Department of Epidemiology, School of Public Health, Catholic University of Leuven, Leuven, Belgium.
Reprint request to: Prof. Hugo Kesteloot, Department of Epidemiology, Kapucijnenvoer 33, B-3000 Leuven, Belgium. E-mail: hugo.kesteloot{at}med.kuleuven.ac.be
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Abstract |
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Methods Sex-specific LCM data, mostly around 1993 and fish consumption data for 10 periods 19611994 in 36 countries were obtained from WHO and FAO, respectively.
Results A significant inverse correlation exists between log fish consumption and LCM rate in 9 out of the 10 time periods (r = 0.34 to r = 0.46, P = 0.044 to P = 0.005). After adjusting for smoking and other confounders, log fish consumption (% of total energy [% E]) was inversely and significantly associated with LCM rate (per 100 000 per year) in all 10 time periods (ß = 26.3 to ß = 36.7; P = 0.0039 to P < 0.0001). The stratified analysis showed that this inverse relation was significant only in countries with above median level of smoking (>2437 cigarettes/adult/year) or animal fat minus fish fat consumption (22.4% E). An increase in fish consumption by 1% E was calculated to reduce mean male LCM rate of the populations examined in the age class of 4574 years by 8.4%. In women, no significant relation between fish consumption and LCM could be established.
Conclusions Fish consumption is associated with a reduced risk from LCM, but this possible protective effect is clear-cut only in men and in countries with high levels of cigarette smoking or animal fat consumption.
Keywords Animal fat, cigarette smoking, fish consumption, lung cancer mortality
Accepted 7 February 2000
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Introduction |
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Materials and Methods |
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The data of fish, animal fat, vegetable and fruit consumption were derived from the Food Balance Sheets, Food and Agriculture Organization (FAO) for 10 periods (19611963, 19641966, 19691971, 19741976, 19791981, 19821984, 19841986, 19871989, 19891991 and 19921994).12 The dietary and mortality data were obtained from the same 36 countries, with missing dietary data for Singapore for the last three periods. Animal fat includes fish fat in the FAO data set. To better adjust for the confounding effect of animal fat on the relation between fish consumption and LCM, a new variable, animal fat minus fish fat (AFFF), was created. Fish, AFFF, vegetable and fruit consumption were expressed as per cent of total energy (% E), because % E is more appropriate than absolute units for FAO's food consumption data.13 Cigarette consumption data (n/adult/year) in 19701972, 19801982 and 19901992 were obtained from WHO.1 The Czech Republic and Hong Kong have missing data in these three periods. Cigarette consumption data from these two countries (areas) in 1970 and 1985 were used instead.14
Statistical analysis
The normality of the distribution of the data used was tested prior to the analysis. Because of the skewed distribution of fish consumption in the 10 time periods considered, the data were transformed by natural logarithm, resulting in a normal distribution. The Pearson correlation analysis was made between fish consumption and LCM rate. Multiple linear regression analysis was performed with LCM rate as a dependent variable and fish, AFFF, vegetable, fruit and cigarette consumption as independent variables. All independent variables were retained in the regression equations irrespective of their significance levels. In the multivariate models, AFFF, vegetable and fruit consumption data were obtained from the same period as the fish consumption. Mean cigarette consumption of 19701972, 1980 1982 and 19901992 was calculated and then introduced into the multivariate models. For the Czech Republic and Hong Kong, the mean cigarette consumption of 1970 and 1985 was used for substitution. To explore whether the relation between fish consumption and LCM varies with the amount of cigarette and AFFF consumption among all the countries selected, the interaction terms between fish and cigarette consumption and between fish and AFFF consumption were examined in multiple regression models which only include the interaction term and its constituting variables. Based on the findings of the interaction analysis, stratified analyses were performed between countries with low and high levels of cigarette smoking and with low and high levels of AFFF consumption in the same manner as in the analysis with all countries included. The only difference is that vegetable and fruit consumption was excluded from the models, as only 18 observations were available in each group. Countries with low and high levels of smoking were defined as the countries with cigarette consumption < and > the median (2437 cigarettes/adult/year) of mean cigarette consumption of 19701972, 19801982 and 19901992, while countries with low and high levels of AFFF consumption as the countries with AFFF < and > the median (22.4 % E) of mean AFFF of the 10 periods considered. The classification of countries by using the mean consumption over a prolonged period of time is more relevant in view of the dynamic nature of the exposures which can change during the period of observation. The number of countries was 36 in the analysis including all countries and 18 in the stratified analysis. Because of missing data of fish, AFFF, vegetable and fruit consumption in Singapore in the last three periods, the number of countries examined in these periods was one less than that in other periods. Significance level was P < 0.05 (two-tailed). All analyses were performed with the statistical package SAS (SAS Institute, Inc., Cary, North Carolina) for 10 periods and for both sexes. Because no significant relation between fish consumption and LCM rate in women was detected in any of the analyses performed, only the results for men are presented.
