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E Giustarini, A Pinchera, P Fierabracci, M Roncella, L Fustaino, C Mammoli and C Giani

Background: Previous studies have demonstrated a high prevalence of thyroperoxidase antibodies (TPOAb) and autoimmune hypothyroidism in breast cancer (BC). These studies have been performed in BC patients generally 20–30 days after mastectomy. It is known that stress may have an influence on the immune system and a relation between stressful events and the onset or worsening of autoimmune thyroid disorders has been reported by several authors. The aim of the study was to evaluate the prevalence of autoimmune thyroid disease in patients with nodular breast disease selected for surgery before any treatment. Our hypothesis was that the high prevalence of thyroid autoimmune disorders in BC is independent of stressful events represented by surgery and/or anaesthetic procedures.

Methods: Our series included 61 consecutive women aged 52.8 ± 10.2 yrs (mean age ± s.d.) with nodular breast disease selected for breast surgery: 36 out of 61 of them (59%) had BC and 25 out of 61 had benign breast disease (BBD). Controls included 100 healthy age-matched women. All patients and control subjects were submitted to clinical, ultrasound thyroid evaluation and serum-free thyroxine (FT4), serum-free tri-iodothyronine (FT3), TSH, TPOAb and thyroglobulin antibodies (TgAb) determination.

Results: Mean FT3, FT4 and TSH concentration showed no differences between BC patients, BBD patients and controls. The prevalence of TPOAb in BC patients (12/36: 33.33%) was significantly higher than in BBD patients (5/25: 20%) (P < 0.01) and in controls (8/100: 8%) (P < 0.01). Similarly, the prevalence of TgAb in BC patients was 12 out of 36 (33.33%) significantly higher than that detected in BBD patients (4/25: 16%) (P < 0.01) and in controls (12/100: 12%) (P < 0.01). Of the 36 BC patients, 20 showed a diffuse hypoechogenicity of the thyroid gland to ultrasound evaluation, significantly higher than in BBD (7/25: 28%) (P = 0.03). Of the 20 BC patients who showed a hypoechogenic pattern of thyroid gland, 10 (50%) were associated with antithyroid antibodies positivity (TAb). This finding was present in two of seven BBD (28.57%) (P < 0.0001). Only two controls showed focal hypoechogenicity of the thyroid gland. Generally, 24 out of 36 (66.7%) of BC and 9 out of 25 (36%) of BBD (P = 0.02) had signs of thyroid autoimmunity consistent with the hypoechogenic pattern of thyroid gland associated or not with TAb; 2 out of 36 (5.55%) of BC and 1 out of 25 (4%) of BBD patients had autoimmune hypothyroidism and no hypothyroidism was found in controls.

Conclusions: The results of this study confirm the strong relation between thyroid autoimmunity and BC. This finding is independent of stressful events represented by surgery or anaesthetic procedures. The present data call attention to the usefulness of screening for autoimmune thyroid disorders in patients with nodular breast disease selected for surgery.

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C Holzapfel, N Klopp, H Grallert, C Huth, C Gieger, C Meisinger, K Strassburger, G Giani, H E Wichmann, H Laumen, H Hauner, C Herder, W Rathmann and T Illig

Objective: The aim of our study was to determine the variant pattern of the leukemia-associated Rho guanine nucleotide exchange factor (LARG, or ARHGEF12) gene and investigate whether LARG variants are associated with diabetes mellitus type 2 (T2DM), the metabolic syndrome (MetS), or related parameters such as insulin sensitivity in German Caucasians.

Design: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in the 55–74-year-old individuals of the population-based German Caucasian Cooperative Health Research in the region of Augsberg (KORA) survey 4 (S4).

Methods: Sequencing of Tyr1306Cys, which was of functional relevance in Pima Indians, in 48 randomly selected individuals and genotyping of 11 additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r2≥0.8) were established and each block was statistically analyzed for association with metabolic traits. The association with T2DM and the MetS was analyzed by logistic regression in 1462 subjects, and HOMA-IR (homeostasis model assessment of insulin resistance) as a measure of insulin sensitivity was analyzed by the Kruskal–Wallis test in 1346 fasting subjects.

Results: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians, was not found in the KORA S4 population. Statistical analysis yielded no significant associations (P>0.05) between the analyzed LARG variants and T2DM, the MetS, or related parameters such as insulin sensitivity.

Conclusions: Caucasian individuals and Pima Indians differ in their genetic variance pattern in the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity, or the MetS.