Familial risks between Graves disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden

Thomsen, Hauke; Li, Xinjun; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Kari

doi:10.1016/j.jtauto.2020.100058

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…Disease associations with HT may shed further light on pathogenesis. A comprehensive study of over 25,000 offspring of HT patients has confirmed familial associations among 20 of 43 other autoimmune disorders, 6 of which (autoimmune haemolytic anaemia, chronic rheumatic heart disease, chronic glomerulonephritis, immune thrombocytopenic purpura, pemphigus and Takayasu disease) were not found in a similar cohort of Graves’ patients [ 44 ]. In addition modest spouse correlation was found within the overall familial risk, indicating some sharing of environmental risk factors, but the overwhelming risk was genetic and shared with other autoimmune disorders.…”

Section: Associations With Htmentioning

confidence: 99%

An update on the pathogenesis of Hashimoto’s thyroiditis

Weetman

2020

J Endocrinol Invest

142

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It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto’s thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT.

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Section: Associations With Htmentioning

confidence: 99%

An update on the pathogenesis of Hashimoto’s thyroiditis

Weetman

2020

J Endocrinol Invest

142

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“… 39 Thyroid autoimmune diseases are the most common type of autoimmune diseases in Sweden, accounting for over 10% of all such diseases. 40 Hashimoto disease/hypothyroidism is the most common thyroid autoimmune disease and it is associated with a high risk of HCC; 12 however, whether thyroid autoimmunity is a precursor of thyroid cancer is somewhat disputed. 41 , 42 Thus there may yet be other reasons; liver cancer is marginally increased in families of patients with non-medullary thyroid cancer but no associated genes have been identified.…”

Section: Discussionmentioning

confidence: 99%

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers

Zheng¹,

Sundquist²,

Sundquist³

et al. 2021

CLEP

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Background Second primary cancers (SPCs) are important clinically as they may negatively influence patient survival and they may tell about therapeutic side effects and general causes of cancer. Population-based literature concerning SPCs after hepatobiliary cancers is limited and here we assess risks of SPCs after hepatocellular cancer (HCC), and cancers of the gallbladder, bile ducts and ampulla of Vater. In reverse order, we consider the risk of hepatobiliary cancers as SPCs after any cancer. Methods We used standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancers associated with hepatobiliary cancers. Cancer diagnoses were obtained from the Swedish Cancer Registry from years 1990 through 2015. Results We identified 9997 primary HCCs, 1365 gallbladder cancers and 4721 bile duct cancers. After HCC, risks of four SPCs were increased: gallbladder (SIR = 4.38; 95% confidence interval 1.87–8.67), thyroid (4.13; 1.30–9.70), kidney (2.92; 1.66–4.47) and squamous cell skin (1.55; 1.02–2.26) cancers. In reverse order, HCC as SPC, in addition to the above cancers, associations included upper aerodigestive tract, esophageal, small intestinal and bladder cancers and non-Hodgkin lymphoma. For gallbladder and bile duct cancers, associations were found with small intestinal and pancreatic cancers. Conclusion The results suggested that HCC is associated with two types of SPC, one related to shared environmental risk factors, such as alcohol, exemplified by upper aerodigestive tract and esophageal cancer, and the other related to immune dysfunction, exemplified by squamous cell skin cancer. SPCs associated with gallbladder and bile duct cancers suggest predisposition to mutations in the mismatch repair gene MLH1.

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“…The study populations were younger than the present one and the familial risks tended to be higher than the current ones. In our recent analysis of thyroid AIDs, we showed that Graves disease and Hashimoto thyroiditis were associated with PA with SIRs of 1.94 and 1.74, respectively; the PA population was younger than the present one [ 23 ]. The present results and the older studies show familial risks between PA and such common AIDs which present as comorbidities in the same individuals and which probably indicate underlying genetic susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden

Thomsen

Sundquist

et al. 2021

Autoimmune Diseases

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Background. Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods. We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results. The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions. The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.

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Familial risks between Graves disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden

Cited by 27 publications

References 26 publications

An update on the pathogenesis of Hashimoto’s thyroiditis

An update on the pathogenesis of Hashimoto’s thyroiditis

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers

Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden

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