Cannon, Ashley

Abstract Introduction: An inverse association between alcohol consumption and risk of renal cell carcinoma (RCC) is well reported in the literature. Despite this, no investigators have explored the potential for effect modification of this association by genetic variations in enzymes that metabolize alcohol. Motivated by this, we conducted a pilot investigation of the role of genetic variation in the alcohol dehydrogenase genes (ADH) as an effect modifier of the association of alcohol and RCC risk. Methods: We analyzed data on 121 RCC cases and 121 controls. Cases were prospectively collected as part of our Renal Registry in the Department of Urology. Controls were recruited through the Family Medicine and frequency matched to cases on age, gender and state of residence. We collected detailed risk factor data (self-report questionnaire) as well as a DNA sample on cases and controls. We utilized Sequenome analysis to determine presence of published SNPs in the ADH gene cluster (ADH1-7). We employed logistic regression with interaction terms as well as stratified analyses to evaluate effect modification by genetic variants in the ADH gene cluster on the association of alcohol consumption and RCC risk. Results: Compared to non-drinkers, those that consumed alcohol above the median experienced a lowering in RCC risk (OR=0.80; 95% CI 0.5 to 1.43). We observed evidence of interactions with 6 SNPs in the ADH gene (p-values from 0.05-0.2). As an example, in stratified analysis, the inverse association strengthened in those without the minor allele present at rs1154454 in ADH7 (OR=0.56; 95% CI 0.3 to 1.0; p=0.08) while evidence of an increased in RCC risk was noted among those with the minor allele (OR=2.14; 95CI 0.8 – 5.7; p=0.1). Adjustment for age and gender did not alter our results. Conclusion: Our pilot data suggest that specific variants in the ADH gene cluster may modify the reported protective effect of alcohol consumption on RCC risk. Given the possible implications for improving our understanding of the biology of this association and informing prevention, future investigations that analyze a larger sample size and examine additional variants are warranted. Citation Format: Alexander Scott Parker, Nancy Diehl, Michelle L. Arnold, Shauna Rivera, Ashley Cannon, Kaitlynn Custer, Bradley Leibovich. Alcohol consumption, genetic variation in alcohol dehydrogenase genes, and risk of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A62.

Objective. To describe the use of an advanced genetic testing technique, whole exome sequencing, to diagnose a patient and their family with aSCN9Achannelopathy.Setting. Academic tertiary care center.Design. Case report.Case Report. A 61-year-old female with a history of acute facial pain, chronic pain, fibromyalgia, and constipation was found to have a gain of functionSCN9Amutation by whole exome sequencing. This mutation resulted in anSCN9Achannelopathy that is most consistent with a diagnosis of paroxysmal extreme pain disorder. In addition to the patient being diagnosed, four siblings have a clinical diagnosis ofSCN9Achannelopathy as they have consistent symptoms and a sister with a known mutation. For treatment, gabapentin was ineffective and carbamazepine was not tolerated. Nontraditional therapies improved symptoms and constipation resolved with pelvic floor retraining with biofeedback.Conclusion. Patients with a personal and family history of chronic pain may benefit from a referral to Medical Genetics. Pelvic floor retraining with biofeedback should be considered for patients with aSCN9Achannelopathy and constipation.