Decreasing incidence of cancer after liver transplantation-A Nordic population-based study over 3 decades.

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. METHODS: We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. RESULTS: Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERß)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. CONCLUSIONS: Our findings provide support for ERß and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

BACKGROUND: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). METHODS: During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. RESULTS: Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). CONCLUSION: These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.

Metabolic syndrome and rare gynecological cancers in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. MATERIALS AND METHODS: The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. RESULTS: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). CONCLUSION: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Familial risks in nervous system tumours: joint Nordic study.

BACKGROUND: Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours. METHODS: Data from five Nordic countries were used to analyse familial risks of nervous system tumours. Standardised incidence ratios (SIRs) were calculated for offspring of affected relatives compared with offspring of non-affected relatives. RESULTS: The total number of patients with nervous system tumour was 63 307, of whom 32 347 belonged to the offspring generation. Of 851 familial patients (2.6%) in the offspring generation, 42 (4.7%) belonged to the families of a parent and at least two siblings affected. The SIR of brain tumours was 1.7 in offspring of affected parents; it was 2.0 in siblings and 9.4 in families with a parent and sibling affected. For spinal tumours, the SIRs were much higher for offspring of early onset tumours, 14.0 for offspring of affected parents and 22.7 for siblings. The SIRs for peripheral nerve tumours were 16.3 in offspring of affected parents, 27.7 in siblings and 943.9 in multiplex families. CONCLUSION: The results of this population-based study on medically diagnosed tumours show site-, proband- and age-specific risks for familial tumours, with implications for clinical genetic counselling and identification of the underlying genes.

Association between serum 25(OH)D and death from prostate cancer.

Based on observations that for certain cancers, mortality varies according to sun exposure, vitamin D has been proposed to influence on disease progression. This study aims to investigate whether serum levels of 25(OH)D are associated with prognosis in patients with prostate cancer. In total, 160 patients with a serum sample in the JANUS serum bank were included. For 123 patients a pre-treatment serum sample was taken, whereas 37 of the patients had received hormone therapy prior to the blood collection. The serum level of 25(OH)D was classified as low (<50 nmol l(-1)), medium (50-80 nmol l(-1)) or high (>80 nmol l(-1)). A Cox proportional hazard regression model was used to assess the association between serum 25(OH)D and cancer mortality. During follow-up, 61 deaths occurred, of whom 52 died of prostate cancer. The median time of follow-up was 44.0 months (range, 1.2-154.6). Serum 25(OH)D at medium or high levels were significantly related to better prognosis (RR 0.33; 95% CI 0.14-0.77, RR 0.16; 95% CI 0.05-0.43) compared with the low level. Analysis restricted to patients receiving hormone therapy gave a stronger association. The serum level of 25(OH)D may be involved in disease progression and is a potential marker of prognosis in patients with prostate cancer.

Birth and parental characteristics and risk of neuroblastoma in a population-based Norwegian cohort study.

In this population-based Norwegian cohort study (2.1 million children), the impact of birth and parental characteristics on the risk of neuroblastoma (178 cases) was evaluated. In children below the age of 18 months, there was an increased neuroblastoma risk among those with congenital malformations and suggestion of increased risk when the mother had pre-eclampsia.

Response to Intravenous Glucose-Tolerance Test and Risk of Cancer: A Long-Term Prospective Cohort Study.

BACKGROUND: Impaired glucose regulation, measured with an oral glucose-tolerance test, has been associated with the risk of cancer. Here, we explored whether the response to an intravenous glucose-tolerance test (IVGTT) is associated with the risk of cancer. METHODS: A cohort of 945 healthy men, aged 40-59years in 1972-75, was followed for 40years. An IVGTT was performed at baseline. Blood samples for glucose determinations were drawn immediately before glucose injection and thereafter every 10min for 1h. Associations were assessed with incidence rate ratios (IRR) and Cox models. FINDINGS: Cancer incidence was higher among men with 10-min glucose levels below the median than in men with levels above the median (IRR: 1.5, 95% CI: 1.2-1.9). This association remained significant after adjusting for relevant confounders (HR: 1.6, 95% CI: 1.3-2.1) and when excluding the first 10years of follow-up to minimize the possibility of reverse causality (HR: 1.5, 95% CI: 1.2-2.0). INTERPRETATION: Healthy middle-aged males that responded to an intravenous glucose injection with rapid glucose elimination during the first phase had an elevated risk of cancer during 40years of follow-up. First phase response to a glucose load might be related to cancer development.

Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon.

BACKGROUND: For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development can be traced back to the first half of this century. PURPOSE: By evaluating data from six countries with long periods of cancer registration (Denmark, Norway, Sweden, the former German Democratic Republic [East Germany], Finland, and Poland), we sought to determine whether the increase in testicular cancer risk follows a birth cohort pattern and, if so, to quantify and compare any birth cohort effects. METHODS: A total of 30,908 incident cases of testicular cancer, diagnosed from 1945 through 1989 in men who were 20-84 years of age, were identified in population-based cancer registries in the six countries. In addition to performing simple trend analyses, we fitted several Poisson regression models (with the explanatory variables age, time period [calendar time], and birth cohort) to the data. Individual models were estimated by the maximum likelihood method. RESULTS: The age-standardized incidence of testicular cancer was found to vary among the six populations and, on the basis of total registration data, increased annually at rates ranging from 2.3% (in Sweden) to 5.2% (in East Germany). A comparison of several regression models indicated that birth cohort was a stronger determinant of testicular cancer risk than was calendar time for all six populations. Within each population, little variation in testicular cancer risk was observed for men born between 1880 and 1920; thereafter, the risk began to increase. Among men born in Denmark, Norway, and Sweden between 1930 and 1945 (the period encompassing the Second World War), the increasing trend in risk was interrupted (i.e., a leveling in risk occurred). After 1945, an uninterrupted increase in risk was observed for all six populations. With men born around 1905 as the reference group, the relative risk of testicular cancer for those born around 1965 varied from 3.9 (95% confidence interval [CI] = 2.7-5.6) in Sweden to 11.4 (95% CI = 8.3-15.5) in East Germany. CONCLUSIONS AND IMPLICATIONS: The increasing trend in testicular cancer risk observed for these six populations follows a birth cohort pattern. This distinct risk pattern provides a framework for the identification of specific etiologic factors.

Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.

BACKGROUND: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. METHODS: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. RESULTS: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. CONCLUSIONS: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.

Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and histology: a joint study from five Nordic countries.

We aimed to estimate stratified absolute (cumulative) and relative (standardized incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who were diagnosed between 1955 and 2010 in five European countries was followed for cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6, 95% confidence interval (CI)=1.2-1.9) over the general population risk. NHL risk among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5; lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his son). When there were ⩾2 NHL patients diagnosed in a family, the lifetime NHL risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a 3.1-12.9% lifetime risk of NHL. Family history of most of the histological subtypes of NHL increased the risk of concordant and some discordant subtypes. Familial risk did not significantly change by age at diagnosis of NHL in relatives. Familial risk of NHL was not limited to early onset cases.

Weak associations between sociodemographic factors and breast cancer: possible effects of early detection.

Differences in incidence and survival of breast cancer have been observed to vary with regard to sociodemographic factors. This might be related to variation in frequency of doctor consultation and in time of diagnosis, since sociodemographic factors appear to influence the individual's attention to cancer symptoms and susceptibility to participate in screening programmes. This study aimed to examine the variation in breast cancer incidence and case fatality in sociodemographic groups in Norway, and to discuss whether any variation can result from temporal variation in detection time. The study included 589 521 women with information on residential history, childbearing pattern, educational level and occupational physical activity. Analyses were conducted using Poisson and Cox regression models. Although all the associations were weak, breast cancer incidence was associated with residence in urban areas, high age at first childbirth and high level of education. The urban women also tended to have better survival compared with the rural women. Childlessness was associated with high incidence and high case fatality. A high educational level was associated with the lowest case fatality. This study may emphasize the importance of discussing potential effects of early cancer detection. This is particularly important in epidemiological studies revealing weak associations between sociodemographic factors and breast cancer. Mortality rates may be less influenced by problems associated with early detection and, thus, analyses of breast cancer-specific mortality could give additional information.

