Är det farligt att snusa vad vet vi idag? Mats Wallström Avd för käkkirurgi

3000 kemiska produkter Tobak 40-45% Vatten 45-60% Na-karbonate-Högt pH 1.5-3.5% Salt 1.5-3.5% Fuktämnen 1.5-3.5% Smakämnen < 1% Nikotin

Nikotin-alkaloid Autonoma CNS-belöning Ganglier Vasomotorisk- Center Adremalin Parasymp Vasomotorisk- Center Puls,O2, Arrth, Vasocon Binjurebarken Adrenalin Ökad metabol effekt Baroreceptorer Skelett- Muskelaturen. Stim Blockad Bolinder-1997

Tobaksspecifika nitrosaminer 23 st i snus TSNA Tobacco-specific N-nitrosamine NNN N-nitrosonornicotine NNK 4 (metylnitrosamino)-1-(3pyridyl)- 1-butanone Cancerframkallande

pH är den avgörande faktor hur mycket nikotin sommabsorberas genom slemhinnan och med vilken hastighet Tomar SL. Tob Control 1997 6(3):219-25.

Snuskonsumption män % kvinnor % Sverige: 19 4 Norge: 11 2 USA 15? 2

Snuff-induced lesions - A Clinical and Experimental Study - Hirsch1983 Djurexperiment Rat incisors Lip canal filled with snuff 10 h per day Surgically created canal in the lip Snuff-induced lesions - A Clinical and Experimental Study - Hirsch1983

Djurexperiment Johansson Sl et al. Snuff-induced carcinogenisis: Effect of snuff initiated with 4-nitrouinoline N-Oxide Cancer research-1989 Larsson PA et al. Snuff tumorigenisis: effects of long- term snuff administrat after initiation with 4NQO and Herpes simplex virus type 1. J Oral Pathol Med -1989 Park NH et al. Role of Virus in Oral Cancinogenesis- NIH publication-1993 Grasso. Smokeless Tobacco and Oral Cancer: An Assessment of Evidence Derived from Laboratory Animals. Food and Chem Toxicol - 1998

Effekter på kroppen Lokala effekter Slemhinnan Parodontala Karies Allmänna Vanebildande Hjärta-kärl Graviditet Spädbarnsdöd Diabetes Cancer

Snus läsioner 1963 – Pindborg undersökte 12 kroniska snusare. Inga dysplasier. 1976 – Axéll delade in snusläsionen i 4 olika kliniska grader. 1982 – Hirsch redogjorde för 50 kroniska snusare. Lätt dysplasi i alla kliniska grader 1991 – Andersson biopserade 250 snusare. Några dysplasier i materialet 2011 – Wallström undersökte reversibiliteten efter 6 månaders snusstopp att läsionen inte läkte ut.

Tandlossning Gingivala retraktioner: 1965 - van Wyk noterad att angränsande tänder hade gingival retraktioner. 1980 - Modeér en ökad gingivit trots plackkontroll 1989 – Andersson fann att 23% vs 3% hade gingiva retraktioner beroende på förpacknings form

Tandlossning 2004, 2006, 2006. 3 svenska studier fann ingen signifikant ökad bennedbrytning hos snusare jmf med icke tobaksnyttjare 2005. Bland 12 000 snusare I en amerikansk studie var det dubbelt så vanligt med avancerad tandlossning

Karies USA Skandinavien 4 studier hos unga individer. En studie visade på positiv korrelation mellan snusning-karies och gingivit. Skandinavien Hirsch-91 Snusare hade ett significant högre DMFT

Cancer

Cancer The working group stated that “there is sufficient evidence in humans to establish smokeless tobacco as carcinogenic, i.e. smokeless tobacco causes cancer of the oral cavity and pancreas.”

Clinical data of the 15 patients with snuff induced oral cancer   Case Age Location Snuff use (years) Smoking G.S. 75 Upper jaw 61 No N.L. 91 Upper jaw 70 Not for 70 years F.A. 72 Upper jaw 42 No K-G.B. 75 Upper jaw 71 No S.W. 50 Upper jaw 8 Prior to snuff use D.D. 85 Upper jaw 20 No B.W. 79 Lower jaw 45 Not for 30 years F.N. 89 Upper jaw 69 No S.E. 52 Upper jaw 20 Concomitant to snuff S.L. 67 Upper jaw 18 Not for 18 years H.G. 78 Lower jaw - No S-Å.G. 81 Upper jaw 66 No X.X. 74 Upper jaw 40 No R.F. 84 Upper jaw 30 No X.X. 67 Upper jaw 49 Not for 48 years ORAL CANCER IN SWEDISH SNUFF-DIPPERS Hirsch et al Submitted

Cancer Years Range Mean age at time of diagnosis: 74,6 50-91 Median age at time of diagnosis: 75   Mean duration with the snuff habit: 43,5 8-71 Median duration with the snuff habit: 47   Mean age at start of snuff use: 30,8 4-65 Median age at start of snuff use: 31

Cancer 3 svenska studier Schildt EB: Int J Cancer. 1998: Oral snuff, smoking habits and alcohol consumption in relation to oral cancer in a Swedish case-control study. 410p/410c OR 0.7 CI 95% 0.4-1.1 Rosenqvist K: Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology of oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. 135p/320c OR 1.1 CI 95% 0.5-25 Lewin F: Cancer. 1998: Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. 605p/756c RR 4.7 for ever users CI 95% 1.6-13.8

Cancer 2 svenska studier Roosaar A et al. 2008 Int J Cancer Cancer and mortality among users and nonusers of snus. Cohort 9976p 1973-2002. Ökad cancerrisk oral och orofaryngeal RR 3.1 CI 95% 1.5-6.6 Ökad dödlighet: HR 1.10 CI 95% 1.01-1.21 Luo J et al. 2007 Lancet: Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study. 279897p Pancreascancer RR 2.0 CI 95% 1.2-3.3 1 norsk studie Boffetta P. 2005- In J Cancer . Smokeless tobacco use and risk of cancer of the pancreas and other organs. Cohort 10136p Pancreas cancer: RR 1.67 CI 95% 1.12-2.5

Long-term use of smokeless of smokeless tobacco Målsättning: Öka kunskapen om snusningens hälsoeffekter, Främst avseende risken för hjärt- och kärlsjukdom Bolinder G, Avhandling -97

Long-term use of smokeless of smokeless tobacco Material och metod: 1971-78 hälsoundersöktes totalt 135 036 byggnadsarbetare av bygghälsan. 32 546 hade aldrig nyttjat tobak 14 983 rökte > 15cig/dag 6 297 var enbart snusare Bolinder G, Avhandling -97

Long-term use of smokeless of smokeless tobacco Symptom, sjukfrånvaro och förtidspensionering hos snusare jämfört med rökare och tobaksfria I byggbranschen. Ökad risk för död I hjärt-och kärl sjukdom hos snusare. Fysisk arbetsförmåga vid långvarigt snusbruk. Metabola riskfaktorer för hjärt-kärlsjukdom vid snusning. Snusning och åderförkalkning-ultraljudsundersökning av intima-media-tjocklek I arteria carotis. 24-timmars blodtrycksmätning hos snusare, rökare och icke-tobaksbrukare. Bolinder G, Avhandling -97

Long-term use of smokeless of smokeless tobacco En av slutsatserna: 50% av alla dödsfall beror på hjärtkärl –sjukdommar. Vid en måttlig riskökning med en relativ risk på 1.4 och då 20% av svenska män snusar betyder det att ca 1300 dödsfall om året kan tillskrivas snusningen. Bolinder G, Avhandling -97

Hjärt-kärlsjukdomar Fall-kontroll studier Scandinavien Cohort studie OR CI Bolinder-94 34-54år Angina-typ 2.0 1.49-2.9 Stroke 1.9 0.6-5.7 H-K död 2.1 1.5-2.9 55-64år Angina 1.2 1.0-1.5 Stroke 1.2 0.7-1.8 H-K död 1.0 1.0-1.4 Fall-kontroll studier MONICA 2 studier som inte visade på någon ökad risk för snusare att få hjärtinfarkt jmf med icke-snusare

Hjärt-kärlsjukdomar Kliniska epidemiologiska studier fokuserar på hjärt-kärlsjukdommar, Hjärtinfarkt, aterioskleros, stroke, högt blodtryck och metabola syndrom. Boffetta P, Straif K 2009 Lancet. Use of smokeless tobacco and risk of myocardial infarction and stroke: systematic review with meta-analysis. Dödlig hjärtinfarkt RR 1.13 95% CI 1.06-1.21 Dödlig stroke 1.40 1.28-1.54 Hergens 2007 J I Medicin Long-term use of Swedish moist snuff and the risk of myocardial infarction amongst men. Dödlig myocard RR 1.96 95% CI 1.08-3.58 Henley 2005 Cancer Causes Contro. lTwo large prospective studies of mortality among men who use snuff or chewing tobacco. Ökad dödlighet HR 1.17 1.11-1.23, HR 1.18 1.08-1.29

Metabolt syndrom/ diabetes Norberg, 2006, Scand J Public Health. Contribution of Swedish moist snuff to the metabolic syndrome: a wolf in sheep's clothing? Longitudinell cohort 16492p efter 10 år. Metsy bland snusare OR 1.6 (1.26-2.15) höga triglycerider OR 1.6 (1.30-1.95), obesitas 1.7 (1.36-2.18) Persson, 2000 J Intern Med.. Cigarette smoking, oral moist snuff use and glucose intolerance. J Intern Med. 2000 Cross sectional study 3128 män där 52% hade en ärftlig belastning Mer än 3 dosor/vecka OR 2.7 (1.3-5.5) Eliasson M, Rodu B. 2004 J Intern Med. Influence of smoking and snus on the prevalence and incidence of type 2 diabetes amongst men: the northern Sweden MONICA study. Snusare OR 1.34 (0.65-2.)7 and Har snusat OR 1.18 (0.48-2.9)

Effect of Swedish snuff on preterm birth OBJECTIVE: To compare the effects of Swedish snuff and cigarette smoking on risks of preterm birth. DESIGN: Population-based cohort study. All live, singleton births in Sweden 1999-2006. MAIN OUTCOME MEASURES: Very (<32 weeks) and moderately (32-36 weeks) preterm birth. Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.

Effect of Swedish snuff on preterm birth METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate relative risks for preterm birth in snuff users (n = 7607), light smokers (1-9 cigarettes/day; n = 41 436) heavy smokers (ten or more cigarettes/day; n = 16 951) non-tobacco users (n = 503 957) as reference. Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.

Effect of Swedish snuff on preterm birth RESULTS: Compared with non-tobacco users, snuff users had increased risks of both very (adjusted OR 1.38; 95% CI 1.04-1.83) and moderately (adjusted OR 1.25; 95% CI 1.12-1.40) preterm birth. Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.

Effect of Swedish snuff on preterm birth CONCLUSIONS: The use of Swedish snuff was associated with increased risks of very and moderately preterm birth with both spontaneous and induced onsets. Swedish snuff is not a safe alternative to cigarette smoking during pregnancy. Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.

Maternal use of Swedish snuff (snus) and risk of stillbirth. BACKGROUND: Swedish snuff has been discussed internationally as a safer alternative to tobacco smoking. International cigarette manufacturers are promoting new snuff products, and the use of Swedish snuff is increasing, especially among women of childbearing age. The effect of Swedish snuff on pregnancy complications is unknown.

Maternal use of Swedish snuff and risk of stillbirth. METHODS: In this population-based cohort study, we estimated the risk of stillbirth in snuff users (n = 7629), light smokers (1-9 cigarettes/day; n = 41,488), and heavy smokers (≥10 cigarettes/day; n = 17,014), using nontobacco users (n = 504,531) as reference.

Maternal use of Swedish snuff and risk of stillbirth. RESULTS: Compared with nontobacco users, snuff users had an increased risk of stillbirth (adjusted OR= 1.6 [95% CI= 1.1-2.3]); the risk was higher for preterm (<37 weeks) stillbirth (2.1 [1.3-3.4]). For light smokers, the adjusted odds ratio of stillbirth was 1.4 (1.2-1.7) and the corresponding risk for heavy smokers was 2.4 (2.0-3.0). Wikstrom AK Epidermiology 2010 Nov;21(6):772-8.

Maternal use of Swedish snuff and risk of stillbirth. CONCLUSIONS: Use of Swedish snuff during pregnancy was associated with a higher risk of stillbirth. The mechanism behind this increased risk seems to differ from the underlying mechanism in smokers. Swedish snuff does not appear to be a safe alternative to cigarette smoking during pregnancy. Wikstrom AK Epidermiology 2010 Nov;21(6):772-8.

Harm reduction Definition: A product is harm reducing if it lowers total tobacco – related mortality and morbidity Even though use of that product may involve Continued exposure to tobacco toxicants Clearing the Smoke., Assessing the Scienece Base for Tobacco Harm Reduction

Interventionsstudier Farmakologiska studier: CI 95% Buprion - 1 studie OR 1.0 0.23-4.37 NRT - 2 studie (tuggimmi) OR 0.98 0.59-1.63 NRT – 3 studier (plåster) OR 1.16 0.88-1.54 Betendevetenskapliga studier: Ind/grupp – 8 studier OR 2.42 1.79-3.24 Cochrane 2007