BRIEF COMMUNICATION
Distribution of Smoking and Its Association With Lung Cancer: Implications for Studies on the Association of Fat With Cancer James R. Hebert,* Geoffrey C. Kabat
Unlike findings from ecological studies (7,2), findings from case-control and follow-up studies have indicated that dietary factors, especially fat, are only weakly associated with cancers of the breast (3-7), colon (8-10), and prostate (11-15). Nutritional homogeneity—or the tendency of nutrients to be narrowly distributed within populations—may explain this discrepancy (16-18). In ecological studies conducted worldwide, dietary fat is the nutrient that has shown the strongest associations with cancer risk (12,19). In 90% of 153 countries on which there are data, the mean values indicate that fat constitutes 1l%-42% of all calories consumed (16,1720). In the United States, by comparison, 90% of the adult population consume between 29.5% and 43.5% of their total calories
as fat (2122). To observe the effect of a limited range of exposure on a known strong risk relationship, we chose the relationship between smoking and lung cancer because it is one of the strongest, and most consistent, in epidemiologic data. We used a case-control database to test the effect on the odds ratio of limiting the distributions of cigarette smoking in the study population. We constrained the distribution of tobacco smoking to a range proportional to that of the dis872
tribution of calories as fat in the United States, relative to the world's distribution of calories as fat.
Methods In earlier work, we observed a wide distribution of calories as fat internationally as compared with the United States (19). The maximum value of calories as fat for 64 countries on which we had both food disappearance and cancer mortality data was 42.9%, and the mean value was 24.0% (2023). The National Center for Health Statistics' intraperson-adjusted range of calories as fat for the United States was 25.6%46.4% (2122), corresponding to approximately the 55th and the 100th percentile values, respectively, of the 64-country mean distribution. To illustrate the effect of limiting the distribution of the risk factor on estimation of a known risk factor-cancer relationship, we used a hospital-based case-control study database. This database has been used for numerous analyses, and its procedures for case-control selection and data collection have been reported elsewhere (24). The data used for these analyses were obtained from 812 men and 588 women with histologically confirmed lung cancer and 1719 men and 1238 women with other diagnoses. These control diagnoses included non-cancers, benign neoplasms, and cancers thought not to be related to exposure to tobacco smoke. Control patients were matched to case patients on age (±5 years), sex, hospital, and time of interview (±2 months). To maintain clear and unambiguous contrasts, we excluded all ex-smokers from analyses. To correspond with the United States versus world fat data, we truncated the distribution of cigarettes smoked per day at the 55th percentile value. In addition to analyses that included both current smokers and subjects who have never smoked, we conducted the full-versus-truncated (at the 55th percentile) analyses for current smokers only. The distribution of smoking in this group is approximately gaussian in nature (79). The results, based on analyses that included subjects who have never smoked, are presented in simple tabular form.
We chose not to adjust for other risk factors in analyses for three major reasons: 1) cigarettes per day (dose) is the dominant risk factor for lung cancer, 2) by matching on age, we accounted for age and, indirectly, for duration of smoking (the second most important tobacco-related risk factor), because most people begin smoking at approximately the same age (late adolescence or early adulthood); and 3) by picking an example with such a strong association, we did not have to be unnecessarily concerned with distracting issues, such as effect modification or confounding.
Results Tables 1 and 2 show the results for men. For the full distribution (Table 1), a strong incremental risk was found with an increase in cigarettes smoked per day. For the truncated distribution (Table 2), a very slight, nonsignificant, increase in risk was found in the 21-30 cigarettes smoked per day category, in comparison with smokers in the 15-20 cigarettes smoked per day category. Only slight increases in risk were found in the 31-40 cigarettes smoked per day category, and moderate increases in risk were found in the 41+ cigarettes smoked per day category. The chi-square test for trend was drastically reduced to 16.63. Results based only on current smokers indicated a similar reduction from an odds ratio of 3.37 (95% confidence interval [CI] = 2.54-4.48) across extreme quartiles of the full current-smoker distribution (chi-square for trend = 58.68)
Received December 1, 1990; revised March 8, 1991; accepted March 18, 1991. Supported by a grant from the Herrick Foundation (J. R. Hebert) and by Public Health Service program project grant CA-32617 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. J. R. Hebert, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Mass. G. C. Kabat, Division of Epidemiology, American Health Foundation, New York, NY. *Correspondence to: James R. Hebert, ScD, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655.
