Scholarlink

Background <p>We investigated whether markers, genes or terms of the <i>Human Phenotype Ontology</i> associated with genetic or rare diseases (GARDs) that affect airway or lung function are associated with lung cancer.</p> Methods <p>Genes of interest were extracted from <i>GARD (Genetic and Rare Diseases Information Center)</i>, <i>OMIM (</i>Online Mendelian Inheritance in Man®), <i>ORPHANET</i> and Monarch Initiative. Individual SNP, gene level and gene-set analyses were performed for 52,207 SNPs, 1677 genes or for 620 terms of the <i>Human Phenotype Ontology</i>. The analysis included 14,068 lung cancer cases and 12,390 cancer-free control subjects of European descent from the International Lung Cancer Consortium ILCCO.</p> Results <p>The marker rs56113850 (OR=0.893, 95%CI: 0.862-0.924) was associated with lung cancer (<i>p</i>=1.2x10<sup>-10</sup>). This marker is located in CYP2A6 as well as in an enhancer region of <i>LTBP4</i>, which is associated with cutis laxa. A suggestive significant association was observed for two markers associated with the <i>DMD</i> gene, which is linked to Duchenne muscular dystrophy. The gene sets "Abnormal circulating adrenocorticotropin concentration" and "Central nervous system neoplasm" were found to be significantly enriched with GARD genes, and can therefore be considered to be associated with lung cancer.</p> Conclusions <p>Genes associated with genetic and rare lung diseases do not generally appear to carry risk factors for lung cancer. However, genes associated with the hypothalamic-pituitary-adrenal axis show some, but rather weak or complex, associations with lung cancer. Tests at the gene level provide extremely inhomogeneous results, even when applied to the same data.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genes associated with genetic and rare lung diseases and the risk of lung cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月1日

查看全文
  • Albert Rosenberger,
  • Heike Bickeböller,
  • David C. Christiani,
  • Neil E. Caporaso,
  • Geoffrey Liu,
  • Stig E. Bojesen,
  • Loic Le Marchand,
  • Demetrios Albanes,
  • Melinda C. Aldrich,
  • Adonina Tardon,
  • Guillermo Fernández‐Tardón,
  • Gad Rennert,
  • John K. Field,
  • Michael P. A. Davies,
  • Lambertus A. Kiemeney,
  • Philip Lazarus,
  • Shanbeh Zienolddiny,
  • Stephen Lam,
  • Matthew B. Schabath,
  • Angeline S. Andrew,
  • Susanne M. Arnold,
  • Gary E. Goodman,
  • Jennifer A. Doherty,
  • Fiona Taylor,
  • Angela Cox,
  • Penella J. Woll,
  • Angela Risch,
  • Mikael Johansson,
  • Paul Brennan,
  • Maria Teresa Landi,
  • Sanjay S. Shete,
  • Rayjean J. Hung,
  • Christopher I. Amos

摘要

Background

We investigated whether markers, genes or terms of the Human Phenotype Ontology associated with genetic or rare diseases (GARDs) that affect airway or lung function are associated with lung cancer.

Methods

Genes of interest were extracted from GARD (Genetic and Rare Diseases Information Center), OMIM (Online Mendelian Inheritance in Man®), ORPHANET and Monarch Initiative. Individual SNP, gene level and gene-set analyses were performed for 52,207 SNPs, 1677 genes or for 620 terms of the Human Phenotype Ontology. The analysis included 14,068 lung cancer cases and 12,390 cancer-free control subjects of European descent from the International Lung Cancer Consortium ILCCO.

Results

The marker rs56113850 (OR=0.893, 95%CI: 0.862-0.924) was associated with lung cancer (p=1.2x10-10). This marker is located in CYP2A6 as well as in an enhancer region of LTBP4, which is associated with cutis laxa. A suggestive significant association was observed for two markers associated with the DMD gene, which is linked to Duchenne muscular dystrophy. The gene sets "Abnormal circulating adrenocorticotropin concentration" and "Central nervous system neoplasm" were found to be significantly enriched with GARD genes, and can therefore be considered to be associated with lung cancer.

Conclusions

Genes associated with genetic and rare lung diseases do not generally appear to carry risk factors for lung cancer. However, genes associated with the hypothalamic-pituitary-adrenal axis show some, but rather weak or complex, associations with lung cancer. Tests at the gene level provide extremely inhomogeneous results, even when applied to the same data.