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      Deciphering the Risk of Developing Second Primary Thyroid Cancer Following a Primary Malignancy—Who Is at the Greatest Risk?

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          Abstract

          Simple Summary

          Associations between thyroid cancer and breast cancer have been elucidated, in that patients with breast cancer have a greater risk of developing subsequent thyroid cancer. However, not much is known about the relationship other primary cancers and subsequent thyroid cancer. In this review, we completed a thorough review of the existing literature to understand the relationship between primary cancers and second primary thyroid cancer (SPTC). Our findings suggest that surveillance protocols should be considered for patients at a higher risk of SPTC, including those with primary breast, renal cell, basal cell, and ovarian cancers who are female and/or Caucasian.

          Abstract

          Background: It is critical to understand factors that may contribute to an increased risk of SPTC in order to develop surveillance protocols in high-risk individuals. This systematic review and meta-analysis will assess the association between primary malignancy and SPTC. Methods: A search of PubMed and Embase databases was completed in April 2020. Inclusion criteria included studies that reported the incidence or standardized incidence ratio of any primary malignancy and SPTC, published between 1980–2020. The PRISMA guidelines were followed and the Newcastle–Ottawa Scale was used to assess quality of studies. Results: 40 studies were included, which were comprised of 1,613,945 patients and 15 distinct types of primary cancers. In addition, 4196 (0.26%) patients developed SPTC following a mean duration of 8.07 ± 4.39 years. Greater risk of developing SPTC was found following primary breast (56.6%, 95%CI, 44.3–68.9, p < 0.001), renal cell (12.2%, 95%CI, 7.68–16.8, p < 0.001), basal cell (7.79%, 95%CI, 1.79–13.7, p = 0.011), and ovarian cancer (11.4%, 95%CI, 3.4–19.5, p = 0.005). SPTC patients were more likely to be females (RR = 1.58, 95%CI, 1.2–2.01, p < 0.001) and Caucasians ( p < 0.001). Conclusions: Surveillance protocols should be considered for patients at a higher risk of SPTC, including those with primary breast, renal cell, basal cell and ovarian cancers who are female and/or Caucasian.

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          Current thyroid cancer trends in the United States.

          We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable, we argued that the increased incidence represented overdiagnosis. To determine whether thyroid cancer incidence has stabilized. Analysis of secular trends in patients diagnosed with thyroid cancer, 1975 to 2009, using the Surveillance, Epidemiology, and End Results (SEER) program and thyroid cancer mortality from the National Vital Statistics System. Nine SEER areas (SEER 9): Atlanta, Georgia; Connecticut; Detroit, Michigan; Hawaii; Iowa; New Mexico; San Francisco-Oakland, California; Seattle-Puget Sound, Washington; and Utah. Men and women older than 18 years diagnosed as having a thyroid cancer between 1975 and 2009 who lived in the SEER 9 areas. None. Thyroid cancer incidence, histologic type, tumor size, and patient mortality. RESULTS Since 1975, the incidence of thyroid cancer has now nearly tripled, from 4.9 to 14.3 per 100,000 individuals (absolute increase, 9.4 per 100,000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). Virtually the entire increase was attributable to papillary thyroid cancer: from 3.4 to 12.5 per 100,000 (absolute increase, 9.1 per 100,000; RR, 3.7; 95% CI, 3.4-4.0). The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100,000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100,000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100,000). There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.
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            International patterns and trends in thyroid cancer incidence, 1973-2002.

            During the past several decades, an increasing incidence of thyroid cancer has been reported in many parts of the world. To date, no study has compared the trends in thyroid cancer incidence across continents. We examined incidence data from cancer incidence in five continents (CI5) over the 30-year period 1973-2002 from 19 populations in the Americas, Asia, Europe, and Oceania. Thyroid cancer rates have increased from 1973-1977 to 1998-2002 for most of the populations except Sweden, in which the incidence rates decreased about 18% for both males and females. The average increase was 48.0% among males and 66.7% among females. More recently, the age-adjusted international thyroid cancer incidence rates from 1998 to 2002 varied 5-fold for males and nearly 10-fold for females by geographic region. Considerable variation in thyroid cancer incidence was present for every continent but Africa, in which the incidence rates were generally low. Our analysis of published CI5 data suggests that thyroid cancer rates increased between 1973 and 2002 in most populations worldwide, and that the increase does not appear to be restricted to a particular region of the world or by the underlying rates of thyroid cancer.
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              CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway

              Circular RNAs (circRNAs) are reported to act as important regulators in cancers. CircRNA RAPGEF5 (cRAPGEF5) is derived from exons 2-6 of the RAPGEF5 gene and may promote papillary thyroid cancer progression. However, the role of cRAPGEF5 in renal cell carcinoma (RCC) remains unclear. In this study, we found cRAPGEF5 to be significantly downregulated in RCC tissues. Among 245 RCC cases, cRAPGEF5 downregulation correlated positively with aggressive clinical characteristics and independently predicted poor overall survival and recurrence-free survival. Functional assays demonstrated that cRAPGEF5 suppresses RCC proliferation and migration in vitro and in vivo. Mechanistically, RNA Immunoprecipitation and circRNA in vivo precipitation assays showed that cRAPGEF5 functions as a sponge of oncogenic miR-27a-3p, which targets the suppressor gene TXNIP. Interactions between miR-27a-3p and cRAPGEF5 or TXNIP were confirmed by dual-luciferase reporter assays. In conclusion, cRAPGEF5 plays a role in suppressing RCC via the miR-27a-3p/TXNIP pathway and may serve as a promising prognostic biomarker and novel therapeutic target for RCC patients.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                19 March 2021
                March 2021
                : 13
                : 6
                : 1402
                Affiliations
                [1 ]School of Medicine, Tulane University, New Orleans, LA 70032, USA; ltrinh1@ 123456tulane.edu (L.N.T.); acrawfo2@ 123456tulane.edu (A.R.C.)
                [2 ]Department of Surgery, Tulane University, New Orleans, LA 70032, USA; mhussein1@ 123456tulane.edu (M.H.H.); mzerfaoui@ 123456tulane.edu (M.Z.)
                [3 ]Department of Histology and Cell Biology, Suez Canal University, 41523 Ismailia, Egypt
                [4 ]Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; grego-ry_randolph@ 123456meei.harvard.edu
                [5 ]Harvard Medical School Boston, Harvard Medical School, Boston, MA 02115, USA
                Author notes
                [* ]Correspondence: etoraih@ 123456tulane.edu (E.A.T.); ekandil@ 123456tulane.edu (E.K.)
                Author information
                https://orcid.org/0000-0001-8534-6630
                https://orcid.org/0000-0001-9267-3787
                https://orcid.org/0000-0001-5373-9181
                Article
                cancers-13-01402
                10.3390/cancers13061402
                8003482
                33808717
                a8772ac9-3c11-48e2-8195-36491771f896
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 February 2021
                : 11 March 2021
                Categories
                Article

                thyroid cancer,sptc,breast cancer,systematic review
                thyroid cancer, sptc, breast cancer, systematic review

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