The excess risk of cancer observed in patients with type 2 diabetes (T2DM) may have been influenced by detection bias. The aim of this study was to examine the real association by evaluating time-varying site-specific cancer risks in newly diagnosed T2DM patients. A total of 51,324 registered cancer-free individuals newly diagnosed with T2DM between 2004 and 2014 were linked with the Shanghai Cancer Registry and the Vital Statistics through September 2015. A total of 2920 primary, invasive cancer cases were identified during 325,354 person-years period. Within 1 year following diabetes onset, participants with T2DM had higher risks of total, lung and rectal cancer in men and total, liver, pancreas, thyroid, breast and uteri cancer in women. Thereafter the incidence for overall cancer decreased and then increased along with follow-up time, with the upward trend varying by cancer, suggesting potential detection bias. After the initial 1-year period, standardized incidence ratios (SIR) and 95% CIs for overall cancer were 0.80 (95% CI 0.76–0.85) in men and 0.93 (95% CI 0.88–0.99) in women, but a higher risk of breast and thyroid cancers were observed in women, with SIR and 95% CI being 1.13 (1.01, 1.28) and 1.37 (1.11, 1.63), respectively. Our results suggest that T2DM patients are at higher risk of certain cancers; this risk particularly increases shortly after diabetes diagnosis, which is likely to be due to detection bias caused by increased ascertainment. Prevention of female breast and thyroid cancers should be paid attention in Chinese individuals with T2DM.
Yuan Fang, Xuehong Zhang, Huilin Xu, Stephanie A Smith-Warner, Dongli Xu, Hong Fang and Wang Hong Xu
Xiao-Ping Qi, Jian-Zhong Peng, Xiao-Wei Yang, Zhi-Lie Cao, Xiu-Hua Yu, Xu-Dong Fang, Da-Hong Zhang and Jian-Qiang Zhao
Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.
This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family.
Summary and Conclusions
This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.