Lower risk of smoking-related cancer in individuals with familial hypercholesterolemia compared with controls: a prospective matched cohort study

Abstract

According to guidelines, individuals with familial hypercholesterolemia (FH) shall receive lifestyle intervention and intensive lipid-lowering treatment from early in life to reduce the risk of coronary heart disease. Our aim was to study if treatment of FH also could affect risk of lifestyle-related cancer. We presented cumulative incidence of total cancer and lifestyle-related cancer sites in individuals with genetically verified FH (n = 5531) compared with age and sex matched controls (n = 108354). Individuals with FH had 20% lower risk of smoking-related cancer compared with the control population [HR 0.80 (95% CI, 0.65–0.98)], in particular men with FH at 40–69 years at age of diagnosis with HR 0.69 (95% CI, 0.49–0.97). The FH population and controls had similar rates of total cancer [HR 0.97 (95% CI, 0.86–1.09)], cancer related to poor diet [HR 0.82 (95% CI, 0.59–1.15)], cancer related to physical inactivity [HR 0.93 (95% CI, 0.73–1.18)], alcohol-related cancer [HR 0.98 (95% CI, 0.80–1.22)] and cancer related to obesity [HR 1.03 (95% CI, 0.89–1.21)]. In summary, we found reduced risk of smoking-related cancer in individuals with FH, most likely due to a lower prevalence of smoking. Implications of these findings can be increased motivation and thus compliance to treatment of hypercholesterolemia.

2.5-fold increased risk of recurrent acute myocardial infarction with familial hypercholesterolemia

“…This is a prospective matched cohort study comprising individuals with genetically verified FH and age and sex matched non-FH controls obtained from the general population. The FH population was obtained from the Unit for Cardiac and Cardiovascular Genetics (UCCG) database at Oslo University Hospital, where all individuals with FH are included after genetic diagnosis and after obtaining written informed consent [3,10]. In Norway, the majority of individuals with genetically verified FH are identified through cascade screening, meaning that the relatives of an index patient are tested for different FH mutations [3,10].…”

“…Of these, we were missing exact inclusion date and hence the date of genetically verified FH diagnosis in 744 individuals who were diagnosed prior to 1992. These individuals were assigned the inclusion date January 1, 1992, as previously described [10]. For each individual with FH, 20 controls living in Norway in the same time period were matched according to sex and age, yielding a non-FH control sample of 112,589 individuals.…”

“…For each individual with FH, 20 controls living in Norway in the same time period were matched according to sex and age, yielding a non-FH control sample of 112,589 individuals. This inclusion of a matched control sample was performed as an overall goal to study risk of several diseases including cancer [10]. In the present study, we excluded 764 individuals with FH and 16,338 controls who either had been hospitalized with AMI or were deceased before study start or who were <20 years of age before study end (December 31, 2017).…”

“…The Regional Committee of Medical and Health Research Ethics South-Eastern Norway approved the study (reference 2011/1343 REK Sør-Øst B). The study was granted exemption from the obligation to obtain informed consent, as previously described [10]. The study complies with the Declaration of Helsinki and was reported to the Norwegian Data Protection Official at Oslo University Hospital.…”

Obesity, Type 2 Diabetes, and Cancer Risk

“…Though no difference was found in total cancer mortality rate ( 99 ), a strong association was found with death rates from pancreatic cancer ( 100 ). In contrast, lower incidences of smoking-related cancers in individuals with FH have been observed, which may be attributed to decreased smoking as a lifestyle modification ( 101 ).…”