Landmark Study Reveals Genetic Impact of Lifestyle & Health on Oral Cancer Mutation Rates
LONDON - A new study published in Nature has identified nine key factors – including age, sex, smoking history, alcohol consumption, type 2 diabetes, body mass index, tooth loss, physical activity, and prior cancer history – that considerably influence somatic mutation burden in oral tissues at a population scale. Researchers analyzed data from a large cohort, employing mixed-effects models to account for familial relationships, and found these variables collectively shape the landscape of genetic changes occurring in the mouth.
The research team utilized multiple regression models, structured as lmer(SNVburden ~ age + sex + packyears + drinkyears + T2D + BMI + missingteeth + IPAQ + cancer + (1| familyID), REML=F), to assess the relationship between these predictors and the burden of single nucleotide variants (SNVs). Data from 12 samples showing potential HPV evidence and 6 with a history of chemotherapy were excluded due to potential confounding effects, despite their relevance, owing to limited sample sizes.
Rigorous statistical analysis, including Benjamini-Hochberg correction for multiple testing across 126 tests (14 predictors x 9 outcome variables) using likelihood-ratio tests via the ’drop1′ function in R, was employed to determine the importance of each covariate.
Further analyses, detailed in Supplementary Note 7, explored extended medication data, interactions between smoking and alcohol, and measures of selection. GWAS analyses and heritability tests are described in Supplementary Note 8. The R code used for all analyses is available in the Supplementary Code. Only samples with mean duplex coverage ≥200x and complete metadata were included.
This study provides critical insights into the interplay between environmental and genetic factors in oral cancer progress and offers a foundation for future research into personalized prevention strategies.
