Anil Chaturvedi

PhD

NCI

investigator

PLCO (Learn more about this study)

2017-0034

Jun 29, 2017

Somatic mutations in oral rinses and prospective risk of head and neck cancers

Head and neck cancers are the sixth most common cancers worldwide. Despite easy access of these anatomic sites for visual inspection and specimen collection, there are currently no modalities for screening, secondary prevention, and early detection of head and neck cancers. This situation partly reflects the current lack of risk stratification tools and predictive biomarkers for the identification of high-risk individuals.

Recent next-generation sequencing studies of head and neck cancer tumors have identified driver somatic mutations in several key genes/pathways, such as TP53, PIK3CA, CDKN2A, FBXW7, HRAS, NRAS, and FAT-1. Furthermore, a recent study by our laboratory collaborators (Wang et al., Sci Transl Med, 2015) showed that these somatic mutations could be detected at cancer diagnosis in saliva/oral rinse samples in a high proportion of patients with head and neck cancers (100% of oral cavity cancers, 70% of larynx cancers, 67% of hypopharynx cancers, and 47% of oropharynx cancers). These results indicate that the detection of driver somatic mutations in less-invasively collected samples, such as oral rinses, saliva, and buccal swabs, could provide a promising modality for the identification of individuals at high-risk of head and neck cancer. However, whether these mutations can be detected in oral rinses/saliva/buccal swabs prior to clinical diagnosis of cancer is not known, and prospective studies are currently lacking in the literature.

We propose to conduct a case-cohort study of 229 head and neck cancers and 458 controls within three population-based US cohorts—the control arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the NIH-AARP Diet and Health Study, and the Agricultural Health Study to investigate whether driver somatic mutations could be identified in oral rinses/buccal swabs prior to the detection of head and neck cancers. Cases will include individuals with incident head and neck cancers, including cancers of the oral cavity, oropharynx, hypopharynx, and larynx. Controls will represent a random sample of each cohort, stratified by 5-year age group, gender, and smoking (ever, former, current), and will be matched at a 2:1 ratio to cases. We propose to utilize DNA from oral rinses collected within each cohort to evaluate the presence of somatic mutations in 29 key driver genes that have been found to be significantly mutated in head and neck cancers within The Cancer Genome Atlas (TCGA) project. Analyses will be conducted overall as well as stratified by anatomic sites (oral cavity, pharynx, and larynx). Analyses will be conducted for each of the 29 individual genes, the number of genes per patient with detectable somatic mutations, as well as combinations of genes with detectable somatic mutations. Through case-control comparisons, we will investigate the association of somatic mutations with risk of head and neck cancers, as measured by hazard ratios and absolute risks. Additionally, within cancer cases, we will investigate the time-course of the detection of somatic mutations prior to cancer diagnosis through analyses stratified by time between sample collection and cancer diagnosis.

1. To investigate the proportion of head and neck cancers, overall and stratified by anatomic site, with detectable somatic mutations in oral rinses/buccal swabs several years prior to cancer diagnosis.
2. To investigate the risk of head and neck cancers among individuals with detectable somatic mutations in oral rinses/buccal swabs.