Eystein Glattre

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

BACKGROUND Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. METHODS To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. RESULTS After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. CONCLUSIONS HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.

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.

Risk of cancer among offspring of childhood-cancer survivors

BACKGROUND Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain. METHODS Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated. RESULTS Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0). CONCLUSIONS There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.

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.

Norwegian case-control study testing the hypothesis that seafood increases the risk of thyroid cancer

The hypothesis that consumption of seafood increases the risk of thyroid cancer has been tested by means of a matched case-control study. Linking the file of the National Health Screening Service (NHSS) containing dietary information about 60,000 Norwegians with the 1955–89 thyroid-cancer file of the Cancer Registry, by means of the 11-digit person-number, resulted in 92 cases—each of whom was matched with five controls with regard to age, gender, and place of residence. Forty-eight cases had answered questions on diet before diagnosis; 44 did so after diagnosis. Exposure data on seafood and seafood-related vitamins were recovered from the NHSS files for all 552 subjects. Odds ratios (OR) were computed by means of conditional logistic regression analysis. Univariate analysis of the 48 sets in which the case had answered the dietary questionnaire prior to the thyroid cancer diagnosis, as well as of all 92 sets, indicate that regular users of cod-liver oil, fish liver, or fish sandwich-spread run a higher risk of thyroid cancer than irregular and nonusers, and people eating more fish dinners per week also run a higher risk of thyroid cancer. Stepwise regression analysis corroborates the study hypothesis by showing that these two seafood variables increase the risk of thyroid cancer significantly. On the other hand, the results of a simultaneous regression analysis of these two seafood variables and a dietary vitamin-D index-variable tend to reduce the tenability of the above-mentioned conclusion since none of the OR estimates (all greater than one) reached significance in this part of the statistical analysis.

Longchain serum fatty acids and risk of thyroid cancer: A population-based case-control study in Norway

Epidemiologic studies have shown an association between seafood consumption and risk of thyroid cancer. Fish meals increase the serum concentrations of the longchain fatty acids, eicosapentaenoic acid (20∶5,n-3) (EPA) and docosahexaenoic acid (22∶6,n-3) (DHA), for days. The hypothesis that serum concentrations of fatty acids may be associated with thyroid cancer risk therefore was tested in a population-based case-control study with 74 cases and 221 matched controls. Seventy-three cases with sera in the Norwegian serum bank (JANUS) were identified in the Norwegian Cancer Registry and matched with three controls, also in JANUS, on age, gender, place of residence, and time of blood sampling. Each case was matched with two controls. Serum concentrations of 11 longchain fatty acids were determined blindly by gas chromatography for all subjects. Controls were divided into three groups with increasing serum fatty acid concentrations, and odds ratios between cases and controls were estimated relative to the group with lowest serum level by univariate and multivariate analyses. The main finding was a significant inverse relation between the sum of arachidonic acid (20∶4,n-6) (AA) and DHA serum concentrations and thyroid cancer risk. The significance of this association was weakened when the analyses were restricted to the papillary type of thyroid carcinoma. It was of the same order of magnitude whether the period between blood sampling and diagnosis was greater than eight years, or eight or less years. High EPA/AA ratio, indicating consumption of fish fat, was not associated significantly with increased thyroid-cancer risk. These data indicate that the association between seafood ingestion and increased thyroid-cancer risk may not be caused by the marine fatty acids.

Familial risk in head and neck squamous cell carcinoma diagnosed before the age of 45: a population-based study.

This population-based study analyses familial risk as a factor in the development of head and neck squamous cell carcinoma before the age of 45. Two different designs were used: (1) estimation of standardised incidence ratios (SIRs) for cancer among first-degree relatives of 127 young head and neck cancer probands; and (2) estimation of odds ratios (ORs) for developing head and neck cancer associated with cancer in a first-degree relative. SIRs of cancer of the respiratory and upper digestive tract (lungs, oesophagus, and smoking-related head and neck sites [RUDT]) for first-degree relatives were 4.3 (95% confidence intervals or 95% CI of 1.6-9.5) for female patients, 1.0 (95% CI = 0.3-2.6) for male patients and 1.9 (95% CI = 0.9-3.5) for both sexes combined. ORs for head and neck cancer before the age of 45, in association with cancer of RUDT in a first-degree relative were 5.0 (95% CI = 1.4-17.3) for women, 1.1 (95% CI = 0.3-3.3) for men, and 2.0 (95% CI = 0.9-4.4) for both sexes combined. Hence, when analysing both sexes combined, our familial risk estimates for head and neck cancer showed non-significant increases. An explanation for the unexpected sex asymmetry in familial risk could be an interaction between inherent cancer susceptibility and a female biological characteristic. Alternatively, it could be artefacts caused by differences in familial smoking habits.

SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK IN NORWAY, 1953-92 : AN EPIDEMIOLOGIC STUDY OF A LOW-RISK POPULATION

Trends in incidence, five-year relative survival, and mortality among patients in Norway with squamous cell carcinoma of the oral sites, oro-/hypopharynx, and larynx were studied for the period 1953-92. Throughout the first part of the study period, age-adjusted incidence rates (AAIR) of oral cancer remained stable in both genders. Since the end of the 1960s, AAIRs increased by 13 percent per five-year period in males and 12 percent in females. The figures suggest increased male incidence rates of oral cancer in younger age groups. During the same period, AAIRs of cancers of the oro-/hypopharynx in males increased by 19 percent per five-year period. The AAIRs of laryngeal cancer increased steadily from 1953-92 among both males and females by 17 percent and 21 percent per five-year period, respectively. For all sites, changes in AAIRs for males were greater in rural than in urban areas. No improvement in detection of disease at a localized stage was observed for either gender. There are indications of improvements in the five-year relative survival rates for oral and pharyngeal cancer in both genders. For all sites, relative survival was better in younger than in older patients. Only in the case of pharyngeal cancer in males was an increase in disease-specific mortality rates positive for a time trend.

Late mortality among five-year survivors of cancer in childhood and adolescence.

The present study was aimed at assessing differences between the Nordic countries, if any, in late mortality among five-year survivors of childhood cancer. All cases diagnosed before the age of 20 years, between 1960 and 1989, were collected from all Nordic cancer registries. In total, 13 689 patients were identified as five-year survivors and during the extended follow-up 12.3% of them died. Mortality was analysed by decade of diagnosis, for all sites, and for leukaemia, Hodgkins lymphoma, and central nervous system tumours separately. Analyses were done within a Cox proportional hazards regression framework with adjustments made for gender and age at diagnosis. Hazard ratios were calculated in relation to a weighted Nordic mean based on the proportion of five-year survivors in each country. Overall late mortality was significantly higher in Denmark and Finland than in Norway and Sweden. This could not be explained by inverse differences in five-year survival. The differences diminished over time and had disappeared in the last period. The pattern was similar for both genders. The disappearance of the differences was most probably the effect of a closer collaboration between Nordic paediatric oncologists with development and implementation of common protocols for treatment of childhood cancers in all countries.

Effect of long-term storage on the concentration of albumin and free fatty acids in human sera

Stored sera from healthy persons can be used to study relationships between blood variables at the time of sampling and disease appearing several years later but storage may influence the variables. In this work we measured the concentration of albumin and free fatty acids (FFA) in samples from the JANUS serum bank of Norway. Sera from blood donors and persons participating in health screening programs have been added to the bank since 1973. The concentration of albumin and FFA was measured in 443 JANUS bank sera. The material was divided into quartiles according to the length of storage: < 3 years (n = 110), 3-6 years (n = 110), 6-12 years (n = 115) and > 12 years (n = 108). Albumin was measured colorometrically using the bromcresol green method and FFA was determined enzymatically. The serum albumin concentrations (mean - SEM) in the four groups were 55.8 - 0.6, 56.2 - 0.5, 59.9 - 0.6 and 59.5 - 0.6 g/L. The values of groups 3 and 4 were significantly higher than those of groups 1 and 2 (p< 0.001). The serum FFA concentrations in the four groups were 0.56 - 0.03, 0.64 - 0.03, 0.77 - 0.03 and 0.85 - 0.04 mmol/L, i.e. a significant storage effect. The Scheffe´multiple comparison test showed that FFA values in groups 3 and 4 were significantly higher than those in groups 1 and 2 (p< 0.001 for group 4 vs. 1 and 2, and 3 vs. 1; p< 0.04 for group 3 vs. 2). Serum FFA and albumin levels were positively associated (r = 0.489, p< 0.001). Using linear regression analysis, it was estimated that serum albumin values increased by 0.28 g/L per year (i.e. 0.5%) and FFA by 0.02 mmol/L (i.e. 3.8%). Thus, measured by standard methods, serum FFA and albumin could increase in response to several years of storage at ° - 25 C. It is suggested that the storage time dependent increase in FFA is due to FFA liberation from lipoprotein triglycerides, whereas the apparent increase in albumin concentration possibly could be attributed to an unfolding of the protein, allowing more bromcresol green to be bound.