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Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

View Article: PubMed Central - PubMed

ABSTRACT

While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

No MeSH data available.


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Prevalence of key genetic aberrations in 24 black and 208 white HPV-negative patients (TCGA HNSCC cohort), 37 HPV-negative Indian patients (ICGC HNSCC cohort), 16 Indian HPV-negative patients (Krishnan cohort), and 60 patients from Singapore of unidentified HPV status (Vettore cohort) [1, 16–18]PIK3CA and NOTCH1 mutations only are reported for the Krishnan cohort. NOTCH1 mutation prevalence only is reported for the Vettore cohort. * indicates significant differences between white and black TCGA cohorts. † indicates significant differences between white TCGA and Indian ICGC cohorts. ‡ indicates significant differences between white TCGA and Vettore cohorts. # indicates significant differences between white TCGA and Krishnan cohorts.
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Figure 3: Prevalence of key genetic aberrations in 24 black and 208 white HPV-negative patients (TCGA HNSCC cohort), 37 HPV-negative Indian patients (ICGC HNSCC cohort), 16 Indian HPV-negative patients (Krishnan cohort), and 60 patients from Singapore of unidentified HPV status (Vettore cohort) [1, 16–18]PIK3CA and NOTCH1 mutations only are reported for the Krishnan cohort. NOTCH1 mutation prevalence only is reported for the Vettore cohort. * indicates significant differences between white and black TCGA cohorts. † indicates significant differences between white TCGA and Indian ICGC cohorts. ‡ indicates significant differences between white TCGA and Vettore cohorts. # indicates significant differences between white TCGA and Krishnan cohorts.

Mentions: Despite the majority of HNSCCs occurring in non- American populations (incidence rate of 60,000 annually in the US vs 490,000 annually in the rest of world), NGS studies have been limited to cohorts of primarily European ancestry and not other ethnic groups or epidemiologic populations. TCGA and the International Cancer Genome Consortium (ICGC) reported sequencing for cohorts of HNSCC patients in the United States and India, respectively [1, 18]. In the TCGA cohort, the majority of these patients were white (242/279, 86.7%), with only 25/279 (9.0%) black. Different mutational profiles were evidenced between black and white HPV-negative patients (Figure 3). For instance, black patients have significantly higher rates of BIRC2/3 amplification compared to white HNSCC patients in this study (25.0% vs 4.3%, p < 0.001). Although they do not reach statistical significance, blacks also trend toward decreased EGFR (4.2% vs 13.5%, p = 0.19) and increased FGFR1 (16.7% vs 9.1%, p = 0.24) amplification. Other genetic aberrations were similar between these two ethnic groups [77, 78].


Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine
Prevalence of key genetic aberrations in 24 black and 208 white HPV-negative patients (TCGA HNSCC cohort), 37 HPV-negative Indian patients (ICGC HNSCC cohort), 16 Indian HPV-negative patients (Krishnan cohort), and 60 patients from Singapore of unidentified HPV status (Vettore cohort) [1, 16–18]PIK3CA and NOTCH1 mutations only are reported for the Krishnan cohort. NOTCH1 mutation prevalence only is reported for the Vettore cohort. * indicates significant differences between white and black TCGA cohorts. † indicates significant differences between white TCGA and Indian ICGC cohorts. ‡ indicates significant differences between white TCGA and Vettore cohorts. # indicates significant differences between white TCGA and Krishnan cohorts.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979591&req=5

Figure 3: Prevalence of key genetic aberrations in 24 black and 208 white HPV-negative patients (TCGA HNSCC cohort), 37 HPV-negative Indian patients (ICGC HNSCC cohort), 16 Indian HPV-negative patients (Krishnan cohort), and 60 patients from Singapore of unidentified HPV status (Vettore cohort) [1, 16–18]PIK3CA and NOTCH1 mutations only are reported for the Krishnan cohort. NOTCH1 mutation prevalence only is reported for the Vettore cohort. * indicates significant differences between white and black TCGA cohorts. † indicates significant differences between white TCGA and Indian ICGC cohorts. ‡ indicates significant differences between white TCGA and Vettore cohorts. # indicates significant differences between white TCGA and Krishnan cohorts.
Mentions: Despite the majority of HNSCCs occurring in non- American populations (incidence rate of 60,000 annually in the US vs 490,000 annually in the rest of world), NGS studies have been limited to cohorts of primarily European ancestry and not other ethnic groups or epidemiologic populations. TCGA and the International Cancer Genome Consortium (ICGC) reported sequencing for cohorts of HNSCC patients in the United States and India, respectively [1, 18]. In the TCGA cohort, the majority of these patients were white (242/279, 86.7%), with only 25/279 (9.0%) black. Different mutational profiles were evidenced between black and white HPV-negative patients (Figure 3). For instance, black patients have significantly higher rates of BIRC2/3 amplification compared to white HNSCC patients in this study (25.0% vs 4.3%, p < 0.001). Although they do not reach statistical significance, blacks also trend toward decreased EGFR (4.2% vs 13.5%, p = 0.19) and increased FGFR1 (16.7% vs 9.1%, p = 0.24) amplification. Other genetic aberrations were similar between these two ethnic groups [77, 78].

View Article: PubMed Central - PubMed

ABSTRACT

While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

No MeSH data available.


Related in: MedlinePlus