Symptoms and referral of women with epithelial ovarian tumors.

OBJECTIVE: To study referral to hospital units and the clinical characteristics of women with epithelial ovarian tumors in a prospective, population-based study. METHODS: Clinical information on all women diagnosed with epithelial invasive (n=486) and borderline ovarian tumors (n=137) in Norway during 2002 was derived from notifications to the Cancer Registry of Norway and medical, surgical and histopathological records. RESULTS: Sixty-one percent of women with invasive ovarian tumors were initially referred to gynecology units. The 38% of women referred to surgical and medical units were more likely to have symptoms as 'bowel irregularity', 'pain outside the abdominal cavity', 'persisting fatigue' and 'respiratory difficulties'. These women were older, had lower performance status and had a delay in treatment of 20 and 24 days respectively compared to 11 at gynecology units. CONCLUSION: Greater awareness of the symptoms of ovarian cancer might lead to earlier diagnosis and treatment and thus possibly improve survival.

Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. The protein truncation test (PTT), fragment length and heteroduplex analyses of large (0.8-1.2 kb) cDNA fragments were used. In total, 67 of 82 (82%) of the disease-causing alleles were characterized. Thirty-seven unique mutations were detected of which 25 have not previously been reported. The mutations had five different consequences for the ATM transcript: mutations affecting splicing (43%); frameshift mutations (32%); nonsense mutations (16%); small in-frame deletions (5%); and one double substitution (3%). In 28 of the probands mutations were found in both alleles, in 11 of the probands only one mutated allele was detected, and no mutations were detected in two Finnish probands. One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygote with at least one identified allele. Ten alleles were found more than once; one Norwegian founder mutation constituted 57% of the Norwegian alleles. Several sequence variants were identified, none of them likely to be disease-causing. Some of them even involved partial skipping of exons, leading to subsequent truncation of the ATM protein.

Quality of prostate cancer data in the cancer registry of Norway.

Completeness of reporting and internal validity of the coding of prostate cancer in the Cancer Registry (CR) in Norway were examined. Data were matched and evaluated against diagnostic indices at eight selected hospitals in the country and against death certificates from Statistics Norway. Validity control was based on detailed re-analysis of an approximately 1% sample of the registered data during the period 1957-1986. The deficiency in reporting of prostate cancer was less than 1%. The grave deficiencies in hospital patient registers were considered to be of non-systematic nature and should, therefore, not impair the reliability of our investigation of incompleteness. The validity control revealed errors in 0.5% of the data elements, or, illustrated differently, 6% of the patient files had an error, of importance or not, in one of the data elements. One false positive registration was found among 298 controlled patient files (0.3%).

Cancer of the prostate in Norway 1957-1991--a descriptive study.

The incidence and mortality of prostate cancer from 1957 to 1991 were studied in the Cancer Registry of Norway. The age-adjusted incidence rate increased from 26.3 to 46.6 per 100,000 person-years during the period, and more than 2000 cases are now registered yearly. The increase tends to be higher in the younger age groups, 50-59 years, and among the oldest, 90+ years. An increase was also found in cause-specific mortality, signifying a real increase in incidence over time. There is a slight urban dominance in incidence of prostate cancer. Autopsy findings account for less than 1.7% of the total. The histo- and cytological verification rate reached 94% in 1987-1991 and the percentage of localised cases was 68.4%. The median age at diagnosis in 1987-1991 was 75.1 years. Data on stage at time of diagnosis, histological differentiation and survival, reflect a small influence of earlier diagnosis. Model analysis revealed no particular birth cohort effect, either on incidence or on mortality.

Trends in incidence of testicular cancer in Norway 1955-1992.

The aim of this study was to explore the incidence of testicular cancer (TC) in Norway, and thereby to increase the understanding of aetiological factors. From 1995 to 1992, a total number of 3927 TC cases were recorded in Norway, of which 51% were seminomas, 45% non-seminomas and 4% other and unspecified types. The age-standardised incidence rate increased from 2.7 to 8.5 per 100,000. The age-specific incidence rate increased in all age groups, but was most marked in the younger population. The significance of birth cohort as a risk factor for development of TC was confirmed. The incidence by birth cohorts from 1916 to 1970 showed an increase by later birth cohorts during the whole period, with the exception of a marked fall for the cohort born during the Second World War. The largest increase occurred after the war. We conclude that environmental factors acting very early in life are of significance in the development of TC.

