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CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

¹ Department of Medicine and ² Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, California; ³ School of Public Health, University of California, Berkeley, California; ⁴ Department of Laboratory Medicine and Pathology, Brown University, Providence, Rhode Island; ⁵ Division of Research, Kaiser Permanente, Oakland, California; and ⁶ Rowe Program in Human Genetics, Departments of Biological Chemistry and Medicine, University of California, Davis, California

Requests for reprints: Melinda C. Aldrich, Department of Medicine, University of California, 1550 4th Street, MC2911, San Francisco, CA 94158. Phone: 415-514-4838; Fax: 415-514-4365; E-mail: melinda.aldrich{at}ucsf.edu.

Key Words: lung cancer • haplotype • CYP1A1/2 • population stratification • admixed

Prior studies of lung cancer and CYP1A1/2 in African-American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of CYP1A1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998–2003). African-Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28–3.19 and OR, 0.55; 95% CI, 0.36–0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos. [Cancer Res 2009;69(6):2340–8]