCA2 mutation carriers.

BACKGROUND: Mutations in the BRCA2 gene are associated with an increased risk of prostate cancer, but it is not known whether they are associated with progression of the disease. We compared prostate cancer-specific survival, disease stage, and tumor grade between prostate cancer patients carrying the Icelandic BRCA2 999del5 founder mutation and noncarriers. METHODS: Using population-based registries, we identified all 596 prostate cancer patients who were diagnosed in Iceland during 1955 through 2004 among 29603 male relatives of unselected breast cancer probands. BRCA2 mutation status could be determined for 527 patients (88.4%). Stage and grade were abstracted from original records, blindly with respect to mutation status, for a subgroup of 89 patients that included all mutation carriers and, for each carrier, two control patients without the BRCA2 999del5 mutation who were matched to the carrier on years of diagnosis and birth. Hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer-specific survival were estimated using multivariable regression models. All statistical tests were two-sided. RESULTS: The mutation was carried by 30 patients (5.7%). Compared with noncarriers, BRCA2 999del5 mutation carriers had a lower mean age at diagnosis (69.0 years versus 74.0 years; P = .002), more advanced tumor stage (stages 3 or 4, 79.3% versus 38.6%; P < .001), higher tumor grade (grades G3-4, 84.0% versus 52.7%, P = .007), and shorter median survival time (2.1 years, 95% CI = 1.4 to 3.6 years, versus 12.4 years, 95% CI = 9.9 to 19.7 years). Carrying the BRCA2 999del5 mutation was also associated with an increased risk of dying from prostate cancer (adjusting for year of diagnosis and birth, HR = 3.42, 95% CI = 2.12 to 5.51); the association remained after adjustment for stage and grade (HR = 2.35, 95% CI = 1.08 to 5.11). The prognosis of BRCA2 999del5 mutation carriers was not associated with period of diagnosis or with relatedness to breast cancer probands. CONCLUSIONS: The Icelandic BRCA2 999del5 founder mutation was strongly associated with rapidly progressing lethal prostate cancer.

Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000.

BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5. METHODS: Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided. RESULTS: Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out. CONCLUSIONS: The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.

Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: a population-based case-control study in the five Nordic countries.

The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960-1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

Associations between three types of maternal bacterial infection and risk of leukemia in the offspring.

A case-control study was nested within two maternity cohorts with a total of 7 million years of follow-up for assessment of the role of bacterial infections in childhood leukemia. Offspring of 550,000 mothers in Finland and Iceland were combined to form a joint cohort that was followed for cancer up to age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from population registers. First-trimester serum samples were retrieved from mothers of 341 acute lymphoblastic leukemia cases and 61 other leukemia cases and from 1,212 control mothers. Sera were tested for antibodies to the genus Chlamydia, Helicobacter pylori, and Mycoplasma pneumoniae. Odds ratios and 95% confidence intervals, adjusted for sibship size, were calculated as estimates of relative risk. M. pneumoniae immunoglobulin M appeared to be associated with increased risk (odds ratio (OR) = 1.6), but the association lost statistical significance when the specificity of the immunoglobulin M was considered (OR = 1.5, 95% confidence interval: 0.9, 2.4). In Iceland, H. pylori immunoglobulin G was associated with increased risk of childhood leukemia in offspring (OR = 2.8, 95% confidence interval: 1.1, 6.9). Since H. pylori immunoglobulin G indicates chronic carriage of the microorganism, early colonization of the offspring probably differs between Iceland and Finland, two affluent countries.

Breast cancer risk factors and age at diagnosis: an Icelandic cohort study.

