Long-term cancer risk in heterozygous familial hypercholesterolemia relatives: a 25-year cohort study.
Cancer
Epidemiology
Genetics
Heterozygous familial hypercholesterolemia
Journal
Lipids in health and disease
ISSN: 1476-511X
Titre abrégé: Lipids Health Dis
Pays: England
ID NLM: 101147696
Informations de publication
Date de publication:
02 Jul 2022
02 Jul 2022
Historique:
received:
06
04
2022
accepted:
17
06
2022
entrez:
2
7
2022
pubmed:
3
7
2022
medline:
7
7
2022
Statut:
epublish
Résumé
Heterozygous familial hypercholesterolemia (HeFH) due to low-density lipoprotein receptor (LDLR) mutations predisposes patients to highly elevated levels of cholesterol, and patients are at increased risk of adverse cardiovascular events and other morbidities. Whether the LDLR mutation and high cholesterol levels affect the risk of cancer remains unknown. The purpose of the present study was to assess the long-term cancer risk in HeFH relatives. Study participants were identified by cascade screening during 1992-1994. A comparison cohort was matched 10:1 to the relatives from the Danish general population based on birth year, gender and address. All participants were followed until a cancer diagnosis, migration, death, or end of follow-up as of December 31, 2019. The primary endpoint was any incident cancer diagnosis. In total, we included 221 relatives with a median age of 37 years (interquartile range: 27-53 years). A total of 117 (53%) of the relatives carried a LDLR gene mutation. The crude hazard ratio of our primary endpoint did not reveal any differences in cancer incidence in mutation-carrying relatives compared with the general population cohort (1.18; 95% CI, 0.81-1.71). Nonmutation-carrying relatives however had a lower cancer incidence than the general population (0.45: 95% CI, 0.26-0.80). Thus, the risk among mutation-carrying HeFH relatives compared with nonmutation-carrying HeFH relatives was increased (HR: 2.39; 95% CI, 1.24-4.61). In Denmark, LDLR mutation-carrying HeFH relatives did not have a different cancer risk than the general population. In contrast, nonmutation-carrying relatives had a lower risk of cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Heterozygous familial hypercholesterolemia (HeFH) due to low-density lipoprotein receptor (LDLR) mutations predisposes patients to highly elevated levels of cholesterol, and patients are at increased risk of adverse cardiovascular events and other morbidities. Whether the LDLR mutation and high cholesterol levels affect the risk of cancer remains unknown. The purpose of the present study was to assess the long-term cancer risk in HeFH relatives.
METHODS
METHODS
Study participants were identified by cascade screening during 1992-1994. A comparison cohort was matched 10:1 to the relatives from the Danish general population based on birth year, gender and address. All participants were followed until a cancer diagnosis, migration, death, or end of follow-up as of December 31, 2019. The primary endpoint was any incident cancer diagnosis.
RESULTS
RESULTS
In total, we included 221 relatives with a median age of 37 years (interquartile range: 27-53 years). A total of 117 (53%) of the relatives carried a LDLR gene mutation. The crude hazard ratio of our primary endpoint did not reveal any differences in cancer incidence in mutation-carrying relatives compared with the general population cohort (1.18; 95% CI, 0.81-1.71). Nonmutation-carrying relatives however had a lower cancer incidence than the general population (0.45: 95% CI, 0.26-0.80). Thus, the risk among mutation-carrying HeFH relatives compared with nonmutation-carrying HeFH relatives was increased (HR: 2.39; 95% CI, 1.24-4.61).
CONCLUSION
CONCLUSIONS
In Denmark, LDLR mutation-carrying HeFH relatives did not have a different cancer risk than the general population. In contrast, nonmutation-carrying relatives had a lower risk of cancer.
Identifiants
pubmed: 35780163
doi: 10.1186/s12944-022-01666-2
pii: 10.1186/s12944-022-01666-2
pmc: PMC9250710
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Informations de copyright
© 2022. The Author(s).
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