title: Sequence variation in proprotein convertase subtilisin/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence.
abstract: 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.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA. folsom@epi.umn.edu
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: James M
authors.initials: JM
authors.lastname: Peacock
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D044383:Black People; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011446:Prospective Studies; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People; D001741:Black or African American
chemical_list: D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases