|
|
Markaki, M., Tsamardinos, I., Langhammer, A., Lagani, V., Hveem, K., & Roe, O. D. (2018). A Validated Clinical Risk Prediction Model for Lung Cancer in Smokers of All Ages and Exposure Types: A HUNT Study. EBioMedicine, 31, 36–46.
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.
|
|
|
|
Sorli, K., Thorvaldsen, S. M., & Hatlen, P. (2018). Use of Inhaled Corticosteroids and the Risk of Lung Cancer, the HUNT Study. Lung, 196(2), 179–184.
Abstract: BACKGROUND: Inflammation plays a central role in chronic obstructive pulmonary disease and lung cancer carcinogenesis. Inhaled corticosteroids (ICS) reduce inflammation. This study has investigated whether ICS use is associated with a lower risk of lung cancer. MATERIALS AND METHODS: Data from the Nord-Trondelag Health Study (HUNT2 Survey, 1995-1997) were merged with The Cancer Registry of Norway and Norwegian Cause of Death Registry. From a total of 65,215 participants, those with chronic airway inflammation, defined by FEV1% < 70 and/or chronic cough and expectorate phlegm, were included (N = 4136). Of these, 3041 individuals reported regarding ICS use and were observed for a period of 12 years. Cox regression models were used to calculate the risk of lung cancer with a 95% confidence interval (CI) with sex, age, smoking pack years and FEV1% < 70 as known confounders. RESULTS: Among ICS users (N = 1095). we found a higher, but not significant, incidence of lung cancer N = 39 (3.6%), compared to non-users (N = 1946) with N = 65 (3.3%) cases. Age and smoking were associated with a higher risk, while sex and lung function were not. After adjusting for confounders, ICS use did not change the risk of lung cancer, hazard ratio (HR) 0.968, (95% CI, 0.608-1.540), and p value 0.890. CONCLUSION: ICS use is not associated with a reduced risk of lung cancer in our study population.
|
|
|
|
Sorli, K., Thorvaldsen, S. M., & Hatlen, P. (2018). Use of Inhaled Corticosteroids and the Risk of Lung Cancer, the HUNT Study. Lung, 196(2), 179–184.
Abstract: BACKGROUND: Inflammation plays a central role in chronic obstructive pulmonary disease and lung cancer carcinogenesis. Inhaled corticosteroids (ICS) reduce inflammation. This study has investigated whether ICS use is associated with a lower risk of lung cancer. MATERIALS AND METHODS: Data from the Nord-Trondelag Health Study (HUNT2 Survey, 1995-1997) were merged with The Cancer Registry of Norway and Norwegian Cause of Death Registry. From a total of 65,215 participants, those with chronic airway inflammation, defined by FEV1% < 70 and/or chronic cough and expectorate phlegm, were included (N = 4136). Of these, 3041 individuals reported regarding ICS use and were observed for a period of 12 years. Cox regression models were used to calculate the risk of lung cancer with a 95% confidence interval (CI) with sex, age, smoking pack years and FEV1% < 70 as known confounders. RESULTS: Among ICS users (N = 1095). we found a higher, but not significant, incidence of lung cancer N = 39 (3.6%), compared to non-users (N = 1946) with N = 65 (3.3%) cases. Age and smoking were associated with a higher risk, while sex and lung function were not. After adjusting for confounders, ICS use did not change the risk of lung cancer, hazard ratio (HR) 0.968, (95% CI, 0.608-1.540), and p value 0.890. CONCLUSION: ICS use is not associated with a reduced risk of lung cancer in our study population.
|
|
|
|
Sun, Y. - Q., Langhammer, A., Wu, C., Skorpen, F., Chen, Y., Nilsen, T. I. L., et al. (2017). Associations of serum 25-hydroxyvitamin D level with incidence of lung cancer and histologic types in Norwegian adults: a case-cohort analysis of the HUNT study. Eur J Epidemiol, .
Abstract: Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trondelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Compared with the fourth season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the second and third quartiles (median 39.9 and 51.5 nmol/L) compared with the fourth quartile, with HRs of 0.63 (95% CI 0.41-0.98) and 0.58 (0.38-0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for second and third quartiles: 0.40 (0.22-0.72) and 0.50 (0.27-0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52-1.75) and 0.60 (0.32-1.10)]. Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution.
|
|
|
|
Sun, Y. - Q., Langhammer, A., Wu, C., Skorpen, F., Chen, Y., Nilsen, T. I. L., et al. (2018). Associations of serum 25-hydroxyvitamin D level with incidence of lung cancer and histologic types in Norwegian adults: a case-cohort analysis of the HUNT study. Eur J Epidemiol, 33(1), 67–77.
Abstract: Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trondelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Compared with the fourth season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the second and third quartiles (median 39.9 and 51.5 nmol/L) compared with the fourth quartile, with HRs of 0.63 (95% CI 0.41-0.98) and 0.58 (0.38-0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for second and third quartiles: 0.40 (0.22-0.72) and 0.50 (0.27-0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52-1.75) and 0.60 (0.32-1.10)]. Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution.
|
|
|
|
Theofylaktopoulou, D., Midttun, O., Ueland, P. M., Meyer, K., Fanidi, A., Zheng, W., et al. (2017). Impaired functional vitamin B6 status is associated with increased risk of lung cancer. Int J Cancer, .
Abstract: Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4thvs.1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
|
|
|
|
Theofylaktopoulou, D., Midttun, O., Ueland, P. M., Meyer, K., Fanidi, A., Zheng, W., et al. (2018). Impaired functional vitamin B6 status is associated with increased risk of lung cancer. Int J Cancer, 142(12), 2425–2434.
Abstract: Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4thvs.1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
|
|
