OP0253 AUTOANTIBODY STATUS IN DERMATOMYOSITIS AND POLYMYOSITIS PATIENTS DEFINES BOTH CANCER RISK AND SURVIVAL WITH ANA NEGATIVITY IN CASES WITH CONCOMITANT CANCER HAVING A WORSE SURVIVAL

Background:We previously reported that ANA-negative cases with systemic sclerosis (SSc) and concomitant cancer had a worse survival than ANA-positive cases with associated cancer possibly suggesting that humoral mediated autoimmunity conferred a survival advantage (1). Dermatomyositis (DM) and polymyositis (PM) are two immune-mediated myopathies associated with numerous autoantibodies.Objectives:The present large-scale, population-based study tested the hypothesis that humoral autoimmunity associated with cancer in solid/haematological malignancies impacted on DM/PM patient survival.Methods:Over 2000 cases with either DM or PM were recruited from the Clalit Health Service (CHS) chronic diseases registry, one of the largest healthcare maintenance Israeli organization, serving approximately half of the entire country’s population. Over 10000 matched controls were recruited. The data collected range from 2000 to 2018.Results:Altogether 12,278 subjects were recruited (2,085 cases, and 10,193 controls, 5,042 males, 41.1%, and 7,236 females, 58.9%). Among cases, 1,475 individuals (70.7%) were diagnosed with DM, whereas 610 (29.3%) with PM. Mean age was 47.81±22.51 years. 1,379 cases of cancers (11.2%) were diagnosed. At the univariate analysis and as expected, the rate of malignancies was significantly (p<0.0001) higher in DM/PM (n=361, 17.3%) with respect to controls (n=1,018, 10.0%).Concerning prognosis, ANA positivity in PM/DM was associated with a better prognosis for all cancers (OR 0.39 [95% 0.24-0.63], p=0.0001). For individual cancer types; thyroid cancer (OR 0.39 [95% 0.24-0.63], p=0.0001), gastric cancer (OR 0.40 [95% 0.25-0.64], p=0.0001), kidney cancer (OR 0.39 [95% 0.24-0. 62], p=0.0001), acute leukaemia (OR 0.40 [95% 0.25-0.65], p=0.0002), non-Hodgkin’s lymphoma (OR 0.39 [95% 0.25-0.63], p=0.0001), but not for myelodysplastic syndrome.The main cancers linked to PM/DM were thyroid cancer (OR 3.17 [95%CI 2.27-4.43]), gastric cancer (OR 5.96 [95%CI 4.24-8.38]), kidney cancer (OR 3.83 [95%CI 1.02-14.31], p=0.0462), and myelodysplastic syndrome (OR 2.01 [95%CI 1.17-3.46], p=0.0111). Regarding gastric cancer, positivity for anti-RNP (OR 5.68 [95%CI 3.02 to 10.71], p<0.0001), anti-SSA (OR 21.99 [95%CI 11.21 to 43.14], p<0.0001), and anti-Jo1 (OR 12.23 [95%CI 7.12 to 21.01], p<0.0001) was associated with a higher risk of cancer development.Conclusion:ANA positivity is an independent predictor of favorable prognosis in PM/DM patients with cancer, possibly suggesting that cancer directed humoral autoimmunity may have some benefit. Therefore, humoral autoimmunity in SSc and PM/DM is a broad mechanism that confers a survival advantage and is relevant for disease understanding and elucidating optimal anti tumoural immunity in the current age of cancer immunotherapy.References:[1]Watad A, McGonagle D, Bragazzi NL, Tiosano S, Comaneshter D, Shoenfeld Y, Cohen AD, Amital H. Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival. Oncoimmunology. 2019 Mar 24;8(6):e1588084.Disclosure of Interests:Abdulla Watad: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Merav Lidar: None declared, Nicola Luigi Bragazzi: None declared, Doron Comanesther: None declared, Arnon Cohen: None declared, Howard Amital: None declared

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The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

BMC Medical Genomics ◽

10.1186/s12920-021-00965-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

OncoImmunology ◽

10.1080/2162402x.2019.1588084 ◽

2019 ◽

Vol 8 (6) ◽

pp. e1588084 ◽

Cited By ~ 7

Author(s):

Abdulla Watad ◽

Dennis McGonagle ◽

Nicola L. Bragazzi ◽

Shmuel Tiosano ◽

Doron Comaneshter ◽

...

Keyword(s):

Systemic Sclerosis ◽

Cancer Risk ◽

Autoantibody Status

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The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case-control studies

10.21203/rs.3.rs-454818/v1 ◽

2021 ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background: Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results: XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG+AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion: This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-105991 ◽

2019 ◽

Vol 56 (12) ◽

pp. 838-843 ◽

Cited By ~ 18

Author(s):

Rosa M Xicola ◽

Shuwei Li ◽

Nicolette Rodriguez ◽

Patrick Reinecke ◽

Rachid Karam ◽

...

Keyword(s):

Breast Cancer ◽

Gastric Cancer ◽

Cancer Risk ◽

Pathogenic Variant ◽

Age At Diagnosis ◽

Breast Cancers ◽

Cancer Risks ◽

Clinical Criteria ◽

Gastric Cancers ◽

Risk Of Cancer

BackgroundThe clinical phenotype of CDH1 pathogenic variant carriers has mostly been studied in families that fulfil criteria of hereditary diffuse gastric cancer (HDGC). We aimed at determining cancer phenotype and cancer risk estimation among families with CDH1 pathogenic variants not selected by HDGC clinical criteria.MethodsPatients were all consecutively identified CDH1 pathogenic variant carriers from a clinical laboratory tested with multigene panel testing and from an academic cancer genetics programme. Clinical and demographic features, cancer phenotypes and genotype–phenotype correlations were determined among CDH1 families. Age-specific cumulative cancer risks (penetrance) were calculated based on 38 families with available pedigrees.ResultsWithin the 113 CDH1 pathogenic variant probands and 476 relatives, 113 had gastric cancer, 177 breast cancer and 196 other cancers. Mean age at diagnosis was 47 for gastric and 54 for breast cancer. Forty-six per cent fulfilled criteria of HDGC. While 36% of families had both gastric and breast cancers, 36% had breast but no gastric cancers and 16% had gastric but not breast cancers. Cumulative risk of cancer by age 80 was 37.2% for gastric and 42.9% for breast cancer.ConclusionIn unselected CDH1 pathogenic variant carrier families, gastric cancer risks were lower and age at diagnosis higher than previously reported in families pre-selected for HDGC criteria. A substantial proportion of families did not present with any gastric cancers and their cancers were limited to breast. Thus, clinical criteria for CDH1 testing should be widened, including breast cancer families only, and a consideration for delayed prophylactic gastrectomy/surveillance should be evaluated.

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