Kashin-Beck disease (KBD) is an endemic osteoarthropathy. Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer, long frost period, and large temperature differences between day and night. In particular, KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns. Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas. Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather. The epidemiological characteristics of KBD include agricultural area, early age of onset, gender equality, family aggregation, regional differences, and annual fluctuations. A series of preventive measures have been successfully taken in the past decades. National surveillance data indicate that the annual incidence of KBD is gradually declining.

  Objective  The varying environmental exposure to iodine has long been a topic of interest, particularly given the noticeable increase in the incidence of papillary thyroid carcinoma (PTC) compared to other histopathological subtypes globally. This rise in thyroid cancer incidence has been attributed to several factors, including improved detection of early tumors, a higher prevalence of modifiable individual risk factors, and differing exposure to environmental risk factors such as iodine levels. This study aims to explore the epigenetic mechanisms that promote thyroid cancer progression under excess iodine exposure.  Materials and methods  This study outlines the following strategy: (i) risk factors were identified through statistical analysis of questionnaire responses in a retrospective iatrogenic study; (ii) following the identification of risk factors, RNA sequencing was performed using tissues from iodine-adequate (IA) and iodine-excess (IE) regions; (iii) candidate hub genes were selected via bioinformatics analysis; (iv) molecular biological techniques were employed to verify the functionality of the key gene.  Results  Through careful selection, we focused on SPSB4, a ubiquitin ligase previously unreported in relation to both iodine and thyroid cancer. By optimizing the dosage of PTC cell line activities, we determined how varying iodine levels can either enhance or impair the vitality of thyroid cancer cells. As anticipated, migration and invasion assays revealed significant changes when SPSB4 function was disrupted at the critical dose of KIO3.  Conclusions  In terms of epigenetic alterations, SPSB4 emerges as a promising candidate for further investigation, particularly in understanding thyroid cancer progression and potential carcinogenesis. Moreover, E3 ubiquitin ligases, including SPSB4, play a role in orchestrating adipose thermogenesis to maintain body temperature during cold stimuli. This study could also shed light on the influence of iodine on thermogenesis mediated by SPSB4 under cold conditions, while suggesting future exploration of SPSB4's effects on thyroid cancer in colder regions.