Common mitochondrial haplogroups and cutaneous squamous cell carcinoma risk
Menée aux Etats-Unis à partir de données portant sur 7 701 patients atteints d'un carcinome épidermoïde cutané et sur 60 167 témoins, cette étude de cohorte rétrospective évalue l'association entre des haplogroupes de l'ADN mitochondrial et le risque de développer la maladie, en fonction du sexe de l'individu
Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in America, and its incidence is substantially higher in men than women, but the reasons for the difference are unknown. We explored whether common mitochondrial DNA (mtDNA) haplogroups, which have been associated with cancer risk, and in particular squamous cell carcinoma risk arising in other organs, could explain this biological sex difference in cSCC susceptibility. Methods: We performed a retrospective cohort study using data from the Genetic Epidemiology Research in Adult Health and Aging cohort comprised of 67,868 non-Hispanic white subjects (7,701 cSCC cases and 60,167 controls). Genotype information on > 665,000 single nucleotide polymorphisms (SNPs) was generated using Affymetrix Axiom arrays designed to maximize genome-wide coverage, and 102 high quality mtDNA SNPs were used to determine mtDNA haplogroups. Associations between each mtDNA haplogroup and cSCC risk were evaluated by logistic regression analysis adjusting for age, sex, and population stratification using ancestry principal components. Results: cSCC was more common in men (15.4% vs. 8.4% for women). Nine common mtDNA haplogroups (frequency ≥1%) were identified in addition to the most common haplogroup, H, used as the reference group. No association with cSCC risk was detected for any of the mtDNA haplogroups or overall or sex-stratified analyses. Conclusion: Common mitochondrial variation is not associated with cSCC risk. Impact: This well-powered study refutes the hypothesis that common mitochondrial hapolgroups play a role in the differential sex predilection of cSCCs.