Journal of the National Cancer Institute
Discussion
Table 1. Smoking and lung cancer in men: full distribution*
Never smokers
1-19 CPD
Current smokerst 20-29 CPD
30+CPD
88 853 1.00
99 250 3.84 (2.69-5.47)
223 259 8.35 (6.26-11.12)
402 357 10.92 (8.42-14.15)
No. of case patients No. of control patients Odds ratio (95% CI)
•Current and never smokers. tCPD = cigarettes per day. Chi-square test for linear trend = 409.53.
Table 2. Smoking and lung cancer in men: truncated distribution*
15-20 CPD No. of case patients No. of control patients Odds ratio (95% CI)
234 293 1.00
Current smokerst 21-30 CPD 31-40 CPD 129 153 1.04 (0.77-1.40)
174 150 1.45 (1.11-1.71)
41+CPD 123 83 1.86 (1.37-2.51)
•Taking the 55th to the 100th percentile of the full distribution. tCPD = cigarettes per day. Chi-square test for linear trend = 16.63.
to an odds ratio of 1.77 (95% CI = 1.262.50) in the truncated distribution (chisquare for trend = 9.54). Tables 3 and 4 show the results for women. For the full distribution (Table 3), a stronger incremental risk was found for women than for men. With the loss of the lowest 55% of the distribution, we found sparse data in the highest exposure category (41+ cigarettes smoked per day), resulting in a reversal of the pattern of increasing risk observed by
amount smoked in the middle two quartiles relative to the lowest exposure category (15-20 cigarettes smoked per day). The results for current women smokers showed a more severe reduction than we observed for men, from an odds ratio of 5.30 (95% CI = 3.69-7.62) across extreme quartiles of the full currentsmoker distribution (chi-square for trend = 59.63) to an odds ratio of 1.20 (95% CI = 0.68-2.13) in the truncated distribution (chi-square for trend = 1.13).
Table 3. Smoking and lung cancer in women: full distribution*
Never smokers
1-19 CPD
Current smokerst 20-29 CPD
30+CPD
97 868 1.00
85 155 4.91 (3.40-7.08)
166 115 12.92 (9.56-17.45)
220 100 19.69 (14.86-26.07)
No. of case patients No. of control patients Odds ratio (95% CI)
•Current and never smokers. tCPD = cigarettes per day. Chi-square test for linear trend = 501.89. Table 4. Smoking and lung cancer in women: truncated distribution*
15-20 CPD No. of case patients No. of control patients Odds ratio (95% CI)
174 138 1.00
Current smokerst 21-30 CPD 31-40 CPD 113 60 1.49 (1.06-2.11)
•Taking the 55th to the 100th percentile of the full distribution. tCPD = cigarettes per day. Chi-square test for linear trend = 13.37.