An increasing number of studies indicates that the strength and even direction of association between breast cancer and established risk factors differ according to the woman's age when she develops the disease. This was studied in the setting of a population based cancer registry using a databank with information on age at menarche, parity, age at first birth, oral contraceptive (OC) use, lactation, height and weight. From a cohort of 80.219 women attending population-based cervical and breast cancer screening in Iceland, 1120 cases were identified, aged 26-90 years at diagnosis and 10,537 controls, individually matched to the cases on birth year and age when attending. Information given at last visit before diagnosis was used in the analysis, applying conditional logistic regression. Odds ratios and statistical strength of relationships varied according to age at diagnosis for age at first birth, number of births, duration of lactation, height and weight. The decreased risk associated with young age at first birth and increasing duration of breast feeding became less pronounced with advancing age at diagnosis. A reduced risk associated with an increasing number of births was not detected in women diagnosed under the age of 40. An increased risk associated with giving first birth after 30 years of age was mainly detected in women who had only given 1 birth and were diagnosed under the age of 40 (OR = 7.06 95% CI = 2.16-23.01). A positive association with height and especially with weight was confined to women diagnosed after the age of 55. The results confirm that age at diagnosis should be taken into account when studying the effects of breast cancer risk factors.

Risk factors for malignant melanoma in an Icelandic population sample.

OBJECTIVES: To describe the constitutional risk factors for malignant melanoma and exposure to sunlight in a population sample in Iceland. METHODS: Information on various risk factors for malignant melanoma was collected through mailed questionnaires sent to a random sample of the Icelandic population. The information collected was the first phase of a prospective study on malignant melanoma among aircrew members as compared to a population sample. RESULTS: The overall participation rate was about 50%. Seven percent of women and six percent of men had red hair color. Blue or green eye color was reported among 89% of women and 87% of men. Sixteen percent of women aged 20 to 39 had used sun beds more than 100 times during their lifetime, while the corresponding figure was 12% for men of the same age. Younger age groups had more sunny vacations than the older age groups. The frequency of sunburn differed in the groups with reported different skin types according to Fitzpatrick classification. CONCLUSION: The high prevalence of sun bed usage among young women is concurrent with the increased incidence of malignant melanoma among young women registered in the nationwide cancer registry. Young people have more often used sun beds and taken sunny vacation than the older, indicating a changed behavior in the population.

Monoclonal gammopathy in Iceland: a population-based registry and follow-up.

The term monoclonal gammopathy (MG) signifies the benign or malignant clonal growth of B lymphocytes. In the present study, monoclonal gammopathy of unknown significance (MGUS) was defined as those patients with no identified haematological malignancy. A database was constructed of all 713 MG patients in Iceland between 1976 and 1997 and compared with the Icelandic Cancer Registry. The age-standardized incidence per 100 000 of MG was 10.3 for males and 8.6 for females, calculated for the whole period, rising steadily from 5.8 (men) and 4.9 (women) during the 5-year period 1976-80 to 14.7 (men) and 12.5 (women) during the last 5 year period. Age-standardized incidence rates were very low for subjects under 50 years of age, then increased with age from 11 and 17 per 100 000 at 50-54, to 169 and 119 per 100 000 at age 80-84, for men and women respectively. No association was detected between MG and non-haematological malignancies, neither retrospectively nor prospectively. Haematological malignancy was diagnosed in 209 (29.3%) cases before the recorded finding of MG or within the same calendar year, leaving 504 (70.7%) patients diagnosed with MGUS. Of these, 51 (10%) progressed to multiple myeloma or Waldenström's macroglobulinaemia after a mean interval of 3.8 years; mean follow-up was 7.4 years, median 6 years. The most common immunoglobulin (Ig) class was IgG (55%), followed by IgM (32%) and IgA (13%). MGUS was a highly significant risk factor for developing haematological malignancies and the risk was significantly greater for MG of the IgA class compared with either IgG or IgM.

Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring.

