Molecular Epidemiology of Neuropathic Pain in Head and Neck Cancer

描述（由申请人提供）：疼痛通常是头颈癌的最初迹象之一。头颈癌疼痛可能是由于疾病本身（肿瘤）或作为治疗的结果。高达80%的头颈癌患者在治疗期间报告疼痛，约36%的患者在治疗后疼痛持续存在。慢性疼痛会导致长期痛苦和生活质量下降。神经性疼痛，特别是，仍然是一个主要的临床问题，因为现有的镇痛药往往无效，并有严重的副作用。因此，本研究的目标是对2400例头颈癌患者进行全基因组（730,525个snp）分析，以确定慢性疼痛的分子/遗传基础，并特别强调验证遗传机制在从急性疼痛到慢性疼痛（伤害性与神经性）转变中的作用。具体目标是；目的1：对2400例头颈部鳞状细胞癌患者进行遗传分析，以确定与慢性疼痛（神经性与伤害性）发展相关的潜在新基因变异。假设1：潜在的新基因变异也可能作为疼痛的治疗靶点，将通过全基因组SNP扫描来识别。目的2：建立头颈癌患者队列，确定行为、流行病学、生物学和临床因素在预测这些患者慢性疼痛（神经性/伤害性）发展中的独立影响。假设1：慢性疼痛的发展会因癌症治疗（手术、化疗、放疗）、行为、流行病学和临床因素而异。目标3：进行探索性基因-基因和基因-治疗（癌症治疗类型）相互作用分析，这将有助于在遗传风险特征和治疗的基础上确定慢性疼痛（神经性与伤害性）发展风险最高的个体（例如，我们将测试每个SNP的风险等位基因与详细治疗信息的关联）。疼痛将通过自我报告和定量感觉测试以及行为，遗传，临床和流行病学因素的评估进行纵向评估。我们期望本研究的新发现将为慢性神经性疼痛的遗传机制提供新的见解，并可能为开发新的治疗慢性神经性疼痛的药物提供新的信息。

DESCRIPTION (provided by applicant): Pain is often one of the first signs of head and neck cancer. Head and neck cancer pain may be due to the disease itself (tumor) or as a consequence of therapy. Up to 80% of patients with head and neck cancer report pain during treatment and for some 36%, pain persists beyond treatment. Chronic pain leads to prolonged suffering and reduced quality of life. Neuropathic pain, in particular, remains a major clinical problem since existing analgesics are often ineffective and with serious side-effects. Therefore, the goal of this proposal is to perform genome-wide (730,525SNPs) analyses on 2400 patients with head and neck cancer to determine the molecular/genetic basis of chronic pain, with a specific emphasis on validating the role of genetic mechanisms in the transition from acute pain to chronic pain (nociceptive versus neuropathic). The specific aims are; AIM 1: To perform genetic analyses on 2400 patients with squamous cell carcinoma of the head and neck in order to identify potentially novel gene variants associated with the development of chronic pain (neuropathic versus nociceptive). Hypothesis 1: Potentially novel genetic variants that may also serve as therapeutic targets for pain will be identified using a genome-wide SNP scan. AIM 2: To establish a cohort of head and neck cancer patients and determine the independent influence of behavioral, epidemiological, biological, and clinical factors in predicting the development of chronic pain (neuropathic/nociceptive) in these patients. Hypothesis 1: The development of chronic pain will vary by cancer treatment (surgery, chemotherapy, radiotherapy) and behavioral, epidemiological, and clinical factors. AIM 3: To perform exploratory gene-gene and gene-treatment (type of cancer treatment) interaction analyses that will help identify individuals at highest risk for the development of chronic pain (neuropathic versus nociceptive) on the basis of their genetic risk profiles and treatment (e.g. we will test th risk allele of each SNP for its association with detailed treatment information). Pain will be longitudinally assessed by self-report and quantitative sensory testing along with assessment of behavioral, genetic, clinical and epidemiological factors. We expect that new findings from this proposal will provide insight into the genetic mechanisms of chronic pain development and may provide novel information, which could lead to the development of new therapeutic agents for chronic neuropathic pain.