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Sequence Variation in Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease Gene, Low LDL Cholesterol, and Cancer Incidence

¹ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; ² The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas; and ³ Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas

Requests for reprints: Aaron R. Folsom, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454. Phone: 612-626-8862; Fax: 612-624-0315. E-mail: folsom{at}epi.umn.edu

Some prospective epidemiologic studies have suggested that a low plasma cholesterol level may be associated with increased risk of cancer. Certain sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) are associated with lifelong low total and LDL cholesterol. We therefore analyzed the association of PCSK9 variation with incidence of cancer between 1987 and 2000 in a prospective study (n = 13,250). The frequency of the PCSK9 variants studied was 2.4% in blacks and 3.2% in whites. Neither was associated with increased cancer incidence: age- and sex-adjusted hazard ratios were 0.66 [95% confidence interval (95% CI), 0.31-1.39] in blacks and 0.77 (95% CI, 0.54-1.09) in whites. Low baseline total or LDL cholesterol levels in 1987 to 1989 were also not statistically significantly associated with incident cancer: multivariable-adjusted hazard ratios for the lowest compared with the highest quartiles of LDL cholesterol were 1.05 (95% CI, 0.78-1.40) in blacks and 1.16 (95% CI, 0.99-1.36) in whites. These data suggest that a lifelong low cholesterol concentration, as reflected by these PCSK9 variants, does not increase risk of cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2455–8)