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The Relationship Between The Skewed X-chromosomal Inactivation Frequency And IL-21Polymorphism With The Thyroid Papillary Carcinoma

Posted on:2015-08-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:M XiaoFull Text:PDF
GTID:1224330467970713Subject:Surgery
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The female somatic cell is come from a mosaic constitute by her father and mother’s two different cells. Part of the cells contain an active maternal X chromosome and the other cells contain an active paternal X chromosome. Theoretically,the ratio of the paternal inactive X-linked allele to maternal one should be1:1, and any significant deviation from the ratio is termed as skewed X chromosome inactivation (SXCI). This process might by random, or by heredity, or is the result of second choice during his growing development. The research shows, SXCI is increased by the ages, and is relationship with a lot of disease such as carcinoma of ovary, breast cancer and some of autoimmune disease.The thyroid papillary carcinoma is increased with years, female patients is more than male patients, but the mortality rate in female patients is also better than male patients. We still don’t know why and how some patients get thyroid papillary carcinoma. Epidemiological survey shows the thyroid papillary carcinoma should be the result of the environment with heredity.In the present study, we want to survey the SXCI in healthy Chinese females. To determined the SXCI patterns of peripheral blood cells of the thyroid papillary carcinoma in female, after we definitude the relationship between the SXCI in thyroid papillary carcinoma tissues and peripheral blood cells.1180peripheral blood samples and49tumor tissues from thyroid papillary carcinoma patients were collected. We also collected1000peripheral blood samples from healthy volunteers in female at the same time. After extracting DNA from different samples, using Hpa II to digest, Expanding AD gene, we will get the CR value of the SXCI in the end.Results:(1) there is high relationship of the SXCI frequency between the tumor samples and the peripheral blood samples in thyroid papillary carcinoma patients.(n=48, r=0.57, P<0.01)(2)when CR≥3is adopted as a criterion, The SXCI frequency in thyroid papillary carcinoma female patients is increased significantly than healthy females, the result is22.0%(243/1107) and13.1%(118/902)(P=0.002). However, when CR≥10is adopted as a criterion, the result is6.4%(71/1107) and4.8%(43/902)(P=0.19), no different between them.(3) no matter when CR≥3or CR≥10is adopted as a criterion, the, The SXCI frequency in young thyroid papillary carcinoma female patients (≤45years old) is increased significantly than healthy females. However, we can not find significant different of the SXCI frequency between the old thyroid papillary carcinoma female patients (>45years old) and healthy females.(4) when CR≥3is adopted as a criterion, the SXCI frequency of the thyroid papillary microcarcinoma female patients is increased significantly than the rest of the thyroid papillary carcinoma female patients. No significant different can be found when CR≥10is adopted as a criterion.(5) no matter when CR≥3or CR≥10is adopted as a criterion, No significant different of the SXCI frequency can be found in the thyroid papillary carcinoma female patients with or without cervical lymph node metastases.Conclusions:(1) the SXCI frequency in the young (≤45years old) thyroid papillary carcinoma female patients is increased significantly than healthy females. But as they getting old (>45years old), no significant different can be found. This shows, SXCI frequency might be relationship with the young (<45years old) thyroid papillary carcinoma female patients. High SXCI frequency with high risk of getting thyroid papillary carcinoma.(2) The SXCI frequency of the thyroid papillary microcarcinoma female patients is increased significantly than the other thyroid papillary carcinoma, but the SXCI frequency of both of them are more than the healthy females. This shows that high SXCI frequency will bring more thyroid papillary microcarcinoma.(3) there might be no relationship between the SXCI frequency in the thyroid papillary carcinoma female patients with or without cervical lymph node metastases. Polymorphisms in Interleukin (IL)-21have been studied in some cancers, but the association between IL-21polymorphisms and thyroid cancer has been investigated infrequently. This case-control study examined the contribution of five tagSNPs (rs12508721>T, rs907715G>A, rs13143866G>A, rs2221903A>G and rs4833837A>G) in IL-21gene to the risk of developing thyroid cancer. IL-21genotypes were examined in615thyroid cancer patients and600controls in a Zhejiang population, and the associations with the risk of thyroid cancer were estimated by logistic regression. Moreover, the potential role of rs12508721C>T in thyroid cancer was further explored by biochemical assays. Compared with the rs12508721CC genotype, CT genotype had a significantly decreased risk of thyroid cancer (adjusted odds ratios [OR]=0.72;95%CI=0.57-0.94), the TT carriers had a further decreased risk of thyroid cancer (OR=0.56;95%CI=0.41-0.87). Furthermore, our quantitative real-time PCR and Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the presence of rs12508721T allele led to more IL-21expression. However, no significant difference was found in genotype frequencies for other four sites between cases and controls. These findings suggested that rs12508721polymorphism in IL-21might be a genetic modifier for the development of thyroid cancer.
Keywords/Search Tags:thyroid papillary carcinoma, female, X chromosome inactivation, skewedthyroid cancer, IL-21, Polymorphisms
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