Amencan Journal of Epidemiology Copyright C 1991 by "Ore Johns Hopkins Urnversrty School of Hygiene and Pubic Health All rights reserved
Vol 134, No 9 Printed in U.S.A
A BRIEF ORIGINAL CONTRIBUTION
Cigarette Smoking and Risk of Adult Leukemia
Ross C. Brownson,1 Jian C. Chang,2 and James R. Davis3
A case-control study investigated the relation between cigarette smoking and histologic subtypes of adult leukemia in Missouri in 1984-1990. Among males, elevated risks associated with ever smoking were observed for acute nonlymphocytic leukemia (odds ratio (OR) = 1.5; 95% confidence interval (Cl) 1.1-2.0) and acute myelocytic leukemia (OR = 1.5; 95% Cl 1.1-2.1). Females also showed an increased risk of acute nonlymphocytic leukemia associated with ever smoking (OR = 1.4; 95% Cl 1.0-1.9), with an increasing trend in risk by level of smoking (p < 0.01). Attributable risk estimates of the proportion of acute nonlymphocytic leukemia caused by smoking were 33 percent in males and 29 percent in females. Elevations in risk were not apparent for chronic forms of leukemia. The findings support the hypothesis that some types of leukemia may be etiologically related to cigarette smoking. Am J Epidemiol 1991 ;134:938-41. leukemia, lymphocytic, chronic; leukemia, myelocytic, acute; leukemia, myeloid, chronic; leukemia, nonlymphocytic, acute; smoking
Although leukemia has not been commonly regarded as a smoking-related cancer, eight recent studies (1-8) have identified a positive association between cigarette smoking and leukemia. Elevations in risk of leukemia in these studies have ranged from 28 to 144 percent. Each of the eight analyses has shown evidence of a dose-response relation based on a measure of either duration or level of smoking. If this is a causal relation, smoking may account for more deaths
from adult leukemia than all other known causes combined (2, 9). Austin and Cole (10) have pointed out that some studies may have overlooked the smoking-leukemia association because of the lack of specific design to investigate the relation and failure to analyze by histologic subtype. These observations and limited positive findings have resulted in recommendations for additional studies on this potentially important association (3-5, 710). To investigate further the association between cigarette smoking and various forms of adult leukemia, we conducted a casecontrol study based on data from a statewide cancer registry.
Received fof publication November 26, 1990, and in final form May 2, 1991. Abbreviations. Q, confidence interval, OR, odds ratio. 1 Division of Chronic Disease Prevention and Health Promotion, Missouri Department of Health, Columbia, MO 2 Missouri Cancer Registry, Missoun Department of Health, Columbia, MO 3 Bureau of Smoking, Tobacco, and Cancer, Missoun Department of Health, Columbia, MO Reprint requests to Dr. Ross C. Brownson, Director, Division of Chronic Disease Prevention and Health Promotion, Missouri Department of Health, 201 Business Loop 70 West, Columbia, MO 65203. The authors thank the staff of the Missouri Cancer Registry for assistance with data collection and analysis.
MATERIALS AND METHODS
Subjects were identified through the Missouri Cancer Registry, which is maintained by the Missouri Department of Health. The Registry began collecting data on incident 938
Cigarette Smoking and Leukemia
cancer cases from public and private hospitals in 1972. Hospital reporting has been mandated by law since 1984. Reporting procedures have been discussed in more detail elsewhere (11).
939
smoked per day. Smoking history was unknown for 29 percent of cases and 27 percent of controls. An additional 2 percent each of cases and controls used other forms of tobacco such as cigars, pipes, and smokeless tobacco products.
Cases
Cases were white Missouri residents, aged 20 years and older, who were diagnosed with histologically confirmed leukemia (International Classification of Diseases for Oncology morphology codes 9800-9940) (12) between January 1984 and March 1990. Selection was limited to whites due to the small number of nonwhites. A total of 1,648 eligible cases were identified. Controls
Controls were white Missouri residents, aged 20 years and older, who were diagnosed with other types of cancer during the same time period. Those with cancers considered to be strongly related to smoking (i.e., cancers of the lip, oral cavity, esophagus, lung, and bladder (13)) and those with cancers at ill-defined or unknown sites were excluded from control group selection. Controls were frequency matched to cases by age group at an approximate three-to-one ratio and numbered 5,138. Cancers of the colon (17 percent of controls), breast (16 percent), and prostate (16 percent) predominated in the control series. Other control group sites that may be associated with smoking included cancers of the stomach (2 percent), pancreas (4 percent), and uterine cervix (4 percent). Those with endometrial cancer, which may be inversely related to smoking, comprised 3 percent of the control group.