Vol. 83, No. 12, June 19, 1991
98 33 2.36 (1.65-3.37)
41+CPD 34 15 1.80 (1.06-3.04)
Dietary fat is the nutrient most strongly related to cancer risk in ecological data (12). The lack of effect observed in analytic studies may be due to the absence of low levels of fat exposure in populations from which study samples are drawn (3-17). Many laboratory experiments indicate that a strong effect of fat intake on cancer risk is shown only by comparison with animals eating fewer than 25% of their calories as fat (25-27). For all practical purposes, this low fat intake is outside the range of what is observed in human populations of the United States or other western countries. The portion of the smoking distribution we analyzed was equivalent to the fraction of the world distribution of fat represented by the distribution of dietary fat in the United States. This exercise dramatically demonstrated that the toss of a large portion of the lower part of the distribution of cigarette smoking results in a striking diminution of risk estimates for lung cancer. For both men and women, we observed the strongest incremental effect of tobacco at lower doses of cigarettes smoked per day. For example, there is nearly a fourfold increase in lung cancer risk between male current smokers of 1 19 cigarettes per day and subjects who have never smoked, whereas there is less than a threefold (ie, odds ratio = 2.56) risk among smokers of 20+ cigarettes per day compared with those smoking 1-19 cigarettes per day. Among women, there is an odds ratio of 4.91 in smokers of 1-19 cigarettes per day compared with those subjects who have never smoked but an odds ratio of only 3.27 in women smokers of 20+ cigarettes per day compared with those smoking 1-19 cigarettes per day. The quantitative differences observed between the sexes may be due to a more marked effect of cigarette smoking among women (25). The nonlinearity that we observed in dose-response is not uncommon in epidemiologic studies (29^0). It is apparent that the never smokers in our study provided the largest contrast in the data. That is, the odds ratio obtained in comparing never smokers to smokers in
BRIEF COMMUNICATION 873
the second quartile of the full distribution was larger than any obtained in comparing other adjacent quartiles. By removing that portion of the distribution at lowest risk of disease, we diluted our estimates of association by forcing the analysis into the high-risk realm, in which risk relationships are most difficult to observe (37). It has been suggested that estimates of the effect of dietary fat and cancer risk in humans are attenuated in much the same way, though to a greater extent (32). Given evidence that indicates fat-cancer effects are not as linear as are smokinglung cancer effects (25-27), the loss of the lower 55% of the fat distribution may pose more serious problems for estimation of dietary fat-cancer relationships. This work points out the need to identify study groups consuming diets that lie outside the range of typical North American and European fat intake if we wish to estimate the true potential effect of dietary fat on human cancer (32 J 3).
References tors and cancer incidence and mortality in different countries, with special references to dietary practices. Int J Cancer 15:617-631, 1975 (2) CARROLL KK, KHOR HT: Dietary fat in rela-
tion to tumorigenesis. Prog Biochem Pharmacol 10:308-353, 1975 (3) WILLETT WC, STAMPFER MJ, COLDFTZ GA,
ET AL: Dietary fat and the risk of breast cancer. N Engl J Med 316:22-28, 1986 K,
WILLETT W, TRICHOP.
OULOS D, ET AL: Risk of breast cancer among
12
AL: An epidemiologic study on the association between diet and breast cancer. JNCI 78:595-600,1987 Dietary habits and breast cancer incidence among Seventh-day Adventists. Cancer 64:582-590,1989 (7) BYERS T: Diet and cancer: Any progress in the interim? Cancer 62:1713-1724, 1988 KR, ET AL: Physical activity, diet, andriskof colon cancer in Utah. Am J Epidemiol 128:989-999,1988 POTTER
JD:
Diet
and
colonic cancer. Integration of the descriptive, analytic, and metabolic epidemiology. Natl Cancer Inst Monogr 69:223-228,1985
Diet in the epidemiology of carcinoma of the prostate gland. JNCI 70:687-692, 1983 (12) FLANDERS WD: Review: Prostate cancer epidemiology. Prostate 5:621-629, 1984 (13) SNOWDON DA, PHILLIPS RL, CHOI W: Diet,
obesity, and risk of fatal prostate cancer. Am J Epidemiol 120:244-250, 1984
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(29) SCHIFFLERS E, JAMART J, RENARD V: Tobac-
Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64:598— 604, 1989
co and occupation as risk factors in bladder cancer: A case-control study in southern Belgium. Int J Cancer 39:287-292, 1987 (30) AUGUSTINE A, HEBERT JR, KABAT GC, ET