Risk of a second germ cell cancer after treatment of a primary germ cell cancer in 2201 Norwegian male patients.

The aim of this study was to evaluate the risk of developing a second germ cell cancer (SGCC) among male patients with a primary germ cell cancer (PGCC). SGCCs, all metachronous, developed in 60 out of 2201 males treated for a PGCC at the Norwegian Radium Hospital in Oslo from 1953 to 1990. Further, 8 patients had synchronous germ cell cancers. The relative risk (RR) of developing an SGCC was 27.6 (95% confidence interval (CI) 21.1-35.6), and the cumulative risk at 15 years of follow-up 3.9% (95% CI 2.8-5.0%). In patients with primary non-seminoma, the cumulative risk of an SGCC at 15 years of follow-up was 5.0% and in patients with primary seminoma 3.4%. Patients less than 30 years of age had a higher cumulative risk of 7.8% compared to 2.1% in older patients at 15 years of follow-up. The RR of an SGCC, however, was equal in patients with primary seminoma and in patients with primary non-seminoma. If the interval between PGCC and SGCC was < 5 years, the PGCC was most often followed by an SGCC of same histological type. Treatment applied for the PGCC did not seem to be of significant importance for the development of SGCC. In conclusion, patients with PGCC have high RR of developing an SGCC and age group < 30 years display an especially high cumulative risk.

Risk of subsequent non-germ cell cancer after treatment of germ cell cancer in 2006 Norwegian male patients.

The aim of this study was to evaluate the risk of subsequent non-germ cell cancer (SNGC) among men with germ cell cancer and the significance of radiotherapy and chemotherapy as risk factors. The study group consisted of 2006 male patients treated for germ cell cancer at the Norwegian Radium Hospital from 1952 to 1990 with a mean follow-up of 12.5 years. A group of 1194 patients had received radiotherapy only, 346 patients chemotherapy only (mainly cisplatin-based), 277 patients both radiotherapy and chemotherapy (mainly cyclophosphaoffe and doxorubicin-based), and 189 patients no cytotoxic treatment. A total number of 153 SNGCs were diagnosed after a mean interval of 15.9 years. The RR was 1.65 (95% confidence interval (CI), 1.4-1.9), and the mean cumulative risk after 15 years 7.8% (95% CI, 6.2-9.5%). Significantly elevated RRs were found for gastrointestinal cancer combined, cancer of stomach, liver and biliary system, lung, melanoma, bladder and sarcoma. Significantly elevated RRs were found in patients who had received radiotherapy (with or without chemotherapy), and the trend increased with very long follow-up. Patients given both radiotherapy and chemotherapy experienced the highest risk (RR = 3.54; 95% CI, 2.0-5.8), probably due to a high cumulative dose of cytotoxic treatment. Modern chemotherapy did not seem to increase the risk of SNGC, although this study's size and follow-up period did not allow definite conclusions as regards this risk factor.

Death of a husband or marital divorce related to risk of breast cancer in middle-aged women. A nested case-control study among Norwegian women born 1935-1954.

A topic of general interest is whether important life changes may play a role in the onset of cancer. The hypothesis of this study was that death of a husband or marital divorce, is associated with an increased risk of breast cancer. The study included 4491 incident breast cancer cases and 44,910 controls, matched on age, in a population-based nested case-control study, among Norwegian women born between 1935 and 1954. The risk of breast cancer among widowed compared to married women showed an odds ratio (OR) of 1.13 [95% confidence interval (CI) 0.94-1.36], after adjusting for age at first birth and parity. For divorced women the analogous OR was 0.83 (95% CI 0.75-0.92), after adjusting for age at first birth, parity and place of residence. Thus, the results did not show any clear evidence that death of a husband or marital divorce was associated with an increased risk of breast cancer.