A critical role for infection in the etiology of childhood leukemia has repeatedly been suggested. The authors undertook a case-control study nested within national maternity cohorts with altogether 7 million years of follow-up to assess the relative role of three maternal herpesvirus infections in childhood acute lymphoblastic leukemia (ALL). Offspring of 550,000 mothers in Finland and Iceland formed the joint study cohort that was followed up for cancer in the offspring before age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from national population registers. First-trimester sera were retrieved from mothers of 342 ALL and 61 other leukemia cases and from 1,216 control mothers and were tested for antibodies to cytomegalovirus, Epstein-Barr virus (EBV), and human herpesvirus 6. Serum EBV DNA was also analyzed. Conditional logistic regression-based estimates of relative risk (odds ratio) adjusted for birth order and sibship size, and population attributable fractions, were calculated. Only EBV immunoglobulin M positivity in EBV-immunoglobulin-G-positive mothers was associated with a highly significant increased risk of ALL in the offspring (adjusted odds ratio = 2.9, 95% confidence interval: 1.5, 5.8). Results indicate that reactivation of maternal EBV infection is probably associated with childhood ALL.

Segregation analysis of 389 Icelandic pedigrees with Breast and prostate cancer.

Breast cancer and prostate cancer are the most commonly occurring cancers in females and males, respectively. The objective of this project was to test the hypothesis that breast cancer in females and prostate cancer in males represent homologous cancers that may be controlled by one or more common unidentified genes that may explain some of the observed familial aggregation. We modeled the transmission of a breast-prostate cancer phenotype in 389 pedigrees ascertained through a breast cancer proband drawn from the Icelandic Cancer Registry. Assuming that age at diagnosis of this combined phenotype followed a logistic distribution, segregation analyses were performed to evaluate residual parental effects, a sibship covariate, and a dichotomous cohort effect. The most parsimonious model was a Mendelian codominant model, which could partly explain the familial aggregation of both cancers. Inheritance of a putative high-risk allele (A) predicted gender-specific mean ages of onset for females as 53.8 years, 59.7 years, and 65.6 years for the putative AA, AB, and BB genotypes, respectively. Similarly, the predicted means were 73.7 years, 75.6 years, and 78.3 years, respectively, among males. Under this codominant model, the lifetime risk of a woman being affected was 19% by age 80 years. This implies that when prostate cancer among male relatives of breast cancer probands (unselected for family history or early-onset disease) is considered a pleiotrophic effect of the same gene that increases the risk for breast cancer, women are predicted to have a less than 1 in 5 risk of developing breast cancer when they carry the putative high-risk allele. However, this is a higher risk than in the general Icelandic population. Our results suggest that BRCA2 mutations alone are inadequate to explain all of the excess clustering of prostate cancer cases in families of breast cancer probands, and that additional genes conferring excess risk to both breast and prostate cancer may exist in this population.

Mortality from cancer and other causes among male airline cockpit crew in Europe.

Airline pilots and flight engineers are exposed to ionizing radiation of cosmic origin and other occupational and life-style factors that may influence their health status and mortality. In a cohort study in 9 European countries we studied the mortality of this occupational group. Cockpit crew cohorts were identified and followed-up in Denmark, Finland, Germany, Great Britain, Greece, Iceland, Italy, Norway and Sweden, including a total of 28,000 persons. Observed and expected deaths for the period 1960-97 were compared based on national mortality rates. The influence of period and duration of employment was analyzed in stratified and Poisson regression analyses. The study comprised 547,564 person-years at risk, and 2,244 deaths were recorded in male cockpit crew (standardized mortality ratio [SMR] = 0.64, 95% confidence interval [CI] = 0.61-0.67). Overall cancer mortality was decreased (SMR = 0.68; 95% CI = 0.63-0.74). We found an increased mortality from malignant melanoma (SMR = 1.78, 95% CI = 1.15-2.67) and a reduced mortality from lung cancer (SMR = 0.53, 95% CI = 0.44-0.62). No consistent association between employment period or duration and cancer mortality was observed. A low cardiovascular mortality and an increased mortality caused by aviation accidents were noted. Our study shows that cockpit crew have a low overall mortality. The results are consistent with previous reports of an increased risk of malignant melanoma in airline pilots. Occupational risk factors apart from aircraft accidents seem to be of limited influence with regard to the mortality of cockpit crew in Europe.