AL: Bladder cancer in relation to cigarette smoking. Cancer Res 48:4405-4408, 1988
(16) HEBERT JR, WYNDER EL: Dietary fat and the
risk of breast cancer. N Engl J Med 317:165— 166,1987 (17) WYNDER EL, HEBERT JR: Homogeneity in
nutritional exposure: An impediment in cancer epidemiology. JNCI 79:605-607, 1987 (18) WiLLETT W: Nutritional Epidemiology. New York: Oxford Univ Press, 1990
Only $9 Per Year (U.S.) or $11.25 (Foreign Address, Via Airmail)
(25) COHEN LA, CHOI K, WBSBURGER JH, ET AL:
Female-male differences in patients with primary lung cancer. 59:1825-1830, 1987
AL: Nutrition, social factors and prostatic cancer in a Northern Italian population. Br J Cancer53:817-821,1986
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Statistics Annual (Data Tapes 1980-1986). Geneva; WHO, 1985
(28) MCDUFFIE HH, KLAASSEN DJ, DOSMAN JA:
(14) TALAMINI R, LAVECCHIA C, DECARLIA A, ET
Don't Miss an Issue of the Research Resources Reporter
(23) WORLD HEALTH ORGANIZATION: World Health
Effect of varying proportions of dietary fat on the development of /V-nitrosomethylureainduced rat mammary tumors. Anticancer Res 6:215-218, 1986 (26) BIRT DF: The influence of dietary fat on carcinogenesis: Lessons from experimental models. Nutr Rev 48:1-5, 1990 (27) WEISBURGER JH: Role of fat, fiber, nitrate, and food additives in carcinogenesis: A critical evaluation and recommendations. Nutr Cancer 8:47-62, 1986
(//) GRAHAM S, HAUGHEY B, MARSHALL J, ET AL:
Reporter
Data: United States, Dietary Intake 1976-80. Vital and Health Statistics. Series 11-No. 231. DHHS Publ No. (PHS)83-1681. Washington, DC: US Govt Print Off, 1983
Smoking and adult leukemia: A case-control study. J Clin Epidemiol 41:907-914, 1988
A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Am J Epidemiol 109:132144,1978
sociation of dietary fat and lung cancer. J Nad Cancer Inst 79:631-637, 1987
Sources of variance in 24-hour dietary recall data: Implications for nutrition study design and interpretation. Am J Clin Nutr 32:25462559,1979
(24) KABAT GC, AUGUSTINE A, HEBERT JR:
(10) DALES LG, FRIEDMAN GD, URY HK, ET AL:
(19) WYNDER EL, HEBERT JR, KABAT GC: As-
1979-1981 average. Rome: FAO, 1981
(22) NATIONAL CENTER FOR HEALTH STATISTICS, CARROLL MD, ABRAHAM S, ET AL: Source
(8) SLATTERY ML, SCHUMACHER MC, SMITH
(9) MCMICHAEL AJ,
(20) FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS: Food balance sheets, (21) BEATON GH, MILNER J, COREY P, ET AL:
(6) MILLS PK, BEESON WL, PHILLIPS RL, ET AU
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(15) MILLS PK, BEESON WL, PHILLIPS RL, ET AU
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(4) KATSOUYANNI
Greek women in relation to nutrient intake. Cancer61:181-185,1988
(31) ROTHMAN KJ, POOLE C: A strengthening
programme for weak associations. Int J Epidemiol 17:955-959, 1988 (32) HEBERT JR, MILLER DR: Methodologic con-
siderations for investigating the diet-cancer link. Am J Clin Nutr 47:1068-1077, 1988 (33) ZARIDZE DG, MUIR CS, MCMICHAEL AJ:
Diet and cancer: Value of different types of epidemiological studies. Nutr Cancer 7:155— 166,1985
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Vol. 83, No. 12, June 19, 1991
875
Distribution of Smoking and Its Association With Lung Cancer: Implications for Studies on the Association of Fat With Cancer James R. Hebert,* Geoffrey C. Kabat
Unlike findings from ecological studies (7,2), findings from case-control and follow-up studies have indicated that dietary factors, especially fat, are only weakly associated with cancers of the breast (3-7), colon (8-10), and prostate (11-15). Nutritional homogeneity—or the tendency of nutrients to be narrowly distributed within populations—may explain this discrepancy (16-18). In ecological studies conducted worldwide, dietary fat is the nutrient that has shown the strongest associations with cancer risk (12,19). In 90% of 153 countries on which there are data, the mean values indicate that fat constitutes 1l%-42% of all calories consumed (16,1720). In the United States, by comparison, 90% of the adult population consume between 29.5% and 43.5% of their total calories
as fat (2122). To observe the effect of a limited range of exposure on a known strong risk relationship, we chose the relationship between smoking and lung cancer because it is one of the strongest, and most consistent, in epidemiologic data. We used a case-control database to test the effect on the odds ratio of limiting the distributions of cigarette smoking in the study population. We constrained the distribution of tobacco smoking to a range proportional to that of the dis872
tribution of calories as fat in the United States, relative to the world's distribution of calories as fat.
