The Role Of Pregnancy, Breast-feeding And Skewed X Chromosome On Autoimmune Thyroid Disease And Papillary Thyroid Cancer In Women

ObjectiveAutoimmune thyroid diseases (AITD), including Graves'disease (GD) and Hashimoto's thyroiditis (HT), and papillary thyroid carcinoma (PTC) are more common in female than in male. The cause of the female preponderance has not been understood. The objective of this study was to explore the contribution of reproductive factors, such as times of pregnancy, breast-feeding and skewed X chromosome inactivation (XCI) pattern on AITD and PTC.Methods1. Six hundred married women who were diagnosed as GD (n=144), HT (n=156), PTC (n=140), and healthy control (n=160) at clinic of Endocrinology, PUMC hospital were enrolled from Apr.1st 2009 to Dec.31st 2009. Data were collected and analyzed by thyroidists on personal and family history of thyroid disease, autoimmune diseases, and cancer, radio and toxic exposure, smoking and drinking, times of pregnancy, miscarriage, parity, and duration of breast feeding, etc.2. Serum levels of FT4, FT3 and TSH and thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and thyrotropin receptor antibody (TRAb) were measured.3. CAG repeats copies of exon 1 of HUMARA gene from the peripheral blood genomic DNA of married women with GD (n=51), HT (n=47), PTC (n=44), and healthy control (n=44) were detected by PCR assay, also, PCR technique was applied to assess XCI pattern after digestion of DNA with methylation-sensitive restriction endonucleases Hpaâ…¡and Hhaâ… . Results1. Times of pregnancy:There were significant difference in times of pregnancy among the patients with GD, TH, PTC compared with control. The percentage of>=3->=5 times of pregnancy of the women with GD was significant higher than that of healthy control. However, there were no significant difference between GD and HT, PTC and healthy control.2. Duration of breast-feeding:There were significant difference of breast-feeding in GD, TH, PTC and healthy control who breast fed babies>=6 to>=24 months. The percentage of>=6 to>=24 months breast feeding of GD was significant higher than that of healthy control. However, there was no significant difference between GD and HT groups.3. Results strongly indicated that an increasing risk of GD associated with increasing times of pregnancy and duration of breast feeding by Multinomial logistic regression anaylsis. For women whose times of pregnancy was> 3(compared with those>= 2), the OR and 95%CIs for risk of GD were as follows:times of pregnancy>=3, OR 2.13 (95%CI 1.00-4.53);>=4:OR 3.53,95%CI1.185-10.50;>=5:OR 5.53 (95%CI 1.70-17.99). F or women whose times of pregnancy was>= 4, OR for risk of HT and PTC was 3.30 (95%CI 1.19-9.14), and 2.39(95%CI, 1.1-9.58),respectively.4. For women whose duration of breast feeding was>= 12 months(compared with those=...