Tobacco type and risk of squamous cell cancer of the oesophagus in males: a French multicentre case-control study

Guy Launoya, Chantal Milanb, Jean Faivreb, Patrice Pienkowskic and Marc Gignouxa

a Registre des Cancers Digestifs du Calvados (CJF INSERM No 9603), Caen, France.
b Registre des Cancers Digestifs de Côte d'Or (CRI INSERM No 9505), Dijon, France.
c Registre des Cancers Digestifs de Haute-Garonne, Toulouse, France.

Reprint requests to: Guy Launoy, CJF INSERM No 9603, Faculté Médecine CHU, Caen, France.


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background The association between tobacco smoking and oesophageal cancer is well established. However, some major questions remain unanswered such as the importance of kind of tobacco and smoke inhalation. The aim of this study was to investigate the effect of each kind of tobacco on the risk of squamous cell cancer of the oesophagus in men and to test whether the effect of kind of tobacco is similar whatever the sub-site of cancer. Tobacco consumption was assessed by the number of years of consumption and time since quitting.

Methods We conducted a multicentre case-control study in three university hospitals in France (Caen, Dijon, and Toulouse). From 1991 to 1994, 208 cases and 399 controls, all male, were selected. During the interview, the subject's entire tobacco history was recalled, noting each type of tobacco consumed throughout life.

Results Strong tobacco, dark tobacco and non-filter-tipped cigarettes were associated with an increase in risk whatever the adjustments, whilst light, filter-tipped cigarettes and mild tobacco were not. Hand-rolled cigarettes were more strongly associated with risk than manufactured cigarettes. The effect of hand-rolled cigarettes appeared stronger for the lower third whilst those of strong cigarettes and dark tobacco appeared stronger for the upper third of the oesophagus. The effect of inhaling was confined to the upper third.

Conclusions Our results, emphasizing the role of dark tobacco, hand-rolled cigarettes, strong cigarettes and non-filter-tipped cigarettes are in line with previous publications. Moreover, they suggest that the mechanism underlying the tobacco effect could be different according to the sub-site of cancer.

Keywords Oesophagus, cancer, case-control study, tobacco

Accepted 28 May 1999


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The association between tobacco smoking and oesophageal cancer is well established. However, some major questions remain unanswered, such as the importance of kind of tobacco and smoke inhalation. A few studies have been published but their conclusions have often been limited by several factors. Firstly, each study focused on a particular characteristic of tobacco: pipe, hand-rolled or manufactured cigarettes,1 dark or blond tobacco,2 nicotine or tar yield3 or menthol cigarettes.4 Secondly, most of them used only daily or weekly current mean intake as the exposure measure for tobacco when it has been recently suggested that duration of exposure could be a better exposure measure than mean intake.5 Thirdly, squamous cell carcinomas and adenocarcinomas were not distinguished. The aim of this study was to investigate the effect of each kind of tobacco on risk of squamous cell cancer of the oesophagus in men and to test whether the effect of kind of tobacco is similar whatever the sub-site of cancer. Tobacco consumption was assessed by the number of years of consumption and time since quitting.


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The study was conducted between 1991 and 1994 in the university hospitals of Caen (Normandy, Calvados), Dijon (Burgundy, Côte d'Or) and Toulouse (Midi-Pyrenées, Haute-Garonne). Eligible cases were males aged <85 years admitted to one of these hospitals between January 1991 and April 1994 with histologically proven incident squamous cell carcinoma of the oesophagus. Adenocarcinoma of the oesophagus was excluded from the study due to expected differences in risk factors. During this period, 223 cases were identified. Four cases left the hospital before the dietary interview, six were physically or mentally incapable of being interviewed, and five refused to be interviewed. Finally, 208 cases were included.

The control group consisted of 399 males, matched for hospital and age, admitted during the same period to the rheumatology or orthopaedic departments for osteoarthritis (n = 229), lumbago or sciatica (n = 127), or to the eye department (n = 43). These departments were chosen because the distribution of age of patients was similar to that of the cases. Patients hospitalized for trauma, and those with experience of cancer or pathologies related to alcohol or tobacco were excluded. No control refused to participate.

Data regarding alcohol, tobacco and diet were collected from both cases and controls in face-to-face, 2-hour interviews which were conducted by seven specially trained dieticians (four in Caen, two in Dijon and one in Toulouse) in a special single room with no family members present. Dieticians also coded the data and calculated mean weekly intakes. The collecting and coding methods for drinking and dietary habits are detailed in previous reports.6 During the interview, the subject's entire smoking history was recalled for each brand of tobacco consumed throughout life. Up to four distinctive periods were recorded for each kind of tobacco if a change in smoking habits made it necessary. Within each period, mean weekly intake and the subject's age at the beginning and end were recorded. A special six-digit code was allocated to each brand of tobacco allowing us to group together tobacco according to the way of smoking (manufactured cigarette, hand-rolled cigarette, cigar, pipe), type of tobacco (blond, dark), nicotine yield (light cigarettes <15 mg; strong cigarettes >15 mg) and use of filter for cigarettes. Information on the type of tobacco, existence of filter and nicotine yield were obtained from SEITA (French producers national society) and consumers associations. Nicotine yield remained unknown for 14% of brands. Questions about depth of inhalation were confined to current consumption or the latest period of consumption for ex-smokers.