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Results |
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Discussion |
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To date, most studies concerning diet and lung cancer have concentrated on the relation of dietary intake of fat, cholesterol, vegetable, fruit and vitamin A to lung cancer risk.38,1519 Epidemiological evidence on the relation between fish consumption and lung cancer risk is scarce. The findings obtained so far, mostly from a case-control approach, are rather controversial. The possible protective effect of fish consumption on LCM observed here is consistent with the results of case-control studies from Hong Kong10 and Australia.20 The beneficial influence of fish intake on lung cancer risk was also detected in a Norwegian cohort of 13 785 men and 2928 women followed up for 11.5 years17 and in a case-control study in Kerala, India,11 although the results from these studies did not attain statistical significance. No significant relation between fish consumption and LCM was found in a multiethnic case-control study in Hawaii.3 The relative risk of lung cancer increased with the ascending quartiles of fish intake (P for trend < 0.01) in a Chinese mining community.21 However, caution should be given to this finding because fish intake, both in cases and controls, was very low in the latter study (<1/month).21
The mechanisms by which fish consumption appears to protect against lung cancer remain unclear. N-3 polyunsaturated fatty acids, abundantly present in fish, have been shown to possess an anti-inflammatory effect.2224 Fish intake was reported to protect cigarette smokers against chronic obstructive pulmonary disease25,26 and the deterioration of lung function.27 A case-control study in north-east China showed that prior chronic bronchitis and/or emphysema significantly contributed to the risk of lung cancer.28 However, whether this anti-inflammatory property of fish intake is partly responsible for its protective effect on lung cancer risk still needs to be elucidated. Some studies have found that the intake of animal fat, particularly, saturated fat, is associated with an increased risk of lung cancer.3,16,29 Previous findings have disclosed that animal fat interacts with cigarette smoking to promote the occurrence of lung cancer.30 It is likely that fish intake partially generates its beneficial influence on LCM by means of substituting for saturated fat intake.31 Therefore, it is reasonable to assume that the protective effect of fish consumption on lung cancer risk would be apparent only if its challenge, such as cigarette smoking and animal fat intake, are sufficiently strong and may explain why fish consumption confers its protective effect on LCM only in countries with high levels of cigarette smoking or AFFF consumption. Fish oil has been reported to inhibit rectal mucosal cell proliferation in subjects with sporadic adenomatous colorectal polyps32 and the growth of human breast carcinoma maintained in athymic nude mice.33
The observations of the present study aid clarification of some perplexing epidemiological phenomena. Hungary and Iceland are two countries with high levels of cigarette consumption and animal fat intake, but the LCM rate in Hungarian men is approximately 3.4 times that in Iceland. The major dietary difference between these two populations is that fish consumption is much higher in Iceland. Cigarette smoking in Japan is among the highest in the world, but its LCM rate is among the lowest. High fish consumption, coupled with a low animal fat intake, may offer a partial explanation for this paradoxical phenomenon (Table 1).
A significant relation between fish consumption and LCM was not found in women in the present study. The prevalence and amount of cigarette smoking is lower in women than in men in nearly all populations in the world.1,14 The actual smoking habits of women are of recent origin and their cigarette consumption is generally increasing.1,14 The time lag of lung cancer may thus explain the lack of a significant association in women.30
The findings of epidemiological studies should be universally applicable before a possible causal relationship can be considered. In the present study, all countries with relatively reliable data were included and no country was excluded as an outlier. The decision for inclusion was made before the results of the analysis were known. The relation between fish consumption and LCM was examined in 10 periods over a span of about 30 years. Linking LCM to different intervals of fish exposure, instead of a single one, is a relevant approach to reduce the possibility of obtaining a chance finding. Cigarette consumption (n/adult/year) was significantly and positively associated with male LCM (per 100 000 per year) in all periods (ß = 0.026 to ß = 0.034; P = 0.045 to P = 0.006) except for 19741976 (ß = 0.025, P = 0.053). This result suggests the reliability of the data used for the analysis.
Several limitations inherent in this study should be taken into account. The ecological approach covers exposure to disease on a population basis. Thus, our findings are subject to the ecological fallacy.34 The FAO data only reflect the overall pattern of food consumption of a whole population, without considering age and sex differences in dietary intake. The precision of diagnosis, the level of medical treatment and the completeness of death registration vary with the countries selected,2 which may weaken the reliability of the mortality data from WHO. These measurement errors contribute to regression dilution bias which tends to attenuate the true regression coefficients of fish consumption versus LCM.35 The data used in this study are far from optimal but are the best available for examining the relation between fish consumption and LCM in a large number of populations worldwide.
The present study suggests that fish intake protects against lung cancer, confirming findings from some case-control studies.10,20 The inverse significant relation between fish consumption and LCM was found only in countries with high levels of cigarette smoking or animal fat consumption. This observation has not been reported previously. A growing body of epidemiological evidence has shown that fish intake is also protective against cardiovascular disease,3639 chronic respiratory disease,25,26 rheumatoid arthritis,40 ulcerative colitis41 and all-cause mortality.39,42 In view of the beneficial effect of fish intake on disease risk and the possibility of a dietary insufficiency of n-3 polyunsaturated fatty acids in the Western diet,43 it is inferred that increasing the amount of fish consumption could decrease the mortality of lung cancer and other related diseases, especially in populations with high levels of cigarette consumption and animal fat intake. More studies are needed to confirm these findings and to elucidate the mechanisms underlying the possible protective effect of fish intake on lung cancer risk.
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Acknowledgments |
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References |
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