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Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

ABSTRACT: Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ?7 (0?=?"no pain" and 10?=?"worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P?=?3.45?×?10(-8); rs880143, P?=?3.45?×?10(-8); and rs7526880, P?=?4.92?×?10(-8)), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.

SUBMITTER: Reyes-Gibby CC

PROVIDER: S-EPMC5037456 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

Reyes-Gibby Cielito C CC Wang Jian J Silvas Mary Rose T MR Yu Robert K RK Hanna Ehab Y EY Shete Sanjay S

Scientific reports 20160927

Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had sev ...[more]

PMID: 27670397

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Project description:Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune modulation of the tumor microenvironment affect not only cancer progression but also pain signaling. For example, Schwann cells promote cancer cell proliferation, migration, and secretion of nociceptive mediators, whereas neutrophils are implicated in sex differences in pain in animal models of HNC. Emerging evidence supports the existence of a functional loop of cross-activation between the tumor microenvironment and peripheral nerves, mediated by a molecular exchange of bioactive contents (pronociceptive and protumorigenic) via paracrine and autocrine signaling. Brain-derived neurotrophic factor, tumor necrosis factor α, legumain, cathepsin S, and A disintegrin and metalloprotease 17 expressed in the HNC microenvironment have recently been shown to promote HNC pain, further highlighting the importance of proinflammatory cytokines, neurotrophic factors, and proteases in mediating HNC-associated pain. Pronociceptive mediators, together with nerve injury, cause nociceptor hypersensitivity. Oncogenic, pronociceptive mediators packaged in cancer cell-derived exosomes also induce nociception in mice. In addition to increased production of pronociceptive mediators, HNC is accompanied by a dampened endogenous antinociception system (e.g., downregulation of resolvins and µ-opioid receptor expression). Resolvin treatment or gene delivery of µ-opioid receptors provides pain relief in preclinical HNC models. Collectively, recent studies suggest that pain and HNC progression share converging mechanisms that can be targeted for cancer treatment and pain management.

Project description:ObjectivesHigher physical activity (PA) levels are associated with better quality of life in people with head and neck cancer (HNC). Despite this positive association, most individuals with these cancer types have a sedentary or low-activity lifestyle. Limited knowledge exists regarding the factors that influence PA in this group. Therefore, we reviewed and mapped the available literature on factors that may influence PA in people with HNC.DesignWe conducted a scoping review based on the framework of Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline extension for scoping reviews.Data sourcesCINHAL, the Cochrane Library, EMBASE, PsycINFO, MEDLINE and Scopus were searched from inception to July 2023.Eligibility criteriaWe included qualitative and quantitative studies that stated factors such as barriers, facilitators, beliefs, perceptions and views influencing PA in individuals with HNC. Furthermore, views and recommendations of healthcare professionals involved in the care of people affected by HNC and researchers in this domain were eligible for data extraction.Data extraction and synthesisData were extracted and synthesised by one reviewer according to the predefined items including characteristics, barriers, facilitators, beliefs, perceptions and views of people being affected and views and recommendations of experts. Quantitative data were charted descriptively, and qualitative data were analysed and summarised using a basic content analysis approach.ResultsOf the 1351 publications, we included 19 in our review. Publications mainly focused on barriers to PA, with some studies reporting facilitators and collecting data on patients' and healthcare professionals' views on PA. Most research teams made recommendations for promoting PA in people with HNC.Characteristics associated with activity levels included age, cancer type and stage, morbidity level and attitude towards being active. Prevalent barriers consisted of health-related factors, including fatigue, pain and nutritional issues, alongside personal and environmental impediments such as time constraints, lack of interest or motivation. Facilitating factors for PA included perceived or experienced mental and health-related benefits. Consensus among patients, healthcare professionals and researchers highlighted the necessity for enhanced information and education, emphasising individualised approaches to promote PA throughout the cancer continuum.ConclusionsNumerous factors affect PA in individuals with HNC. Future research should concentrate on screening and addressing risk factors for sedentary behaviour and activity barriers and on optimal design and delivery of interventions to incorporate PA promotion into the care pathway.

Dataset Information

Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

Publications

Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

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