Abstract: OBJECTIVE: In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. MATERIAL AND METHODS: We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995-1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. RESULTS: Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60-2.03] in women and 0.94 [95% CI 0.53-1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17-7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68-1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35-3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. CONCLUSIONS: C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.

Abstract: BACKGROUND: Long-term illness and work incapacity in young adulthood has consequences for both the individual and for society. The purpose of the study was to investigate the association between adolescent health and receipt of long-term sickness and disability benefits for young adults in their twenties. MATERIAL AND METHOD: An adolescent population of 8949 school students (aged 13-21 years) assessed their own health in the Young-HUNT1 Study (1995-1997). Health was measured by means of a questionnaire enquiring about chronic somatic illnesses, somatic symptoms, symptoms of anxiety and depression, sleep disturbance, poor concentration, self-reported health and smoking, and by measuring height and weight. Information about receipt of long-term benefits was retrieved from the FD-Trygd registry for the period 1998-2008 and defined as receipt of sickness benefit (>180 days/year), medical/vocational rehabilitation benefit and disability pension in the age group 20-29 years. We investigated the relationship between adolescent health and long-term social insurance benefits with logistic regression, adjusted for sex, age, follow-up time, mother's education and family composition. Siblings with different exposure and outcome were investigated to adjust for all familial factors shared by siblings. RESULTS: Each of the health measures was associated with an increased risk of long-term benefit. For example, adolescents who reported one or more somatic illnesses or poor concentration had a 5.4 and 3.4 percentage point higher risk, respectively, of receiving long-term benefits at the age of 20-29 years than adolescents who did not report somatic illness or poor concentration. Moreover the risk increased with an increase in the number of health problems. Sibling analyses supported these associations. INTERPRETATION: Health in adolescence is an indicator of increased vulnerability in the transition to the labour market. Preventing health selection during this transition should be a priority for welfare policy.

Abstract: The incidence of forearm fractures for men and women >/=40 years in Central Norway was high during the period 1999-2012. A decline in fractures was observed only among women over 50 years. A seasonal variation with highest incidence in the winter months was found among women. PURPOSE: The aim of this study was to examine the incidence of forearm fractures in Central Norway in men and women 40 years and older from 1999 to 2012 and assess time trends as well as seasonal variations. METHODS: Data is from the fracture registry in Nord-Trondelag, including all forearm fractures in persons >/=40 sustained from 1999 to 2012. Annual incidence of forearm fractures were calculated and tested for trends. Variations in the occurrence of fractures were explored by comparing proportion of fractures by month and seasons. RESULTS: The study population consisted of 4003 subjects (77.1% women). The total number of fractures were 4240. There was an increase in fractures for women with increasing age, steepest, a three-fold increase between age group 40-50 and the age group 50-60. Among men, this pattern was not observed as incidences did not change with increasing age. The age-standardized incidence rate for all fractures among women >/=50 ranged from 82 fractures per 1000 (95% CI 71-94) to 100 (88-114) and among men from 19 (14-27) to 31 (24-39). Restricting the analysis to the first fracture sustained during the observed period, women >/=50 years showed a reduction in fractures of 1.30% per year (95% CI 0.01%: 2.56%,) and 12.18% per 10 years (3.61%: 19.98%). For all women, there was a trend towards a decline of 0.73% per year (-2.29%: 0.85%), although not significant. For men, there was a trend towards an increase in fractures of 1.66% per year (-0.11%: 3.45%). The occurrence of fractures among women varied by season of the year, with higher fracture rates in the winter months. CONCLUSIONS: The incidence rate of forearm fractures in Central Norway was high. However, a small decline in the incidence of the first fracture among women older than 50 years was observed. Fractures were more often sustained during winter months among women.

