RE: "DOSE-SPECIFIC META-ANALYSIS AND SENSITIVITY ANALYSIS OF THE RELATION BETWEEN ALCOHOL CONSUMPTION AND LUNG CANCER RISK"

Elisa V. Bandera1 and John D. Potter2

1 The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903.
2 Fred Hutchinson Cancer Research Center, Seattle, WA 98109.

We read with great interest the meta-analysis by Korte et al. (1), which addressed the controversial relation between alcohol consumption and lung cancer. Although we agree with their general conclusions, a few issues should be taken into account when interpreting the results of their meta-analysis and the overall evidence for an association.

First, although the effect of the different alcoholic beverages on lung cancer risk is not completely understood, studies have generally reported a stronger positive association for beer (2, 3) than for other alcoholic beverages, with some indication that wine—at moderate consumption levels—may decrease risk (3). Korte et al. (1), ignoring these findings, limited their analyses to total alcohol consumption. Perhaps their results would have been different if they had evaluated the effect of the different alcoholic beverages. Second, when studies presented results about recent and lifetime consumption, Korte et al. chose results "based on consumption frequency over as long a time span as possible" (1, p. 497). They offered no justification for this assumption. The latency period between exposure to alcohol and lung cancer development is unknown. However, there is some indication that alcohol and beer may act during the later stages of carcinogenesis (2, 4, 5) and, therefore, recent exposure may be the relevant exposure period.

Korte et al. (1) misclassified the Iowa Women’s Health Study (4), listing it in table 1 and including it in their analysis as a case-control study when it should have been listed as a cohort study. In addition, when they raised the issue of residual confounding by cigarette smoking, they cited as an example the Iowa Women’s Health Study (4), specifically as showing "an excess of extremely heavy smokers among the cases" (1, p. 504). In fact, Korte et al. attributed their findings of increased lung cancer risk among heavy drinkers to residual confounding. It is true that the proportion of heavy smokers was higher among cases than controls in the Iowa Women’s Health Study (4). However, mean pack-years was similar for cases and controls in each category of pack-years, except for heavy smokers (>50 pack-years). In this group, mean pack-years of cigarette smoking among cases was only slightly higher when compared with controls (77 vs. 70, p = 0.16). Furthermore, this subanalysis was undertaken specifically to explore whether residual confounding by tobacco explained the association found with beer consumption (4); it showed quite specifically that it did not.

The stronger association between total alcohol consumption and lung cancer reported by Korte et al. (1) for hospital-based case-control studies compared with population-based case-control studies could be due to geographic variation. For example, as their table shows, the strongest evidence comes from two hospital-based studies by De Stefani et al. (6) and Dosemeci et al. (7). These two studies were conducted in Uruguay and Turkey, respectively, and participants reported much higher levels of alcohol intake than in other studies. All other population-based case-control studies that adjusted for cigarette smoking listed in table 1 were conducted in the United States, where alcohol consumption tends to be lower and less socially accepted, therefore increasing the probability of underreporting. We again emphasize that results shown in this meta-analysis are for total alcohol only, and examining results for beer or liquor consumption may have provided a different picture. For example, the population-based case-control study by Carpenter et al. (8) listed in table 1 as finding no association for total alcohol (odds ratio = 0.68, 95 percent confidence interval: 0.33, 1.41) in fact found an elevated risk for those drinking one or more drinks of liquor per day (odds ratio = 1.9, 95 percent confidence interval: 1.0, 3.4). Furthermore, we found a relation between beer consumption and lung cancer in the Western New York Diet Study (9) and the Iowa Women’s Health Study (4), two population-based studies.

In summary, the meta-analysis of the relation between alcohol consumption and lung cancer by Korte et al. (1) raised again the important issue of residual confounding by cigarette smoking. However, when the evidence is evaluated, heavier weight should be given to studies that carefully assessed smoking and alcohol and controlled for cigarette smoking and other factors. Furthermore, we need to look at the effect of alcoholic beverages separately. If beer increases risk and wine decreases risk, as some studies have suggested, evaluating only total alcohol will mask associations. Residual confounding by cigarette smoking remains a challenge to studies examining the role of alcohol in lung cancer. However, the association observed among nonsmokers in some studies (1, 3) is intriguing, particularly considering their typically lower level of alcohol consumption. Although Korte et al. made efforts to conduct a comprehensive assessment of the epidemiologic evidence of an association between alcohol and lung cancer, their approach needs both greater specificity in relation to exposure and somewhat more careful assessment of the studies being meta-analyzed.

Editor’s note: In accordance with Journal policy, Korte et al. were asked whether they wanted to respond to this letter, but they chose not to do so.

REFERENCES

  1. Korte JE, Brennan P, Henley SJ, et al. Dose-specific meta-analysis and sensitivity analysis of the relation between alcohol consumption and lung cancer risk. Am J Epidemiol 2002;155:496–506.[Abstract/Free Full Text]
  2. Potter JD, McMichael AJ, Hartshorne JM. Alcohol and beer consumption in relation to cancers of bowel and lung: an extended correlation analysis. J Chronic Dis 1982;35:833–42.[CrossRef][ISI][Medline]
  3. Bandera EV, Freudenheim JL, Vena JE. Alcohol consumption and lung cancer: a review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev 2001;10:813–21.[Abstract/Free Full Text]
  4. Potter JD, Sellers TA, Folsom AR, et al. Alcohol, beer, and lung cancer in postmenopausal women. The Iowa Women’s Health Study. Ann Epidemiol 1992;2:587–95.[Medline]
  5. Nachiappan V, Mufti SI, Chakravarti A, et al. Lipid peroxidation and ethanol-related tumor promotion in Fischer-344 rats treated with tobacco-specific nitrosamines. Alcohol Alcohol 1994;9:565–74.
  6. De Stefani E, Correa P, Fierro L, et al. The effect of alcohol on the risk of lung cancer in Uruguay. Cancer Epidemiol Biomarkers Prev 1993;2:21–6.[Abstract]
  7. Dosemeci M, Gokmen I, Unsal M, et al. Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey. Cancer Causes Control 1997;8:729–37.[CrossRef][ISI][Medline]
  8. Carpenter CL, Morgenstern H, London SJ. Alcoholic beverage consumption and lung cancer risk among residents of Los Angeles County. J Nutr 1998;128:694–700.[Abstract/Free Full Text]
  9. Bandera EV, Freudenheim JL, Graham S, et al. Alcohol consumption and lung cancer in white males. Cancer Causes Control 1992;3:85–93.