Since the years of consumption (number of years during which consumption was not equal to zero), and number of years since quitting were shown to be the most appropriate exposure measure for tobacco in a previous analysis,5 these variables were calculated for each group of tobacco. Their effect on the risk of oesophageal cancer was then tested for each group of tobacco in unconditional logistic regression estimating odds ratios (OR) and 95% CI.7 Since other previous analyses have shown that oesophageal cancer risk was associated with special alcoholic drinks and food groups,6,8 adjustment was made for these variables. The effect of each kind of tobacco was tested using logistic regression in two different models: in model 1, adjustments were done only for age and interviewer; in model 2, additional adjustments were done for sociodemographic factors, total alcohol intake, types of beverage which had an effect on the risk, i.e. beer, aniseed aperitifs, hot calvados and whisky; and food groups which had an effect on the risk, i.e. fish, oleaginous fruits, vegetables and butter.

As certain groups of tobacco were strongly correlated, forward step-wise procedures were used to construct multivariate models of risk eliminating variables which no longer had any effect when adjusted for the others.


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Tables 1 and 2GoGo show, respectively, the distribution of number of years of consumption and the number of years since quitting for cases and controls according to the kind of tobacco. Whatever the measure of consumption, without any adjustment, light tobacco, mild cigarettes and filter-tipped cigarettes were not linked with an increase in the risk of cancer unlike all other kind of tobacco. Concerning mild tobacco, the number of years of consumption was even higher for controls than for cases. Table 3Go shows the effect of the number of years of consumption of tobacco on the risk of the cancer of the oesophagus in the two models described above. Taking the overall view, the correlations between tobacco consumption and potential confounding factors, such as sociodemographic characteristics, alcoholic drinks and food group consumption, were not high enough, as shown in Table 4Go, to affect the link between tobacco and cancer risk, so that the different models yielded similar results.


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Table 1 Distribution of number of years of tobacco consumption according to the kind of tobacco for 208 cases of oesophageal cancer and 399 controls
 

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Table 2 Distribution of number of years since quitting according to the kind of tobacco for 208 cases of oesophageal cancer and 399 controls
 

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Table 3 Number of years of tobacco consumption and risk of oesophageal cancer according to the kind of tobacco
 

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Table 4 Kind of tobacco consumptiona and oesophageal cancer in a French multicentre case-control study: correlation with sociodemographic characteristics, alcoholic drinks and food groups in controls
 
Despite the positive correlation with total alcohol consumption and hot calvados consumption—which is strongly linked with the risk of oesophageal cancer—hand-rolled cigarettes were significantly associated with risk of oesophageal cancer whatever the adjustments. Moreover, hand-rolled cigarettes were even more strongly significant than manufactured cigarettes which fell below statistical significance after adjustment for dietary factors and sociodemographic characteristics. Strong and non-filter-tipped cigarettes, despite the positive correlation with total alcohol consumption, were associated with an increase in risk in all models, whilst light and filter-tipped cigarettes were not. Similarly, dark tobacco, which was most firmly linked with total alcohol consumption, was strongly associated with an increase in risk in all models, whilst blond tobacco, positively linked with the level of education, was associated with a decrease in risk but not in a significant way after adjustments. Pipe smoking was not associated with the risk of oesophageal cancer whatever the adjustments made. Even if pipe smokers were grouped together whatever the duration of consumption, the OR for consumers (versus non-consumers) was not significant (1.03 [95% CI : 0.43–2.46] in model 2). Too few people smoked cigars to enable their study.

All results were similar when variables were transformed into dichotomous variables (consumers/non-consumers). Since blond tobacco and filter use has emerged recently, the influence of mean weekly consumption over the last 10 years was also tested for these two kinds of tobacco. It was not significant. When smoke inhalation was tested among smokers, it was never associated with an increase in risk, whatever the adjustments.

Table 5Go shows that results were similar when time since quitting was used as exposure measure instead of number of years of consumption (Table 3Go). The only difference concerned pipe smoking whose effect tended to be significant after all adjustments (P = 0.08 in model 2) and became significant when variables were transformed into dichotomous variables (non-current smokers/current smokers) (ORa = 0.13 [95% CI : 0.02–0.82]).


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Table 5 Number of years since quitting and risk of oesophageal cancer according to the kind of tobacco
 
As expected, there were some high correlations between several kinds of tobacco for the number of years of consumption (Table 6Go). The pattern of correlations with the number of years since quitting was similar and thus is not shown. When the effect of each kind of tobacco was studied taking into account the effect of other kinds after all adjustments in model 2, the stepwise logistic regression yielded different results depending on the way of measuring tobacco consumption. Considering the number of years of consumption, only dark tobacco (P < 0.001) and hand-rolled tobacco (P < 0.05) had an independent effect on the risk. Considering the number of years since quitting, only dark tobacco (P < 0.01) and strong cigarettes (P < 0.05) were kept in the final model.


