Int. J . Cancer: 5, 152-156 (1970)

CANCER OF THE OESOPHAGUS: FURTHER EVIDENCE OF THE RELATION TO DRINKING HABITS IN FRANCE

A. J. TLJYNS Epidemiology Unit, International Agency for Research on Cancer,

16 Avenue Markchal Foch, Lyons, France

Previous studies have shown a correlation between mortality from cancer of the oesophagus and that from ‘’ alcoholism ” and cirrhosis. It is now shown that the correla- tion is greater with the former than with the latter; as ‘‘ alcoholism” deaths occur rather in spirit drinkers, this correlation may indicate that it is for this category of drinkers that the risk of oesophageal cancer is greatest. The pattern of the geographic relation between ‘ I alcoholism ’’ and oesophageal cancer is consistent with the hypothesis that spirit drinking is a necessary but not a sufficient condition for the development of oesophageal cancer.

The association between consumption of alcohol and cancer of the oesophagus has repea- tedly been demonstrated both by retrospective studies of cases and controls (Schwartz et al . , 1962; Wynder and Bross, 1961) and by geo- graphical studies (Lasserre, 1963; Lasserre et al . , 1967; Aubenque et al., 1956).

From Wynder and Bross’s study (1961) there is some indication that the increase in risk for the heavy drinkers is most marked for the heavy whisky drinkers while for beer and wine drinkers, the risk was also greater than for the non- drinkers, but to a lesser extent. Within the scope of further epidemiologic research on cancer of oesophagus now under preparation by the Inter- national Agency for Research on Cancer (IARC), an attempt was made to determine whether this distinction between spirit drinkers and beer or wine drinkers associated with cancer of the oesophagus could be confirmed by a further analysis of geographical data available in France.

In the studies published so far on this subject. a relation was established between oesophageal cancer mortality and mortality from “alcoholism”, the latter being measured by the summation of two components, namely “ acute or chronic

alcoholism ” and “ liver cirrhosis ”, respectively defined by items numbered 307, 322 and 581 in the International Classification of Causes of Death by WHO, 1957. Although this is a tradi- tional and justified method for measuring the loss of human life due to the misuse of alcohol, the two components correspond to two different groups of diseases occurring in drinkers and eventually causing their death.

There is little doubt that fatal cirrhosis in a country like France is mainly associated with drinking and that the bulk of deaths classified under No. 581 can be attributed to alcoholism; cirrhosis caused by something else is a rare event as compared with alcoholic cirrhosis. The disease is frequent in regular wine and beer drinkers. As to alcoholic psychoses and “acute or chronic ethylism ”, psychiatrists, neurologists and clini- cians say that most often these diseases appear in heavy spirit drinkers. It is believed that the psychogenic or neurologic effects are due as much to alkaloids or other substances dissolved in the drinks as to the ethylic alcohol itself. It is generally agreed that, depending upon what he drinks and how much, the drinker will either develop a cirrhosis if he drinks regularly beer or wine, or a

Received: August IS , 1969.

152

CANCER OF THE OESOPHAGUS

neuro-psychiatric syndrome if he rather turns to distilled alcohol such as whisky or any of the large variety of spirits and liqueurs available in France.

Insofar as mortality from “ alcoholism ” (Nos. 307 and 322) and from liver cirrhosis (No. 581) may thus refer to two categories of drinkers differing as to the kind of alcohol they use, it was considered worth while to study each one independently as to its relation to cancer of the oesophagus.

MATERIAL AND METHODS

Mortality data by age and sex for alcoholism (Nos. 307 and 322) and for liver cirrhosis (No. 581) are published each year for each dipartement by the “ Institut National de la Statistique et des Etudes Economiques ” (INSEE). Similar data are not routinely available for oesophageal cancer but they were kindly given to me by Dr. Lasserre, who had used them for previous work (1963). The data for the four years 1960 to 1963 have been analyzed.

The analysis has been limited to males aged 45-64 in order to eliminate the disturbing effect of ill-defined causes in older age groups, as was done previously by Lasserre et al. (1967). Age- specific yearly mortality rates were computed separately for cancer of the oesophagus, for ‘‘ alcoholism ” and for liver cirrhosis as well as for the two latter together. Maps were drawn and correlations calculated for each pair of data sets at the level of the dipartement and at the level of the province.

RESULTS

The overall correlation at the level of the dipartements between cancer of the oesophagus and alcoholism and cirrhosis is r = 0.54. This is lower than the figure obtained by Lasserre et al. (1967) when they did a similar analysis for the years 1954 to 1959; yet it is significant at the level of p G001. The correlation with cirrhosis only, however, is definitely lower: r = 0.37, while on the contrary, the correlation with “ alcoholism ” is much higher; r = 0.64.

Regrouping the dipartements into 21 regions (a pattern which became almost official last year) the corresponding values are slightly higher but remain placed in the same order. All these results are summarized in Table I and illustrated by maps (Fig. 1 , 2 and 3).

The scatter diagram (Fig. 4) is another illustra- tion of the relation between mortality from “ alcoholism ” and mortality from cancer of the oesophagus. All the French dipartements where the rate for the latter is 50 per 100,000 or more, have a mortality rate for alcoholism that is never inferior to 70 per 100,000. All these dipartements are located in the west of France. The reciprocal, however, is not true; there are a few dipartements having a high rate for alcoholism together with a fairly normal rate (30 to 40 per 100,000) for cancer of the oesophagus. The three main exam- ples of such a situation are Haute Savoie (74) l, Savoie (73) and Ardennes (08) l .

Numbers refer to code numbers of the diparte- ments.

TABLE I

CORRELATION BETWEEN MORTALITY RATES FROM OESOPHAGEAL CANCER A N D MORTALITY RATES FROM I‘ ALCOHOLISM ’* AND LIVER CIRRHOSIS.

