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      Sequence variation in proprotein convertase subtilisin/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence.

      Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
      African Continental Ancestry Group, Cholesterol, LDL, blood, Cohort Studies, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Neoplasms, enzymology, epidemiology, genetics, Proprotein Convertases, Prospective Studies, Serine Endopeptidases, United States

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          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.

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