Methods In earlier work, we observed a wide distribution of calories as fat internationally as compared with the United States (19). The maximum value of calories as fat for 64 countries on which we had both food disappearance and cancer mortality data was 42.9%, and the mean value was 24.0% (2023). The National Center for Health Statistics' intraperson-adjusted range of calories as fat for the United States was 25.6%46.4% (2122), corresponding to approximately the 55th and the 100th percentile values, respectively, of the 64-country mean distribution. To illustrate the effect of limiting the distribution of the risk factor on estimation of a known risk factor-cancer relationship, we used a hospital-based case-control study database. This database has been used for numerous analyses, and its procedures for case-control selection and data collection have been reported elsewhere (24). The data used for these analyses were obtained from 812 men and 588 women with histologically confirmed lung cancer and 1719 men and 1238 women with other diagnoses. These control diagnoses included non-cancers, benign neoplasms, and cancers thought not to be related to exposure to tobacco smoke. Control patients were matched to case patients on age (±5 years), sex, hospital, and time of interview (±2 months). To maintain clear and unambiguous contrasts, we excluded all ex-smokers from analyses. To correspond with the United States versus world fat data, we truncated the distribution of cigarettes smoked per day at the 55th percentile value. In addition to analyses that included both current smokers and subjects who have never smoked, we conducted the full-versus-truncated (at the 55th percentile) analyses for current smokers only. The distribution of smoking in this group is approximately gaussian in nature (79). The results, based on analyses that included subjects who have never smoked, are presented in simple tabular form.
We chose not to adjust for other risk factors in analyses for three major reasons: 1) cigarettes per day (dose) is the dominant risk factor for lung cancer, 2) by matching on age, we accounted for age and, indirectly, for duration of smoking (the second most important tobacco-related risk factor), because most people begin smoking at approximately the same age (late adolescence or early adulthood); and 3) by picking an example with such a strong association, we did not have to be unnecessarily concerned with distracting issues, such as effect modification or confounding.
Results Tables 1 and 2 show the results for men. For the full distribution (Table 1), a strong incremental risk was found with an increase in cigarettes smoked per day. For the truncated distribution (Table 2), a very slight, nonsignificant, increase in risk was found in the 21-30 cigarettes smoked per day category, in comparison with smokers in the 15-20 cigarettes smoked per day category. Only slight increases in risk were found in the 31-40 cigarettes smoked per day category, and moderate increases in risk were found in the 41+ cigarettes smoked per day category. The chi-square test for trend was drastically reduced to 16.63. Results based only on current smokers indicated a similar reduction from an odds ratio of 3.37 (95% confidence interval [CI] = 2.54-4.48) across extreme quartiles of the full current-smoker distribution (chi-square for trend = 58.68)
Received December 1, 1990; revised March 8, 1991; accepted March 18, 1991. Supported by a grant from the Herrick Foundation (J. R. Hebert) and by Public Health Service program project grant CA-32617 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. J. R. Hebert, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Mass. G. C. Kabat, Division of Epidemiology, American Health Foundation, New York, NY. *Correspondence to: James R. Hebert, ScD, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655.
Journal of the National Cancer Institute
Discussion
Table 1. Smoking and lung cancer in men: full distribution*
Never smokers
1-19 CPD
Current smokerst 20-29 CPD
30+CPD
88 853 1.00
99 250 3.84 (2.69-5.47)
223 259 8.35 (6.26-11.12)
402 357 10.92 (8.42-14.15)
No. of case patients No. of control patients Odds ratio (95% CI)
•Current and never smokers. tCPD = cigarettes per day. Chi-square test for linear trend = 409.53.
Table 2. Smoking and lung cancer in men: truncated distribution*
15-20 CPD No. of case patients No. of control patients Odds ratio (95% CI)
234 293 1.00
Current smokerst 21-30 CPD 31-40 CPD 129 153 1.04 (0.77-1.40)
174 150 1.45 (1.11-1.71)
41+CPD 123 83 1.86 (1.37-2.51)
•Taking the 55th to the 100th percentile of the full distribution. tCPD = cigarettes per day. Chi-square test for linear trend = 16.63.
to an odds ratio of 1.77 (95% CI = 1.262.50) in the truncated distribution (chisquare for trend = 9.54). Tables 3 and 4 show the results for women. For the full distribution (Table 3), a stronger incremental risk was found for women than for men. With the loss of the lowest 55% of the distribution, we found sparse data in the highest exposure category (41+ cigarettes smoked per day), resulting in a reversal of the pattern of increasing risk observed by
amount smoked in the middle two quartiles relative to the lowest exposure category (15-20 cigarettes smoked per day). The results for current women smokers showed a more severe reduction than we observed for men, from an odds ratio of 5.30 (95% CI = 3.69-7.62) across extreme quartiles of the full currentsmoker distribution (chi-square for trend = 59.63) to an odds ratio of 1.20 (95% CI = 0.68-2.13) in the truncated distribution (chi-square for trend = 1.13).
Table 3. Smoking and lung cancer in women: full distribution*
Never smokers
1-19 CPD
Current smokerst 20-29 CPD
30+CPD
97 868 1.00
85 155 4.91 (3.40-7.08)
166 115 12.92 (9.56-17.45)
220 100 19.69 (14.86-26.07)
No. of case patients No. of control patients Odds ratio (95% CI)
•Current and never smokers. tCPD = cigarettes per day. Chi-square test for linear trend = 501.89. Table 4. Smoking and lung cancer in women: truncated distribution*
15-20 CPD No. of case patients No. of control patients Odds ratio (95% CI)
174 138 1.00
Current smokerst 21-30 CPD 31-40 CPD 113 60 1.49 (1.06-2.11)
•Taking the 55th to the 100th percentile of the full distribution. tCPD = cigarettes per day. Chi-square test for linear trend = 13.37.
Vol. 83, No. 12, June 19, 1991
98 33 2.36 (1.65-3.37)
41+CPD 34 15 1.80 (1.06-3.04)
Dietary fat is the nutrient most strongly related to cancer risk in ecological data (12). The lack of effect observed in analytic studies may be due to the absence of low levels of fat exposure in populations from which study samples are drawn (3-17). Many laboratory experiments indicate that a strong effect of fat intake on cancer risk is shown only by comparison with animals eating fewer than 25% of their calories as fat (25-27). For all practical purposes, this low fat intake is outside the range of what is observed in human populations of the United States or other western countries. The portion of the smoking distribution we analyzed was equivalent to the fraction of the world distribution of fat represented by the distribution of dietary fat in the United States. This exercise dramatically demonstrated that the toss of a large portion of the lower part of the distribution of cigarette smoking results in a striking diminution of risk estimates for lung cancer. For both men and women, we observed the strongest incremental effect of tobacco at lower doses of cigarettes smoked per day. For example, there is nearly a fourfold increase in lung cancer risk between male current smokers of 1 19 cigarettes per day and subjects who have never smoked, whereas there is less than a threefold (ie, odds ratio = 2.56) risk among smokers of 20+ cigarettes per day compared with those smoking 1-19 cigarettes per day. Among women, there is an odds ratio of 4.91 in smokers of 1-19 cigarettes per day compared with those subjects who have never smoked but an odds ratio of only 3.27 in women smokers of 20+ cigarettes per day compared with those smoking 1-19 cigarettes per day. The quantitative differences observed between the sexes may be due to a more marked effect of cigarette smoking among women (25). The nonlinearity that we observed in dose-response is not uncommon in epidemiologic studies (29^0). It is apparent that the never smokers in our study provided the largest contrast in the data. That is, the odds ratio obtained in comparing never smokers to smokers in
BRIEF COMMUNICATION 873
the second quartile of the full distribution was larger than any obtained in comparing other adjacent quartiles. By removing that portion of the distribution at lowest risk of disease, we diluted our estimates of association by forcing the analysis into the high-risk realm, in which risk relationships are most difficult to observe (37). It has been suggested that estimates of the effect of dietary fat and cancer risk in humans are attenuated in much the same way, though to a greater extent (32). Given evidence that indicates fat-cancer effects are not as linear as are smokinglung cancer effects (25-27), the loss of the lower 55% of the fat distribution may pose more serious problems for estimation of dietary fat-cancer relationships. This work points out the need to identify study groups consuming diets that lie outside the range of typical North American and European fat intake if we wish to estimate the true potential effect of dietary fat on human cancer (32 J 3).
