Objective Thyroid cancer incidence and diagnostic x-ray exposures, particularly CT scans and nuclear medicine examinations have increased substantially in the United States. However, very few epidemiologic studies have directly investigated their associations. Methods A population-based case-control study was conducted in Connecticut in 2010–2011 including 462 histologically confirmed incident thyroid cancer cases and 498 population-based controls. Multivariate unconditional logistic regression models were used to estimate the associations between diagnostic x-rays and risk of thyroid cancer controlling for potential confounding factors. Results Exposure to any diagnostic x-rays was associated with an increased risk of well-differentiated thyroid microcarcinoma (tumor size ≤10 mm, OR=2.76, 95%CI: 1.31–5.81). The highest risk increase occurred with nuclear medicine examinations (excluding cardiology tests and thyroid uptake studies; OR=5.47, 95%CI: 2.10–14.23), followed by chest CT scans (OR=4.30, 95%CI: 1.66–11.14), head and neck CT scans (OR=3.88, 95%CI: 1.75–8.63), upper gastrointestinal series (OR=3.56, 95%CI: 1.54–8.21), lower gastrointestinal series (OR=3.29, 95%CI: 1.41–7.66), kidney x-rays involving dye injection into a vein or artery (OR=3.21, 95%CI: 1.20–8.54), mammograms (OR=2.95, 95%CI: 1.14–7.61), chest x-rays (OR=2.93, 95%CI: 1.37–6.29), and abdomen CT scans (OR=2.54, 95%CI: 1.02–6.30). No significant associations were found between these imaging modalities and thyroid tumors larger than 10 mm. Conclusions This study provides the first direct evidence that CT scans and nuclear medicine examinations are associated with an increased risk of thyroid cancer. The novel finding that an array of diagnostic x-ray procedures are associated thyroid microcarcinomas warrants further investigation.

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Radiation exposure is a well-documented risk factor for thyroid cancer; diagnostic imaging represents an increasing source of exposure. Germline variations in DNA repair genes could increase risk of developing thyroid cancer following diagnostic radiation exposure. No studies have directly tested for interaction between germline mutations and radiation exposure. Using data and DNA samples from a Connecticut population-based case-control study performed in 2010 to 2011, we genotyped 440 cases of incident thyroid cancer and 465 population-based controls for 296 SNPs in 52 DNA repair genes. We used multivariate unconditional logistic regression models to estimate associations between each SNP and thyroid cancer risk, as well as to directly estimate the genotype-environment interaction between each SNP and ionizing radiation. Three SNPs were associated with increased risk of thyroid cancer and with thyroid microcarcinoma: rs2708896, rs10951937, and rs12769288. No SNPs were associated with increased risk of larger tumor (>10 mm) in the additive model. The gene-environment interaction analysis yielded 24 SNPs with < 0.05 for all thyroid cancer, 12 SNPs with < 0.05 for thyroid microcarcinoma, and 5 SNPs with < 0.05 for larger tumors. Germline variants in DNA repair genes are associated with thyroid cancer risk and are differentially associated with thyroid microcarcinoma and large tumor size. Our study provides the first evidence that germline genetic variations modify the association between diagnostic radiation and thyroid cancer risk. Thyroid microcarcinoma may represent a distinct subset of thyroid cancer. The effect of diagnostic radiation on thyroid cancer risk varies by germline polymorphism. .

Efficient methods to immobilize small molecules under continuous-flow microfluidic conditions would greatly improve label-free molecular interaction studies using biosensor technology. At present, small-molecule immobilization chemistries require special conditions and in many cases must be performed outside the detector and microfluidic system where real-time monitoring is not possible. Here, we have developed and optimized a method for on-chip bioorthogonal chemistry that enables rapid, reversible immobilization of small molecules with control over orientation and immobilization density, and apply this technique to surface plasmon resonance (SPR) studies. Immobilized small molecules reverse the orientation of canonical SPR interaction studies, and also enable a variety of new SPR applications including on-chip assembly and interaction studies of multicomponent structures such as functionalized nanoparticles, and measurement of bioorthogonal reaction rates. We use this approach to demonstrate that on-chip assembled functionalized nanoparticles show a preserved ability to interact with their target protein, and to measure rapid bioorthogonal reaction rates with k2 > 103 M−1 s−1. This method offers multiple benefits for microfluidic biological applications, including rapid screening of targeted nanoparticles with vastly decreased nanoparticle synthetic requirements, robust immobilization chemistry in the presence of serum, and a continuous flow technique that mimics biologic contexts better than current methods used to measure bioorthogonal reaction kinetics such as NMR or UV-vis spectroscopy (e.g., stopped flow kinetics). Taken together, this approach constitutes a flexible and powerful technique for evaluating a wide variety of reactions and intermolecular interactions for in vitro or in vivo applications.