Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Abstract

Purpose Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity. Methods The study-population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90+. The offspring of the long-lived siblings were followed 1968–2009. Using high quality registry data, observed numbers of cancers were compared to expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population. Results During the 41 year follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (SIRs) (95% confidence interval) for offspring of long-lived individuals were 0.78 (0. 70, 0.86) for overall cancer; 0.66 (0.56, 0.77) for tobacco-related cancer; 0.34 (0.22, 0.51) for lung cancer; 0.88 (0.71, 1.10) for breast cancer; 0.91 (0.62, 1.34) for colon cancer. Conclusions The low incidence of tobacco-related cancers in long-lived families compared to non-tobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark.

Mechanisms underlying familial aggregation of exceptional health and survival: A three‐generation cohort study

“…This minimizes loss to follow‐up and healthy participant bias at the expense of no available survey data on behavior. Using the Danish Cancer Registry, we have demonstrated low occurrence of cancers in the offspring of long‐lived siblings (Pedersen et al, 2015). We confirmed these findings using the Danish Patient Registry, and we extended the analyses to the grandchildren who, despite being followed only up to age 49, also showed lower cancer rates compared to controls, most pronounced for tobacco‐related cancers, although only borderline statistically significant.…”

“…The lower rates of tobacco‐related cancers in offspring and grandchildren could be due to both lower smoking frequency and/or higher biological resilience to the carcinogenic effects of tobacco in individuals with a familial history of longevity. Smoking habits in offspring were available for the subset of families in our study who also participated in the Long Life Family Study , and Pedersen et al (2015) showed that the prevalence of smokers in the offspring was 24% lower than that predicted from age‐ and sex‐specific smoking prevalence in the Danish population (Den Nationale & Sundhedsprofil, 2010).…”

“…In the supplement method, we provide more details. The LEFs included 3,972 siblings from 659 long-lived sibships (including the 76 Danish families in the Long Life Family Study (Ash et al, 2015;Barral et al, 2012Barral et al, , 2017Cosentino et al, 2013;Newman et al, 2011), their 5379 offspring, and their 10,398 grandchildren ( Figures 1 and 2, Table S1A,B) (Pedersen et al, 2015;Sebastiani et al, 2009).…”

“…The control groups comprised of the "corresponding" grandparents to the spouses to offspring of the long-lived siblings (Generation 0 in Figure 2). Only Generation 0 controls who had two children born in the same parish in Denmark before 1 April 1918 were included as this was the study base from which the LEF families were identified (Pedersen et al, 2015). Occupation distribution was grouped into four main groups (Statistics Denmark, 1920).…”

Healthy ageing, the genome and the environment

“…For example, in a 2015 population-based study that included the offspring of long-lived siblings (surviving to at least 90 years of age) the offspring had one third of the expected lung cancer incidence 8 . As the incidence of lung cancer is strongly correlated with lifestyle, these findings suggest that a healthy lifestyle might be a main driver for the familial clustering of exceptional good health.…”