醫學 1950

吸菸與肺癌

理查德·多爾與奧斯汀·布拉德福德·希爾

患肺癌的男性幾乎全是吸菸者——從結局反推，照出了病因。

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In depth · the introduction

肺癌死亡，在一代人的時間裡漲了十五倍——於是兩位研究者問了一個簡單的問題：在死於此病的男性裡，有多少從未吸過菸？答案是：幾乎沒有。

核心想法

你不可能出於倫理去讓人患上癌症，再來檢驗是什麼導致了它。於是多爾與希爾把實驗「倒著」做。他們找來一大批已經患上肺癌的病人（「病例」），又為每一位配上一名沒有患病的相似病人（「對照」）——同性別、同年齡、同醫院。然後，只是簡單地問每個人：你吸不吸菸？

差距大得驚人。在患肺癌的男性中，幾乎每一個都是吸菸者——649 人裡只有 2 人從未吸過菸。而在匹配的健康男性裡，不吸菸的要多得多。把這些數字摞起來，吸菸者落在癌症組裡的可能性，約高出十四倍。這種「病例對比對照」的比較，後來成了醫學中最有力的工具之一。

它是如何誕生的

第二次世界大戰之後，英國的醫生們大為警覺：死於肺癌的人數在一刻不停地攀升。兩個嫌疑領跑——現代城市的煤煙與廢氣，以及變得極為流行的香菸。年輕的醫師理查德·多爾，與剛剛開創了隨機臨床試驗的統計學家奧斯汀·布拉德福德·希爾聯手，要弄清究竟是哪一個。

在 1948 到 1949 這兩年裡，他們派出受過訓練的訪談者，走進二十家倫敦醫院，詢問了一千多名癌症患者，以及同樣多的匹配對照。研究開始時，多爾自己也吸菸；結果如此清晰，以至於他在研究進行到一半時就把菸戒了。他們於 1950 年把論文發表在《英國醫學雜誌》上——恰恰與一支美國團隊報告同一發現的那一週。

它為何重要

那時香菸無處不在——由醫生代言、發給士兵、織進日常生活。要宣稱它正在害死人，需要異常有力的證據，而單憑一項研究是會被駁回的。但這一項，先有一項平行的美國研究印證，又有多爾與希爾自己對四萬名醫生的長期隨訪佐證，慢慢扭轉了大勢。它支撐起其後的警示標籤、廣告禁令與公共衛生宣傳——也教會了醫學：當你無法做實驗時，該如何去追獵疾病的病因。

一個可以想像的畫面

想像某個街區接二連三地起火。你不能為了驗證假設而去放火，於是你改為：走訪每一戶被燒過的房子，再走訪它隔壁同樣普通、卻沒被燒的房子，問問各家廚房裡都有些什麼。如果幾乎每戶失火的人家都有一台故障的取暖器，而沒失火的大多沒有，那麼嫌疑就鎖定了——你壓根不必劃一根火柴。這種「燒過對比沒燒過」的倒推比較，正是病例對照研究所做的：癌症患者對比健康人，問誰吸菸。

它的位置

這是現代流行病學的一塊奠基石。希爾早已給了醫學隨機試驗（它檢驗療法的方式）；在這裡，他與多爾又給了它病例對照研究（它尋找病因的方式）。這項工作，與本館其他幾個醫學轉折點並肩而立；而它的方法——把病人與健康人相比對、權衡其中的機率——如今潛藏在幾乎每一條「什麼對你有益、什麼對你有害」的新聞背後。

The original document

Original source text

Richard Doll & A. Bradford Hill · British Medical Journal 2(4682): 739–748 · September 30, 1950

The increase in lung cancer

The number of deaths attributed to cancer of the lung provides one of the most striking changes in the pattern of mortality recorded by the Registrar-General. For example, in the quarter of a century between 1922 and 1947 the annual number of deaths recorded increased from 612 to 9,287, or roughly fifteenfold. This remarkable increase is, of course, out of all proportion to the increase of population — both in total and, particularly, in its older age groups.

The method of the investigation

Twenty London hospitals were asked to co-operate by notifying all patients admitted to them with carcinoma of the lung, stomach, colon, or rectum. … On receipt of the notification an almoner, engaged wholly on research, visited the hospital to interview the patient, using a set questionary.

As well, however, as interviewing the notified patients with cancer of one of the four specified sites, the almoners were required to make similar inquiries of a group of “non-cancer control” patients. … for each lung-carcinoma patient visited at a hospital the almoners were instructed to interview a patient of the same sex, within the same five-year age group, and in the same hospital at or about the same time.

The result

It will be seen that the vast majority of men have been smokers at some period of their lives, but also that the very small proportion of those with carcinoma of the lung who have been non-smokers (0.3%) is most significantly less than the corresponding proportion in the control group of other patients (4.2%).

[ … ]

This is not necessarily to say that smoking causes carcinoma of the lung. The association would occur if carcinoma of the lung caused people to smoke or if both attributes were end-effects of a common cause. The habit of smoking was, however, invariably formed before the onset of the disease … so that the disease cannot be held to have caused the habit ; nor can we ourselves envisage any common cause likely to lead both to the development of the habit and to the development of the disease 20 to 50 years later.

We therefore conclude that smoking is a factor, and an important factor, in the production of carcinoma of the lung.

Richard Doll · A. Bradford Hill · Statistical Research Unit of the Medical Research Council, London · 1950