Landmarkโ Study Reveals โGenetic Impact โขof Lifestyle & Health on Oral Cancer Mutation Rates
LONDON โฃ- A new study โpublishedโค inโ Nature has identified nine keyโ factorsโข – including age, sex, smoking history,โ alcohol โขconsumption,โฃ type โ2 diabetes, body mass index, tooth loss,โ physical activity, โand prior cancerโฃ history – that considerably influence somaticโ mutation burden in oral tissues at a population scale. Researchersโ analyzed data from a largeโ cohort, employing mixed-effects models to accountโค for familial relationships, and โfound these variables collectively shape the landscape โฃof genetic changes occurring in the mouth.
Theโ research team utilized multiple regressionโ models, โขstructured asโค lmer(SNVburden ~ age + sex + packyears + drinkyears + T2D + BMI + missingteeth + IPAQ + cancer + (1| familyID), REML=F), to assess the relationship between these โpredictorsโค and the burden of single nucleotide variants (SNVs). โฃ Data from โค12 samples showing potentialโ HPV evidence andโค 6 โฃwith a history of chemotherapy wereโ excluded due to potential โconfoundingโ effects, despite their relevance, owing to โlimited sample sizes.
Rigorous โฃstatisticalโข analysis, โคincluding Benjamini-Hochbergโ correctionโค for multipleโ testing across 126 โขtests (14 predictors x 9 outcome variables) โusing likelihood-ratio tests via โฃthe โค’drop1′ function in R, was โคemployed to determine the importance ofโ each covariate. โ
Further โanalyses, detailed in Supplementary Noteโ 7, explored โextended โฃmedication data, interactions between smokingโ and alcohol, and measures of selection. GWAS analyses and heritability tests are described in Supplementary Note 8. โ The R code used for all analyses isโ available in theโฃ Supplementary Code. Only samples withโค mean duplex coverage โฅ200x and complete metadata wereโฃ included.
This study providesโข critical insights into โthe interplay between environmental andโ genetic factors in oral cancer progress and offers a foundation for future research into personalized preventionโ strategies.