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Importance of tumor location and histology in familial risk of upper gastrointestinal cancers: a nationwide cohort study

Authors Kharazmi E, Babaei M, Fallah M, Chen T, Sundquist K, Hemminki K

Received 14 March 2018

Accepted for publication 22 May 2018

Published 4 September 2018 Volume 2018:10 Pages 1169—1179

DOI https://doi.org/10.2147/CLEP.S168152

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Professor Henrik Toft Sørensen


Elham Kharazmi,1,2* Masoud Babaei,1,3* Mahdi Fallah,2 Tianhui Chen,1,4 Kristina Sundquist,5,6 Kari Hemminki1,5

1Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 2Division of Preventive Oncology, National Center for Tumor Diseases, Heidelberg, Germany; 3Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Group of Molecular Epidemiology and Cancer Precision Prevention, Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences (ZJAMS), Hangzhou, People’s Republic of China; 5Center for Primary Health Care Research, Lund University, Malmö, Sweden; 6Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA

*These authors contributed equally to this work

Background: Familial clustering of upper gastrointestinal (UGI) cancers and the significance of family history has been addressed previously. We aimed to elucidate the familial risk based on the specified tumor location and histology.
Method: In the Swedish Family-Cancer Database, we determined the familial risk of UGI cancer patients diagnosed (1958–2015) with esophageal and gastric cancer by tumor location using standardized incidence ratios (SIRs).
Results: Risk of esophageal cancer in first-degree relatives (FDRs) of patients with esophageal cancer increased 2.4-fold (SIR 95% CI 2.0–2.8), whereas risk of esophageal cancer in cases with family history of cancer in the middle third of the esophagus increased 3.4-fold (SIR 95% CI 2.1–5.1). Risk of gastric cancer in FDRs increased 1.6-fold (SIR 95% CI 1.5–1.7), occurrence of concordant subsite gastric cancer in the antrum, body, and cardia was 5.5-fold (SIR 95% CI 2.4–11), 4.6-fold (SIR 95% CI 2.6–7.4), and 1.7-fold (SIR 95% CI 1.1–2.5), respectively. Familial risk of concordant histological subtype in esophageal cancer was 4.1-fold for squamous cell carcinoma (SIR 95% CI 3.2–5.2) and 3.6-fold for adenocarcinoma (SIR 95% CI 2.5–5.1). The risk of concordant gastric adenocarcinoma was 1.6-fold for one affected FDR (SIR 95% CI 1.5–1.7), 6.1-fold for two FDRs (SIR 95% CI 4.4–8.4), and 8.6-fold among twins (SIR 95% CI 2.3–22).
Conclusion: Family history of cancer in the lower third of the esophagus and stomach cancer in specific locations such as the antrum, body, and cardia can be considered as important predictive evidence for cancer in the same location in relatives. Our findings might guide endoscopy-based surveillance by introducing subgroups of populations with a higher risk for UGI cancer with particular attention to concordance of location of lesions, which could be a reasonable strategy for early detection, and thus help save more lives.

Keywords: familial risk, gastric cancer, stomach cancer, esophageal cancer, anatomic location, histology

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