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Table 6 Correlation between the number of years of consumption of different kinds of tobacco for controls (N = 399)
 
Table 7Go shows the effect of each tobacco group on the risk of the cancer of the oesophagus, using the adjustments of model 2, according to cancer sub-site. Since the number of cases was small for a given sub-site, tobacco consumption was treated as dichotomous variables (consumers/never consumers). The effect of hand-rolled cigarettes appeared stronger for the lower third of the oesophagus whilst that of strong cigarettes and dark tobacco appeared stronger for the upper third. A significant effect of inhaling (tested among smokers) was found only for the upper third with an OR of 1.56 (95% CI : 1.07–2.28).


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Table 7 Tobacco consumption and riska of oesophageal cancer according to the kind of tobacco and the sub-site of cancer
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Our results show that the well-established link between the risk of oesophageal cancer and tobacco depends greatly on the kind of tobacco and the sub-site of cancer.

In such a hospital-based study, results could be affected by selection bias. Concerning cases, this bias is probably weak since the treatment of oesophageal cancer is centralized, i.e. confined to specialized units. Concerning controls, all patients with pathologies related to alcohol and tobacco consumption were excluded. All controls selected agreed to participate.

For the whole oesophagus, our results emphasize the role of hand-rolled cigarettes, dark tobacco, strong cigarettes and non-filter-tipped cigarettes and are in line with previous publications, the only disagreement being the lack of effect for pipe smoking.

Several studies have suggested that dark tobacco carries a higher risk than blond tobacco for oesophageal cancer,2,9 consistent with results for cancer of larynx, pharynx and mouth10–12 and for lung cancer.13,14 According to our analysis, kind of tobacco (dark or blond) could be the most important characteristic of tobacco with regard to the risk of oesophageal cancer, whatever the measure of consumption (time since quitting or number of years of smoking). Esteve suggested that the finding that blond tobacco contains lower levels of polycyclic aromatic hydrocarbons than dark tobacco is the chief explanation for this difference.9 However, N-nitroso compounds seem to be more target organ specific for the oesophagus than polycyclic aromatic hydrocarbons.

Concerning hand-rolled cigarettes, our results are in agreement with previous studies concerning oesophageal cancer,1,15,16 and replicate results for cancer of larynx, pharynx and mouth.10 Its effect remained significant after all adjustments suggesting a true effect even if this way of smoking is correlated with other customs markedly associated with an increase in risk, such as hot calvados drinking and a diet deficient in vegetables. The lack of an independent effect of hand-rolled cigarettes on the risk after adjustment for other types of tobacco when consumption is assessed by the time since quitting could be due to the dramatic decrease in the use of this kind of tobacco over time.17

Whether strong cigarettes carry a higher risk than light tar cigarettes has been investigated for oesophageal cancer less often than for other sites such as lung. Our results reinforce those of a recent Italian study suggesting that tar yield is a strong determinant of the risk of oesophageal cancer although those data were not derived from a detailed history but concerned only the brand smoked for the longest time.3

Concerning filter use, which seems to de relatively protective in our study, previous results are conflicting. Brown found no effect of filter use whereas Estève assessed the relative protection given by filters, partly confounded by blond tobacco use, to be 0.19 (95% CI : 0.05–0.76).9,18

According to our results, number of years of pipe smoking has no effect on the risk whilst other studies have shown a higher relative risk for pipe smokers compared to cigarettes smokers19,20 and even to hand-rolled cigarettes.1 This conflict could be explained by the difference in consumption assessment which was recent consumption in these studies and duration of consumption in ours. This agrees with the emergence of an effect for pipe smoking when time since quitting is considered instead of duration of consumption. Moreover, in most of the studies, relative risk was assessed for pipe smoking exclusively while in our study pipe smoking, taking other tobacco smoking into account, was used. However, the failure to see any association between pipe smoking and cancer risk is most likely to be due to the small numbers of pipe smokers in our study.

Results according the sub-site of cancer are very informative. The effect of smoke inhalation was confined to the upper third whilst the effect of hand-rolled cigarettes appeared to be stronger for the lower third of the oesophagus. These results suggest that the mechanism underlying the tobacco effect could be different according to the sub-site of cancer. For the upper third, as for cancers of the larynx and pharynx, the carcinogenic agents seem to be mainly carried by smoke. For the other two-thirds, a substantial part of carcinogenic effect could be due to the swallowing of small pieces of tobacco. This hypothesis, previously proposed by Schwartz21 is consistent with Nandakumar et al.'s22 recent results showing that the effect of tobacco chewing was confined to the lower third of the oesophagus.


    References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
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