MALES AGED 45-64. YEARS 1960-1963

At the level ICD (WHO) Type of correlation of the 88 of the 21

ddpartemenrs regions

At the level

150 and 307-322+581 Cancer of oesophagus and “ alcoholism ” plus cirrhosis 0.54 0.61

150 and 581 Cancer of oesophagus and cirrhosis 0.37 0.38

150 and 307-322 Cancer of oesophagus and ‘‘ alcoholism ” 0.64 0.76

1 p 5.001. p p .Ool<p<.Ol.

153

154

CANCER OF THE OESOPHAGUS

4 FIGURE 1 Mortality from “ alcoholism ” in France, by diparternent l.

4 FIGURE 2 Mortality from cancer of oesophagus in France, by dipartement l.

FIGURE 3 Mortality from cirrhosis of liver in France, by dkpartement ’.

DISCUSSION

The correlation previously described between oesophageal cancer mortality and mortality from “ alcoholism and cirrhosis ” is the reflection of a very high correlation with “acute or chronic alcoholism ” and of a much lesser correlation with cirrhosis. The implications are that the type of drinking (spirits) that leads to ‘‘ acute or chronic alcoholism ” is probably more closely related to cancer of the oesophagus than the type of drinking that leads to liver cirrhosis (beer and wine). This is in line with the findings of Wynder and Bross (1961). One may further speculate as to the meaning of this association. It may be

considered that the mechanism by which the consumption of alcohol “ produces ” or “ helps in the production o f ” oesophageal cancer must be closer to the way in which alcohol produces lesions of the central nervous system than to that in which it produces the progressive deteriora- tion of liver tissue resulting in cirrhosis.

Since neuro-psychiatrists consider that nervous lesions may be attributed to chemicals diluted in the spirits as well as to the alcohol itself, the same reasoning may apply to oesophageal cancer:

Annual rates per 100,000 population, 1960-63, in males aged 45-64 years. Numbers in the map are the “ code ” numbers of the dipartements.

155

TUYNS

120-

100-

I

0 I

y 80-

60- Q

LO-

20-

either concentrated alcohol or some carcinogenic substance diluted in it may be responsible for tumour growth. In this respect, the scatter dia- gram (Fig. 4) is particularly meaningful : there is n o example of a dtpartement with a high rate for oesophagus cancer without a simultaneously high rate for alcoholism, as if a high level of alcoholism were a necessary condition for developing a great number of cases of oesophageal cancer. It is not the sole condition though, since in dtpartements like Ardennes, Haute-Savoie, and Savoie, there is no increased rate for oesophagus cancer in spite of a high rate for alcoholism. This pattern is consistent with the hypothesis that the necessary vehicle for the carcinogen would be concentrated alcohol, while the carcinogen would be present in certain spirits (those mainly used in the west of France) and not in others (those used in Savoie o r in Ardennes). All this, of course, is speculative, but not unreasonable. It does not conflict with what has been recently proposed by research workers studying carcinogenesis in experimental animals. In France, advantage could be taken of the remarkable concentration of cancer of the oesophagus in certain areas to further study the role of alcohol in this disease.

CORRELATION BETWEEN OESOPHAGEAL CANCER MORTALITY A N D “ALCOHOLISM ” MORTALITY

[ N 88 FRENCH DEPARTEMENTS

.

56

22 29

1.4 7L 0 8 ~ ~ 3 * 3 5

050 61

53

1 I I I I

CANCER OF OESOPHAGUS

~~

I 20 LO 60 80 100 120

FIGURE 4 Annual mortality rates per 100,000 in males aged

45-64 years, 1960-63. Numbers in the graph are the “ code ” numbers of the corresponding departements.

CANCER DE L’CESOPHAGE

Des dudes prtctdentes ant montrh une corrhlation entre la mortalit6 par cancer de l’esophage et la mortalitt par alcoolisme et cirrhose du foie. Cette corrtlation est en fait plus importante avec la premiPre qlc’avec la seconde; comme les d i c h par ‘‘ al- coolisme ” se rapportent surtout aux buveurs d’alcools distillhs, cette corrtlation pourrait indiquer que c’est pour cette cat torie de buveurs que le risque de cancer de l’asophage est le plus grand. La distribution observte de la relation entre alcoolisme et cancer de I’esophage est compatible avec l’hypothkse que la consommation d’alcool distill6 est une condition nkcessaire mais non sufisante pour le dhveloppement du cancer de I’aso- phage.

REFERENCES

AUBENQUE, M. F., and DAMIANI, P., Quelques SCHWARTZ, D., FLAMANT, R., LELLOUCH, J., and donnees statistiques sur I’alcoolisme. Ses incidences DENOIX, P. F., Alcool et Cancer. Resultats d’une sur la mortalitk. Etudes statistiques de I‘INSEE, Gtude retrospective. Revue francaise d’Etudes 2, 13-23 (1956). cliniques et biologiques, Vll, 6, 590-604 (1962).

LASSERRE, O., Etude de pathologie gkographique sur la

Medecine. Facult6 de Mkdecine de Paris (1963). LASSERRE. 0.. FLAMANT. R., LELLOUCH. J.. and

u/coo/-cancer. Thbse pour le Doctorat en World Organization. Of the inter- national Statistical Classification of Diseases, In- juries and Causes of Death. WHO, Geneva (1957).

SCHWARTZ,.D., Alcool.et cancer (Etude.de patho- logie gkographique portant sur les Dtpartements francais). Bulletin de I‘INSERM, 22, 53-60 (1967).

WYNDER, E. L., and BROSS, I. J., A study of aetio- logical factors in cancer of the oesophagus. Cancer, 14, 389-413 (1961).

156