<i>CHRN</i> variants and propensity to smoke or chew tobacco.

?<p>derived from linear regression of log transformed number of cigarettes smoked per day as outcome, respective <i>CHRN</i> variant as explanatory.</p>*<p>derived from linear regression of log transformed number of chewing events per day as outcome, respective <i>CHRN</i> variant as explanatory.</p>$<p>Base model included age, sex, center and case-control status.</p><p>significant p- values are indicated in bold.</p

<i>CHRN</i> variants and risk of oral cancer.

<p>Panel A shows the association between rs16969968 and oral cancer; Panel B shows the association between rs578776 and oral cancer. Forest plot represents odds ratios derived from the log additive multivariate model adjusted for age, sex, level of education and center, as appropriate.</p

Association between <i>ADH</i> & <i>ALDH2</i> variants and risk of oral cancer.

*<p>Odds ratios were derived from log additive model adjusted for age, sex, tobacco exposures and center.</p><p>P indicates p-value for heterogeneity.</p

Description of study group.

?<p>adjusted for age, sex, level of education and center.</p>$<p>Attributable fraction, expressed as percentage. Calculated using the formula p(ec)x (OR-1)/OR, where p(ec) is the proportion of exposed among cases.</p

Distribution of <i>MYD88</i> L265P allele fractions in samples from patients with familial Waldenström Macroglobulinemia prior to or after immortalization by EBV, and in lymphoblastoid lines derived from patients with lung cancer.

<p>Distribution of <i>MYD88</i> L265P allele fractions in samples from patients with familial Waldenström Macroglobulinemia prior to or after immortalization by EBV, and in lymphoblastoid lines derived from patients with lung cancer.</p

Genomic analysis of head and neck cancer cases from two high incidence regions

<div><p>We investigated how somatic changes in HNSCC interact with environmental and host risk factors and whether they influence the risk of HNSCC occurrence and outcome. 180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and South America underwent targeted sequencing (14 genes) and evaluation of copy number alterations (SCNAs). <i>TP53</i>, <i>PIK3CA</i>, <i>NOTCH1</i>, <i>TP63</i> and <i>CDKN2A</i> were the most frequently mutated genes. Cases were characterized by a low copy number burden with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with low SCNAs showed an improved overall survival. We found significant correlations with decreased overall survival between focal amplified regions 4p16, 10q22 and 22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our cases showed an association to both environmental exposures and clinical characteristics. We confirmed that somatic copy number alterations are an important predictor of HNSCC overall survival.</p></div

Workflow of processing and analysis of HNSCC samples from the three different studies.

<p>QC for copy number evaluation: Quality control of samples based on signal to noise ratio>5.0. Maps show estimated age-standardized incidence rates for HNSCC (other pharynx sites) in Europe and South America. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref031" target="_blank">31</a>].</p

Integrative cluster analysis plot.

<p>Cases are grouped by mutation and SCNA status. Top panel: only significant clustering genes are shown (0 = non-mutated, 1 = mutated), middle panel: SCNAs. Amplified (red) and deleted (blue) chromosomal regions. Altered regions are arranged vertically and sorted by genomic locus, with chromosome 1 at the top of the panel and chromosome 22 at the bottom, lower panel: colour coded clinical and epidemiological characteristics.</p

OncoPrint diagram of mutational frequencies and types of alterations of the 14 genes sequenced.

<p>Only altered samples are shown. Rows are sorted based on the frequency of the alterations in all samples and columns are sorted to visualize the mutual exclusivity across genes. Frequency of mutations for the following Head and Neck cancer publications are shown: Head & Neck (TCGA)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref010" target="_blank">10</a>], Head & Neck (JHU)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref039" target="_blank">39</a>], Head & Neck (Broad)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref032" target="_blank">32</a>], Head & Neck (MDA)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref040" target="_blank">40</a>], Head & Neck (MSKCC)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191701#pone.0191701.ref041" target="_blank">41</a>]. NA: Not available.</p

Kaplan-Meier curves showing overall survival outcome for nodal status, significant focal copy number alterations in 22q11.2,15q22 and 12p12 regions associated to smoking and advanced stage, amplification in 4p16.3 and for the three SCNAs clusters.

<p>Kaplan-Meier curves showing overall survival outcome for nodal status, significant focal copy number alterations in 22q11.2,15q22 and 12p12 regions associated to smoking and advanced stage, amplification in 4p16.3 and for the three SCNAs clusters.</p