References tors and cancer incidence and mortality in different countries, with special references to dietary practices. Int J Cancer 15:617-631, 1975 (2) CARROLL KK, KHOR HT: Dietary fat in rela-
tion to tumorigenesis. Prog Biochem Pharmacol 10:308-353, 1975 (3) WILLETT WC, STAMPFER MJ, COLDFTZ GA,
ET AL: Dietary fat and the risk of breast cancer. N Engl J Med 316:22-28, 1986 K,
WILLETT W, TRICHOP.
OULOS D, ET AL: Risk of breast cancer among
12
AL: An epidemiologic study on the association between diet and breast cancer. JNCI 78:595-600,1987 Dietary habits and breast cancer incidence among Seventh-day Adventists. Cancer 64:582-590,1989 (7) BYERS T: Diet and cancer: Any progress in the interim? Cancer 62:1713-1724, 1988 KR, ET AL: Physical activity, diet, andriskof colon cancer in Utah. Am J Epidemiol 128:989-999,1988 POTTER
JD:
Diet
and
colonic cancer. Integration of the descriptive, analytic, and metabolic epidemiology. Natl Cancer Inst Monogr 69:223-228,1985
Diet in the epidemiology of carcinoma of the prostate gland. JNCI 70:687-692, 1983 (12) FLANDERS WD: Review: Prostate cancer epidemiology. Prostate 5:621-629, 1984 (13) SNOWDON DA, PHILLIPS RL, CHOI W: Diet,
obesity, and risk of fatal prostate cancer. Am J Epidemiol 120:244-250, 1984
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(29) SCHIFFLERS E, JAMART J, RENARD V: Tobac-
Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64:598— 604, 1989
co and occupation as risk factors in bladder cancer: A case-control study in southern Belgium. Int J Cancer 39:287-292, 1987 (30) AUGUSTINE A, HEBERT JR, KABAT GC, ET
AL: Bladder cancer in relation to cigarette smoking. Cancer Res 48:4405-4408, 1988
(16) HEBERT JR, WYNDER EL: Dietary fat and the
risk of breast cancer. N Engl J Med 317:165— 166,1987 (17) WYNDER EL, HEBERT JR: Homogeneity in
nutritional exposure: An impediment in cancer epidemiology. JNCI 79:605-607, 1987 (18) WiLLETT W: Nutritional Epidemiology. New York: Oxford Univ Press, 1990
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Effect of varying proportions of dietary fat on the development of /V-nitrosomethylureainduced rat mammary tumors. Anticancer Res 6:215-218, 1986 (26) BIRT DF: The influence of dietary fat on carcinogenesis: Lessons from experimental models. Nutr Rev 48:1-5, 1990 (27) WEISBURGER JH: Role of fat, fiber, nitrate, and food additives in carcinogenesis: A critical evaluation and recommendations. Nutr Cancer 8:47-62, 1986
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Smoking and adult leukemia: A case-control study. J Clin Epidemiol 41:907-914, 1988
A case-control study of relationships of diet and other traits to colorectal cancer in American blacks. Am J Epidemiol 109:132144,1978
sociation of dietary fat and lung cancer. J Nad Cancer Inst 79:631-637, 1987
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(24) KABAT GC, AUGUSTINE A, HEBERT JR:
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(19) WYNDER EL, HEBERT JR, KABAT GC: As-
1979-1981 average. Rome: FAO, 1981
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(31) ROTHMAN KJ, POOLE C: A strengthening
programme for weak associations. Int J Epidemiol 17:955-959, 1988 (32) HEBERT JR, MILLER DR: Methodologic con-
siderations for investigating the diet-cancer link. Am J Clin Nutr 47:1068-1077, 1988 (33) ZARIDZE DG, MUIR CS, MCMICHAEL AJ:
Diet and cancer: Value of different types of epidemiological studies. Nutr Cancer 7:155— 166,1985
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