A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives.

IF 2 4区医学 Q3 ONCOLOGY Hereditary Cancer in Clinical Practice Pub Date : 2024-11-14 DOI:10.1186/s13053-024-00299-z

Johanna Samola Winnberg, Litika Vermani, Wen Liu, Veronika Soller, Jessada Thutkawkorapin, Mats Lindblad, Annika Lindblom

{"title":"A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives.","authors":"Johanna Samola Winnberg, Litika Vermani, Wen Liu, Veronika Soller, Jessada Thutkawkorapin, Mats Lindblad, Annika Lindblom","doi":"10.1186/s13053-024-00299-z","DOIUrl":null,"url":null,"abstract":"Background: A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who's relatives had prostate-, and/or gastric cancer.Methods: The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model. Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case-control study.Results: Candidate loci/genes on ten chromosomal regions were suggested with odds ratios between 1.71-3.62 and p-values < 5 × 10-8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of DNA from 122 colorectal cancer patients with gastric- and/or prostate cancer in their families was performed to search for candidate variants in the haplotype regions. The identified candidate variants were tested in a nested case-control study of similar colorectal cancer cases and controls. There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested.Conclusions: This study demonstrated a proof of principle strategy to identify risk variants found by GWAS, and identified ten candidate loci that could be associated with colorectal, gastric- and prostate cancer.","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"22 1","pages":"25"},"PeriodicalIF":2.0000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562479/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditary Cancer in Clinical Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13053-024-00299-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who's relatives had prostate-, and/or gastric cancer.

Methods: The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model. Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case-control study.

Results: Candidate loci/genes on ten chromosomal regions were suggested with odds ratios between 1.71-3.62 and p-values < 5 × 10-8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of DNA from 122 colorectal cancer patients with gastric- and/or prostate cancer in their families was performed to search for candidate variants in the haplotype regions. The identified candidate variants were tested in a nested case-control study of similar colorectal cancer cases and controls. There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested.

Conclusions: This study demonstrated a proof of principle strategy to identify risk variants found by GWAS, and identified ten candidate loci that could be associated with colorectal, gastric- and prostate cancer.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

瑞典结直肠癌患者与胃癌和前列腺癌亲属的全基因组关联研究。

背景：有研究表明，结直肠癌、胃癌和前列腺癌家族具有复杂的遗传性。因此，我们对亲属患有前列腺癌和/或胃癌的结直肠癌患者进行了全基因组关联研究（GWAS）：GWAS 分析包括来自瑞典的 685 例结直肠癌病例和 4780 例健康对照。利用逻辑回归模型进行了滑动窗口单倍型分析。之后，我们进行了测序，以找到候选变异，最后在巢式病例对照研究中进行检测：结果：我们发现了十个染色体区域的候选位点/基因，其几率比在 1.71-3.62 之间，P 值为结论：这项研究证明了一种识别 GWAS 发现的风险变异的原理性策略，并确定了可能与结直肠癌、胃癌和前列腺癌相关的 10 个候选位点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.