Analysis
The measure of association between cigarette smoking and leukemia was the odds ratio. Age-adjusted maximum likelihood estimates of the odds ratio and 95 percent confidence intervals were calculated by the method of Gait (14). The age groups used for odds ratio adjustment were 0-64, 65-74, and 75 years and older. The linearity of trends in risk according to level of smoking was evaluated with Mantel's one-tailed test (15). RESULTS
Table 1 presents the distribution of male cases and controls according to smoking status and level. Elevated risks associated with ever smoking were observed for acute nonlymphocytic leukemia (odds ratio (OR) = 1.5; 95 percent confidence interval (CI) 1.12.0) and acute myelocytic leukemia (OR = 1.5; 95 percent CI 1.1 -2.1). No linear trends in risk with number of cigarettes per day, significant at the p = 0.05 level, were identified among males. Females also showed an increased risk of acute nonlymphocytic leukemia associated with ever smoking (OR = 1.4; 95 percent CI 1.0-1.9), with an increasing trend in risk by level of smoking (p < 0.01) (table 2). A nonsignificantly elevated risk (OR = 1.3) of acute myelocytic leukemia was observed for ever smoking.
Smoking information
Data on cigarette smoking are routinely abstracted from the medical record at the time of diagnosis by hospital registrars using a standardized protocol. These data are subsequently reported to the Missouri Cancer Registry and coded by the Registry staff according to smoking status (i.e., never, former, or current use) and, among current smokers, according to the number of packs
DISCUSSION
This study supports other recent studies (1-8) that suggest a positive association between cigarette smoking and some forms of leukemia. It should be noted, however, that two studies (16, 17) have shown little evidence of a relation between smoking and leukemia. It is somewhat difficult to compare di-
940
Brownson et al.
TABLE 1. Age-adjusted odds ratios (OR) and 95% confidence Intervals (Cl) for leukemia according to smoking status am1 level, males, Missouri, 1984-1990 Ever smoked
Level of smoking (cigarettes/day)*
Group
Vol 134, No 9 Printed in U.S.A
A BRIEF ORIGINAL CONTRIBUTION
Cigarette Smoking and Risk of Adult Leukemia
Ross C. Brownson,1 Jian C. Chang,2 and James R. Davis3
A case-control study investigated the relation between cigarette smoking and histologic subtypes of adult leukemia in Missouri in 1984-1990. Among males, elevated risks associated with ever smoking were observed for acute nonlymphocytic leukemia (odds ratio (OR) = 1.5; 95% confidence interval (Cl) 1.1-2.0) and acute myelocytic leukemia (OR = 1.5; 95% Cl 1.1-2.1). Females also showed an increased risk of acute nonlymphocytic leukemia associated with ever smoking (OR = 1.4; 95% Cl 1.0-1.9), with an increasing trend in risk by level of smoking (p < 0.01). Attributable risk estimates of the proportion of acute nonlymphocytic leukemia caused by smoking were 33 percent in males and 29 percent in females. Elevations in risk were not apparent for chronic forms of leukemia. The findings support the hypothesis that some types of leukemia may be etiologically related to cigarette smoking. Am J Epidemiol 1991 ;134:938-41. leukemia, lymphocytic, chronic; leukemia, myelocytic, acute; leukemia, myeloid, chronic; leukemia, nonlymphocytic, acute; smoking
Although leukemia has not been commonly regarded as a smoking-related cancer, eight recent studies (1-8) have identified a positive association between cigarette smoking and leukemia. Elevations in risk of leukemia in these studies have ranged from 28 to 144 percent. Each of the eight analyses has shown evidence of a dose-response relation based on a measure of either duration or level of smoking. If this is a causal relation, smoking may account for more deaths
from adult leukemia than all other known causes combined (2, 9). Austin and Cole (10) have pointed out that some studies may have overlooked the smoking-leukemia association because of the lack of specific design to investigate the relation and failure to analyze by histologic subtype. These observations and limited positive findings have resulted in recommendations for additional studies on this potentially important association (3-5, 710). To investigate further the association between cigarette smoking and various forms of adult leukemia, we conducted a casecontrol study based on data from a statewide cancer registry.
