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

TitleSequence variation in proprotein convertase subtilisin/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence.
Publication TypeJournal Article
Year of Publication2007
AuthorsFolsom AR, Peacock JM, Boerwinkle E
JournalCancer Epidemiol Biomarkers Prev
Volume16
Issue11
Pagination2455-8
Date Published2007 Nov
ISSN1055-9965
KeywordsAfrican Continental Ancestry Group, Cholesterol, LDL, Cohort Studies, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Neoplasms, Proprotein Convertase 9, Proprotein Convertases, Prospective Studies, Serine Endopeptidases, United States
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.

DOI10.1158/1055-9965.EPI-07-0502
Alternate JournalCancer Epidemiol Biomarkers Prev
PubMed ID18006936
Grant ListN01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
R03-CA65473 / CA / NCI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States