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Rauchen und Lungenkrebs

Wie falsch lag Fisher wirklich?

Smoking and lung cancer

How wrong was Fisher really?

Zusammenfassung

Sir Ronald Aylmer Fisher, der wohl berühmteste und produktivste Statistiker des 20. Jahrhunderts, hat zeit seines Lebens den kausalen Zusammenhang zwischen dem Tabakrauchen und der Entstehung von Lungenkrebs angezweifelt. Er zog stattdessen einen genetischen „Confounder“ als Erklärung für die zwischen beiden Faktoren bestehende statistische Assoziation in Betracht, d. h. er konstatierte ein Gen, das sowohl das Rauchverhalten als auch die Krebsätiologie beeinflusst. Es gab viele Versuche, Fishers Starrsinn in dieser Angelegenheit zu erklären. Neben außerwissenschaftlichen Gründen (Fisher war selbst leidenschaftlicher Raucher) spielte wohl auch Fishers Sorge um den Stellenwert valider statistischer Methoden in der medizinischen Forschung eine entscheidende Rolle. Genomweite Assoziationsanalysen (GWAS) zum Rauchverhalten und zum Lungenkrebs haben in jüngster Vergangenheit Hinweise dafür geliefert, dass Fishers Überlegungen vielleicht doch ein Fünkchen Wahrheit enthielten und dass sich sein Confounder in Form des Gens für die Nikotinrezeptor-Untereinheit α5 auf Chromosom 15q25 wiederfinden könnte.

Abstract

Sir Ronald Aylmer Fisher was the most famous and most productive statistician of the 20th century. Throughout his life, however, Fisher doubted the causal relationship between tobacco smoking and lung cancer. Instead, he invoked a genetic confounder to explain the statistical association between the two factors, i.e., he believed in the existence of a gene that plays a role in both cancer etiology and smoking behavior. There have been many attempts to explain Fisher’s stubbornness regarding this matter. In addition to nonscientific reasons (Fisher was himself a keen smoker) worries about the future importance of valid statistical methodology in medical research also may have played an important role. Interestingly, recent genome-wide association studies (GWAS) of smoking behavior as well as lung cancer have revealed that there may have been a grain of truth in Fisher’s idea and that his confounder may coincide with the gene encoding nicotine receptor subunit α5 on chromosome 15q25.

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Correspondence to M. Krawczak.

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(Ausarbeitung eines Vortrags anlässlich des Abschiedssymposiums für Prof. Dr. Thomas Wienker, Bonn, 17. Februar 2011)

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Krawczak, M. Rauchen und Lungenkrebs. medgen 23, 400–406 (2011). https://doi.org/10.1007/s11825-011-0291-y

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Schlüsselwörter

  • Lungenkrebs
  • Tabakrauchen
  • Confounder
  • Nikotinrezeptor
  • Kausalität

Keywords

  • Lung cancer
  • Tobacco smoking
  • Confounder
  • Nicotine receptor
  • Causality