title: Adjustment for smoking does not alter the FOXO3A association with longevity.
abstract: Human longevity is a multifactorial phenotype influenced by both genetic and environmental factors. Despite its heritability of 25-32 %, the genetic background of longevity is as yet largely unexplained. Apart from APOE status, variation in the FOXO3A gene is the only confirmed genetic contributor to survival into old age. On the other hand, FOXO3A activity is known to be downregulated in various cancers, and the gene was recently identified as a novel deletion hotspot in human lung adenocarcinoma. In view of the strong association between smoking and lung cancer, we set out to explore whether smoking modifies the known association between FOXO3A variation and longevity. To this end, we conducted a case-control study in two different populations, drawing upon extensive collections of old-aged individuals and younger controls available to us (1,613 German centenarians/nonagenarians and 1,104 controls; 1,088 Danish nonagenarians and 736 controls). In the German sample, 21 single nucleotide polymorphisms (SNPs) from the FOXO3A gene region were genotyped, whereas 15 FOXO3A SNPs were analyzed in the Danish sample. Eight SNPs were typed in both populations. Logistic regression analysis revealed that adjustment for smoking does not systematically alter the association between FOXO3A variation and longevity in neither population. Our analysis therefore suggests that the said association is not largely due to the confounding effects of lung cancer.
authors.affiliation: Institute of Medical Informatics and Statistics, Christian-Albrechts University, Brunswiker Straße 10, 24105, Kiel, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Däumer
authors.forename: Friederike
authors.initials: F
authors.lastname: Flachsbart
authors.forename: Amke
authors.initials: A
authors.lastname: Caliebe
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000235:genetics*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008136:Longevity / Q000235:genetics*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D004247:DNA