Recent health impact research in Denmark Mette Sørensen Senior researcher Diet, Genes and Environment Danish Cancer Society Research Center Denmark Present some of the results from the more recent studies we have conducted in my research group at the….

? Traffic noise and health Hypertension Ischemic heart disease Stroke Obesity Diabetes Atrial fibrillation Heart failure Cancer ? As most of you know there has been a number of studies on…

Traffic noise and health Obesity Diabetes Atrial fibrillation Heart failure Cancer Potential biological mechanisms Epidemiological studies (noise/sleep/stress) Design of our study Results of our study As most of you know there has been a number of studies on…

Mechanisms, obesity/diabetes Traffic noise Stress response: autonomic nervous system and HPA axis Disturbance of sleep (duration, quality) Cortisol Metabolic disease – focus on obesity and diabetes ↓ Insulin levels ↓ Insulin sensitivity ↓ Glycose tolerance ↑ Morning glucose ↓ Leptin (satiety) ↑ Ghrelin (hunger) Obesity, diabetes

Obesity and diabetes Epidemiological studies on sleep disturbance: Short sleep duration -> obesity in children Reduced sleep quality and duration -> waist circumference and BMI in adults Reduced sleep quality and quantity -> increase risk of diabetes Meta-analysis: 10 prospective studies, > 100,000 participants, 3,500 diabetes cases Traffic noise and obesity Two Swedish studies -> an association between traffic noise and obesity (Pyko et al; Eriksson et al) One study suggest no association (Oftedal et al)

Study population Diet, Cancer and Health cohort Enrolment in 1993-1997 57,053 persons aged 50-64 years Copenhagen and Aarhus Questionnaire Lifestyle: e.g. diet, smoking, alcohol SES: e.g. education Weight, height and waist circumference measured

National registries Long tradition for registers in Denmark Personal identification number (PIN) -> all Danes at birth Reporting to registers by law -> almost complete Generally high validity of registers Central Population Registry (1971) all present and historical addresses from 1987-2011 The National Patient Registry (1977) - all hospital submissions The National Diabetes Registry (1995) The Cancer Registry (1942)

Noise exposure, road and rail SoundPLAN – the Nordic Prediction Method Geocode and height (floor) for each address (1987-2011) Building polygons All road lines with > 1000 vehicles Traffic composition (heavy/light) Yearly average daily traffic Traffic speed All railway links Annual average daily train lengths Train types and travel speed Noise barriers AirGIS – dispersion model for estimation of air pollution

Obesity, results Design Results for road traffic noise BMI, waist circumference, fat percentage of 57,000 persons (50-64 y) Long-term residential road traffic noise Adjusted for age, sex, and socioeconomic factors Results for road traffic noise ↑ BMI ↑ waist circumference ↑ fat percentage Christensen et al, 2015

Traffic noise and diabetes Sørensen et al, 2013, Denmark Cohort study: 57,053 participants 3,869 diabetes cases from national register RESULTS 10 dB rise in 5-years mean road traffic noise 11 % increase in risk (IRR: 1.11 (1.05-1.18))

Atrial fibrillation and heart failure Abnormal heart rhythm -> rapid and irregular beating Increased cardiovascular morbidity and mortality 10 % at age 80 years Prevalence rising Heart failure Complex syndrome -> end-stage of other CVD Weakened heart muscle -> not enough blood to meet body's needs Most frequent reason for hospitalization among older people

Mechanisms, AF and heart failure Traffic noise Stress response: autonomic nervous system and HPA axis Disturbance of sleep Impaired immune system Cortisol Hypertension, IHD Endothelial dysfunction ↑ glycogen concentration within atrial myocytes Changes of atrial electrophysiology Systemic inflammation Atrial fibrillation, heart failure

Traffic noise and atrial fibrillation Monrad et al, 2016, Denmark Cohort study: 57,053 participants Long-term road traffic noise (5-years mean) 2,692 persons developed A-fib (national register) RESULTS 10 dB rise in 5-years mean road traffic noise 6 % increase in risk (IRR: 1.06 (1.00-1.12)) adjustment for air pollution reduced estimate (difficult to separate association from exposure to air pollution)

Traffic noise and heart failure Sørensen et al, submitted Cohort study: 57,053 participants Long-term road traffic noise (10-years mean) 2,550 persons developed heart failure (national register) RESULTS 10 dB rise in 10-years mean road traffic noise 14 % increase in risk (IRR: 1.14 (1.08-1.21)) before air pollution 8 % increase in risk (IRR: 1.08 (1.00-1.16)) after air pollution MI, diabetes, hypertension, chronic obstructive pulmonary disease

Cancer Breast cancer Prostate cancer Non-Hodgkin’s lymphoma originating from lymphoid tissue

Impaired immune response / inflammation Mechanisms, cancer Traffic noise Stress response: autonomic nervous system and HPA axis Disturbance of sleep (duration, quality) ↑ Cortisol Circadian rhythm disruption ↓ Apoptosis ↑ Angiogenesis ↓ Melatonin Impaired immune response / inflammation ↓ DNA repair ↑ Estrogen ↓ Antioxidant Oxidative stress Cancer

Breast cancer Sørensen et al, 2014 Cohort study: 30,000 women Long-term road traffic AND railway noise (5-years mean) 1,219 women developed breast cancer (national register) Estrogen receptor: 858 positive/203 negative cases Adjustment: Parity, age first birth, HRT, lifestyle, SES

Breast and prostate cancer Breast cancer: Sørensen, 2014 Road and railway: no association with ER positive BC Among ER negative BC: Road: IRR = 1.23 (1.00-1.51) Railway: IRR = 1.38 (1.01-1.89) Prostate cancer: Roswall, 2015 1,457 cases from national register No associations with road traffic or railway noise

Non-Hodgkin’s lymphoma Well-established risk factor -> suppression of immune system Sørensen et al, 2015 Case-control study (all Denmark): 2,753 cases / 4,743 controls Long-term residential road traffic noise Adjusted for sex, age and SES Traffic noise   Cases Adjusted OR (95% CI) Road traffic noise, 5-y < 55 dB 1,103 1.00 55-65 dB 1,256 0.98 (0.88-1.08) ≥ 65 dB 394 1.18 (1.01-1.37)

Conclusions Diabetes and obesity “Novel” major cardiovascular diseases road traffic noise associated with diabetes we and others find traffic noise to be associated with obesity “Novel” major cardiovascular diseases association between road traffic noise and atrial fibrillation association between road traffic noise and heart failure

Conclusions Cancer road traffic and railway noise associated with estrogen receptor negative breast cancer road traffic noise not associated with prostate cancer road traffic noise above 65 dB associated NHL MORE STUDIES ARE NEEDED OVERALL CONCLUSION Research suggests that traffic noise is associated with other major diseases than IHD, stroke and hypertension

Thank you for your attention E-mail: mettes@cancer.dk