Counterpoint
The Myeloperoxidase −463G→A Polymorphism Does Not Decrease Lung Cancer Susceptibility in Caucasians1
- Li-Lian Xu2,
- Geoffrey Liu2,
- David P. Miller,
- Wei Zhou,
- Thomas J. Lynch,
- John C. Wain,
- Li Su and
- David C. Christiani3
- Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115 [L-L. X., G. L., D. P. M., W. Z., L. S., D. C. C.], and Thoracic Surgery Unit, Department of Surgery [J. C. W.], Pulmonary and Critical Unit Medicine [D. C. C.] and Cancer Center, Division of Hematology-Oncology [G. L., T. J. L.], the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
Abstract
The myeloperoxidase (MPO) G-to-A substitution polymorphism in the promoter region of the MPO gene has been associated with a 40–70% reduction in lung cancer risk in several studies, although a recent nested case-control study disputes these findings. MPO is involved in the activation of a number of procarcinogens, including benzo(a)pyrene. The variant A allele has been shown to reduce MPO mRNA expression, thus potentially decreasing carcinogen activation. To confirm results from smaller studies, we evaluated this MPO polymorphism in 988 incident Caucasian lung cancer cases and 1128 controls. Logistic regression evaluated the association between MPO genotype and lung cancer risk, adjusting for age, gender, smoking status, time since quitting smoking, and pack-years of smoking. In the controls, the A allele frequency was 21%, and genotype distribution was in the Hardy-Weinberg equilibrium. Compared with the wild-type G/G genotype, the adjusted odds ratios for the A/A and A/G genotypes were 1.15 (95% confidence interval 0.7–1.9, P > 0.2) and 1.03 (95% confidence interval 0.8–1.3, P > 0.20), respectively. A similar lack of association was seen in analyses stratified by smoking status, median age, a number of smoking variables, disease stage, tumor grade, and histological subtype. These findings are in contrast with earlier studies suggesting a protective effect of carrying the variant A allele.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by NIH Grants CA74386, ES/CA06409, and ES00002. Dr. Xu was supported by training grant ES T3207069, and Dr. Liu was supported by a Doris Duke Clinical Scientist Development Award and a Charles A. King research fellowship.
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↵2 L-L. X. and G. L. contributed equally to this work.
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↵3 To whom requests for reprints should be addressed, at the Occupational Health Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. Phone: (617) 432-3323; Fax: (617) 432-3441; E-mail: dchris{at}hohp.harvard.edu
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↵4 The abbreviations used are: MPO, myeloperoxidase; SR-PY, square root pack-years; OR, odds ratio; CI, confidence interval.
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- Accepted September 20, 1902.
- Received June 22, 1901.
- Revision received September 12, 1902.
