Joni L. Rutter

Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model—Recommendations From an NIH Workshop

Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene‐environment interaction remain a challenge and have had limited success to date. Given the current state‐of‐the‐science, NIH sought input on ways to accelerate investigations of gene‐environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene‐environment interaction studies. Participants of the NIH Gene‐Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene‐environment interactions. Further, participants also emphasized the continued need for high‐quality measures of environmental exposures and new genomic technologies in ongoing and new studies. Genet. Epidemiol. 35: 217‐225, 2011.  © 2011 Wiley‐Liss, Inc.

Thyroid Nodules, Polymorphic Variants in DNA Repair and RET-Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan

Abstract Sigurdson, A. J., Land, C. E., Bhatti, P., Pineda, M., Brenner, A., Carr, Z., Gusev, B. I., Zhumadilov, Z., Simon, S. L., Bouville, A., Rutter, J. L., Ron, E. and Struewing, J. P. Thyroid Nodules, Polymorphic Variants in DNA Repair and RET-Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan. Radiat. Res. 171, 77–88 (2009). Risk factors for thyroid cancer remain largely unknown except for ionizing radiation exposure during childhood and a history of benign thyroid nodules. Because thyroid nodules are more common than thyroid cancers and are associated with thyroid cancer risk, we evaluated several polymorphisms potentially relevant to thyroid tumors and assessed interaction with ionizing radiation exposure to the thyroid gland. Thyroid nodules were detected in 1998 by ultrasound screening of 2997 persons who lived near the Semipalatinsk nuclear test site in Kazakhstan when they were children (1949–1962). Cases with thyroid nodules (n = 907) were frequency matched (1:1) to those without nodules by ethnicity (Kazakh or Russian), gender and age at screening. Thyroid gland radiation doses were estimated from fallout deposition patterns, residence history and diet. We analyzed 23 polymorphisms in 13 genes and assessed interaction with ionizing radiation exposure using likelihood ratio tests (LRT). Elevated thyroid nodule risks were associated with the minor alleles of RET S836S (rs1800862, P = 0.03) and GFRA1 −193C>G (rs not assigned, P = 0.05) and decreased risk with XRCC1 R194W (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009). Similar patterns of association were observed for a small number of papillary thyroid cancers (n = 25). Ionizing radiation exposure to the thyroid gland was associated with significantly increased risk of thyroid nodules (age and gender adjusted excess odds ratio/Gy = 0.30, 95% CI 0.05–0.56), with evidence for interaction by genotype found for XRCC1 R194W (LRT P value = 0.02). Polymorphisms in RET signaling, DNA repair and proliferation genes may be related to risk of thyroid nodules, consistent with some previous reports on thyroid cancer. Borderline support for gene-radiation interaction was found for a variant in XRCC1, a key base excision repair protein. Other pathways such as genes in double-strand break repair, apoptosis and genes related to proliferation should also be pursued.

Heterogeneity of risk for melanoma and pancreatic and digestive malignancies: a melanoma case-control study.

Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma‐associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies.

National Institute on Drug Abuse symposium report: drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia

The National Institute on Drug Abuse organized a symposium on drugs of abuse, dopamine, and HIV-associated neurocognitive disorders (HAND)/HIV-associated dementia (HAD) in Rockville, Maryland, October4, 2011. The purpose of this symposium was to evaluate the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. A summary of the symposium has been presented in this report.

Emerging trends in the abuse of designer drugs and their catastrophic health effects: Update on chemistry, pharmacology, toxicology and addiction potential

Foreword Over the past ten years the use of designer cathinones and designer cannabinoids has become a major public health problem. There has been an upsurge in hospital emergency room visits and calls to poison control centers reporting use and severe consequences of using these designer drugs, especially among high school and college students. The National Institute on Drug Abuse (NIDA) recently organized a symposium entitled “Emerging Trends in the Abuse of Designer Drugs and Their Catastrophic Health Effects: Update on Chemistry, Toxicology, Addiction Potential and Treatment.” Selected topics from this symposium are assembled in this proceedings volume to update the research findings in this critical area and to providehelpful information onmechanisms, pharmacology, and toxicology of these drugs. It is hoped that

A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health

In a Policy Forum, Muin Khoury and colleagues discuss research on the clinical application of genome sequencing data.