Received fof publication November 26, 1990, and in final form May 2, 1991. Abbreviations. Q, confidence interval, OR, odds ratio. 1 Division of Chronic Disease Prevention and Health Promotion, Missouri Department of Health, Columbia, MO 2 Missouri Cancer Registry, Missoun Department of Health, Columbia, MO 3 Bureau of Smoking, Tobacco, and Cancer, Missoun Department of Health, Columbia, MO Reprint requests to Dr. Ross C. Brownson, Director, Division of Chronic Disease Prevention and Health Promotion, Missouri Department of Health, 201 Business Loop 70 West, Columbia, MO 65203. The authors thank the staff of the Missouri Cancer Registry for assistance with data collection and analysis.
MATERIALS AND METHODS
Subjects were identified through the Missouri Cancer Registry, which is maintained by the Missouri Department of Health. The Registry began collecting data on incident 938
Cigarette Smoking and Leukemia
cancer cases from public and private hospitals in 1972. Hospital reporting has been mandated by law since 1984. Reporting procedures have been discussed in more detail elsewhere (11).
939
smoked per day. Smoking history was unknown for 29 percent of cases and 27 percent of controls. An additional 2 percent each of cases and controls used other forms of tobacco such as cigars, pipes, and smokeless tobacco products.
Cases
Cases were white Missouri residents, aged 20 years and older, who were diagnosed with histologically confirmed leukemia (International Classification of Diseases for Oncology morphology codes 9800-9940) (12) between January 1984 and March 1990. Selection was limited to whites due to the small number of nonwhites. A total of 1,648 eligible cases were identified. Controls
Controls were white Missouri residents, aged 20 years and older, who were diagnosed with other types of cancer during the same time period. Those with cancers considered to be strongly related to smoking (i.e., cancers of the lip, oral cavity, esophagus, lung, and bladder (13)) and those with cancers at ill-defined or unknown sites were excluded from control group selection. Controls were frequency matched to cases by age group at an approximate three-to-one ratio and numbered 5,138. Cancers of the colon (17 percent of controls), breast (16 percent), and prostate (16 percent) predominated in the control series. Other control group sites that may be associated with smoking included cancers of the stomach (2 percent), pancreas (4 percent), and uterine cervix (4 percent). Those with endometrial cancer, which may be inversely related to smoking, comprised 3 percent of the control group.
Analysis
The measure of association between cigarette smoking and leukemia was the odds ratio. Age-adjusted maximum likelihood estimates of the odds ratio and 95 percent confidence intervals were calculated by the method of Gait (14). The age groups used for odds ratio adjustment were 0-64, 65-74, and 75 years and older. The linearity of trends in risk according to level of smoking was evaluated with Mantel's one-tailed test (15). RESULTS
Table 1 presents the distribution of male cases and controls according to smoking status and level. Elevated risks associated with ever smoking were observed for acute nonlymphocytic leukemia (odds ratio (OR) = 1.5; 95 percent confidence interval (CI) 1.12.0) and acute myelocytic leukemia (OR = 1.5; 95 percent CI 1.1 -2.1). No linear trends in risk with number of cigarettes per day, significant at the p = 0.05 level, were identified among males. Females also showed an increased risk of acute nonlymphocytic leukemia associated with ever smoking (OR = 1.4; 95 percent CI 1.0-1.9), with an increasing trend in risk by level of smoking (p < 0.01) (table 2). A nonsignificantly elevated risk (OR = 1.3) of acute myelocytic leukemia was observed for ever smoking.
Smoking information
Data on cigarette smoking are routinely abstracted from the medical record at the time of diagnosis by hospital registrars using a standardized protocol. These data are subsequently reported to the Missouri Cancer Registry and coded by the Registry staff according to smoking status (i.e., never, former, or current use) and, among current smokers, according to the number of packs
DISCUSSION
This study supports other recent studies (1-8) that suggest a positive association between cigarette smoking and some forms of leukemia. It should be noted, however, that two studies (16, 17) have shown little evidence of a relation between smoking and leukemia. It is somewhat difficult to compare di-
940
Brownson et al.
TABLE 1. Age-adjusted odds ratios (OR) and 95% confidence Intervals (Cl) for leukemia according to smoking status am1 level, males, Missouri, 1984-1990 Ever smoked
Level of smoking (cigarettes/day)*
Group