Abstract: BACKGROUND: The impact of body mass index (BMI; kg/m(2)) and waist circumference (WC) on mortality in elderly individuals is controversial and previous research has largely focused on obesity. METHODS: With special attention to the lower BMI categories, associations between BMI and both total and cause-specific mortality were explored in 7604 men and 9107 women aged >/= 65 years who participated in the Tromso Study (1994-1995) or the North-Trondelag Health Study (1995-1997). A Cox proportional hazards model adjusted for age, marital status, education and smoking was used to estimate HRs for mortality in different BMI categories using the BMI range of 25-27.5 as a reference. The impact of each 2.5 kg/m(2) difference in BMI on mortality in individuals with BMI < 25.0 and BMI >/= 25.0 was also explored. Furthermore, the relations between WC and mortality were assessed. RESULTS: We identified 7474 deaths during a mean follow-up of 9.3 years. The lowest mortality was found in the BMI range 25-29.9 and 25-32.4 in men and women, respectively. Mortality was increased in all BMI categories below 25 and was moderately increased in obese individuals. U-shaped relationships were also found between WC and total mortality. About 40% of the excess mortality in the lower BMI range in men was explained by mortality from respiratory diseases. CONCLUSIONS: BMI below 25 in elderly men and women was associated with increased mortality. A modest increase in mortality was found with increasing BMI among obese men and women. Overweight individuals (BMI 25-29.9) had the lowest mortality.

Abstract: Lung cancer causes >1.6 million deaths annually, with early diagnosis being paramount to effective treatment. Here we present a validated risk assessment model for lung cancer screening. The prospective HUNT2 population study in Norway examined 65,237 people aged >20years in 1995-97. After a median of 15.2years, 583 lung cancer cases had been diagnosed; 552 (94.7%) ever-smokers and 31 (5.3%) never-smokers. We performed multivariable analyses of 36 candidate risk predictors, using multiple imputation of missing data and backwards feature selection with Cox regression. The resulting model was validated in an independent Norwegian prospective dataset of 45,341 ever-smokers, in which 675 lung cancers had been diagnosed after a median follow-up of 11.6years. Our final HUNT Lung Cancer Model included age, pack-years, smoking intensity, years since smoking cessation, body mass index, daily cough, and hours of daily indoors exposure to smoke. External validation showed a 0.879 concordance index (95% CI [0.866-0.891]) with an area under the curve of 0.87 (95% CI [0.85-0.89]) within 6years. Only 22% of ever-smokers would need screening to identify 81.85% of all lung cancers within 6years. Our model of seven variables is simple, accurate, and useful for screening selection.

Abstract: BACKGROUND: The objective of this study was to examine the association of maternal and paternal height with pregnancy length, and with the risk of pre- and post-term birth. In addition we aimed to study whether cardiovascular risk factors could explain possible associations. METHODS: Parents who participated in the Nord-Trondelag Health Study (HUNT 2; 1995-1997) were linked to offspring data from the Medical Birth Registry of Norway (1997-2005). The main analyses included 3497 women who had delivered 5010 children, and 2005 men who had fathered 2798 pregnancies. All births took place after parental participation in HUNT 2. Linear regression was used to estimate crude and adjusted differences in pregnancy length according to parental heights. Logistic regression was used to estimate crude and adjusted associations of parental heights with the risk of pre- and post-term births. RESULTS: We found a gradual increase in pregnancy length by increasing maternal height, and the association was essentially unchanged after adjustment for maternal cardiovascular risk factors, parental age, offspring sex, parity, and socioeconomic measures. When estimated date of delivery was based on ultrasound, the difference between mothers in the lower height quintile (<163 cm cm) and mothers in the upper height quintile (>/= 173 cm) was 4.3 days, and when estimated date of delivery was based on last menstrual period (LMP), the difference was 2.8 days. Shorter women (< 163 cm) had lower risk of post-term births, and when estimated date of delivery was based on ultrasound they also had higher risk of pre-term births. Paternal height was not associated with pregnancy length, or with the risks of pre- and post-term births. CONCLUSIONS: Women with shorter stature had shorter pregnancy length and lower risk of post-term births than taller women, and when EDD was based on ultrasound, they also had higher risk of preterm births. The effect of maternal height was generally stronger when pregnancy length was based on second trimester ultrasound compared to last menstrual period. The association of maternal height with pregnancy length could not be explained by cardiovascular risk factors. Paternal height was neither associated with pregnancy length nor with the risk of pre- and post-term birth.

Abstract: OBJECTIVE: To assess the predictive value of estimated cardiorespiratory fitness (eCRF) and evaluate the additional contribution of traditional risk factors in cardiovascular disease (CVD) mortality prediction. PARTICIPANTS AND METHODS: The study included healthy men (n=18,721) and women (n=19,759) aged 30 to 74 years. A nonexercise algorithm estimated cardiorespiratory fitness. Cox proportional hazards models evaluated the primary (CVD mortality) and secondary (all-cause, ischemic heart disease, and stroke mortality) end points. The added predictive value of traditional CVD risk factors was evaluated using the Harrell C statistic and net reclassification improvement. RESULTS: After a median follow-up of 16.3 years (range, 0.04-17.4 years), there were 3863 deaths, including 1133 deaths from CVD (734 men and 399 women). Low eCRF was a strong predictor of CVD and all-cause mortality after adjusting for established risk factors. The C statistics for eCRF and CVD mortality were 0.848 (95% CI, 0.836-0.861) and 0.878 (95% CI, 0.862-0.894) for men and women, respectively, increasing to 0.851 (95% CI, 0.839-0.863) and 0.881 (95% CI, 0.865-0.897), respectively, when adding clinical variables. By adding clinical variables to eCRF, the net reclassification improvement of CVD mortality was 0.014 (95% CI, -0.023 to 0.051) and 0.052 (95% CI, -0.023 to 0.127) in men and women, respectively. CONCLUSION: Low eCRF is independently associated with CVD and all-cause mortality. The inclusion of traditional clinical CVD risk factors added little to risk discrimination and did not improve the classification of risk beyond this simple eCRF measurement, which may be proposed as a practical and cost-effective first-line approach in primary prevention settings.

Abstract: BACKGROUND: Dementia is an increasing public health challenge, and the number of individuals affected is growing rapidly. Mental disorders and symptoms of mental distress have been reported to be risk factors for dementia. The aim of this study was to examine whether midlife mental distress is a predictor for onset of dementia later in life. METHODS: Using data from a large population-based study (The Nord-Trondelag Health Study; HUNT1) linked to a dementia registry (The Health and Memory study; HMS) enabling a maximum 27 years of follow-up, we ascertained mental distress and subsequent dementia status for 30,902 individuals aged 30-60 years at baseline. In HUNT1, self-reported mental distress was assessed using the four-item Anxiety and Depression Index (ADI-4). Dementia status was ascertained from HMS, which included patient and caregiver history, cognitive testing and clinical and physical examinations from the hospitals and nursing homes serving the catchment area of HUNT1. In the main analysis, unadjusted and adjusted logistic regression models were computed for the prospective association between mental distress and dementia. In secondary analyses, two-way age and gender interactions with mental distress on later dementia were examined. RESULTS: A 50% increased odds for dementia among HUNT1-participants reporting mental distress was found (crude odds ratio (OR): 1.52; 95% CI 1.15-2.01), and a 35% increase in the fully adjusted model (OR 1.35; 95% CI 1.01-1.80). In secondary analyses, we found evidence for a two-way interaction with age on the association between mental distress and dementia (p = 0.030): the age- and gender adjusted OR was 2.44 (95% CI 1.18-5.05) in those aged 30-44 years at baseline, and 1.24 (0.91-1.69) in 45-60 year olds. CONCLUSIONS: Our results indicate an association between midlife mental distress and increased risk of later dementia, an association that was stronger for distress measured in early compared to later midlife. Mental distress should be investigated further as a potentially modifiable risk factor for dementia.

Abstract: Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 x 10(-4) ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 x 10(-9) ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.

Abstract: BACKGROUND: Poor health is clustered in families, and partners might influence each other. We studied possible consequences of living with a spouse with poor health or unhealthy lifestyle on mortality and work disability. METHODS: In total, 18 943 couples from the HUNT2 Study (1995-97) were linked to national registries and followed until December 2007, identifying deaths and disability pension retirements. Couple's mean exposures were included together with the individual's deviation from the couple mean in discrete time multilevel logistic regression. RESULTS: There was weak evidence of associations between partner's health and risk of dying. Associations between couples slightly exceeded associations within couples for smoking [odds ratio (OR) within 1.57 (95% confidence interval (CI): 1.38-1.78); OR between 1.88 (95% CI: 1.70-2.08), P value for difference 0.027] and education [OR within 1.07 (95% CI: 0.99-1.15); OR between 1.17 (1.11-1.23), P value for difference 0.065]. Indicators of partner's health, such as self-rated health [OR within 3.17 (95% CI: 2.80-3.58); OR between 3.92 (95% CI: 3.50-4.40), P value for difference 0.014], insomnia [OR within 1.39 (95% CI: 1.18-1.64); OR between 2.11 (95% CI: 1.86-2.53), P value for difference