Genetic variants and risk of lung cancer in never smokers: a genome-wide association study

Li, Yafei; Sheu, Chau‐Chyun; Ye, Yuanqing; Andrade, Mariza de; Wang, Liang; Chang, Shen Chih; Aubry, Marie Christine; Aakre, Jeremiah A.; Allen, Mark S.; Chen, Feng; Cunningham, Julie M.; Deschamps, Claude; Jiang, Ruoxiang; Lin, Jie; Marks, Randolph S.; Pankratz, V. Shane; Li, Su; Li, Yan; Sun, Zhifu; Tang, Hui; Vasmatzis, George; Harris, Curtis C.; Spitz, Margaret R.; Jen, Jin; Wang, Renyi; Zhang, Zuo‐Feng; Christiani, David C.; Wu, Xifeng; Yang, Ping

doi:10.1016/s1470-2045(10)70042-5

Cited by 214 publications

(149 citation statements)

References 47 publications

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“…Thus, evidence is mounting for the GPC5 gene being a genuine susceptibility factor for MS. Recently, polymorphisms within this gene have been associated with sudden cardiac arrest 22 or lung cancer in non-smokers, 23 and variants in the adjacent GPC6 gene have also been associated with primary sclerosing cholangitis. 24 Both genes span around 3 Mb in 13q32, a chromosomal region where genomic amplification has been reported in different types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

et al. 2010

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“…Yu et al (40) reported that GPC5 is overexpressed in different lymphoma cell lines and they suggested that this gene is a likely target for 13q31-q32 amplification in lymphomas and other tumors. Conversely, a study on lung cancer demonstrated that GPC5 expression, as a result of a genetic variation, is significantly lower in adenocarcinoma compared to that in normal lung tissue (41). Another report by the same authors suggested that GPC5 regulates lung cancer development through a complex pathway network, although there is no direct evidence (20).…”

Section: A B C Dmentioning

confidence: 98%

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

Dinccelik-Aslan

Gümüş-Akay

Elhan

et al. 2015

Molecular and Clinical Oncology

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Abstract. Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer-related mortality. Previous studies revealed several genetic alterations specific to gastric cancer. In this study, we aimed to investigate the diagnostic and prognostic significance of the expression levels of the glypican 5 and glypican 6 genes (GPC5 and GPC6, respectively) in gastric cancer. For this purpose, GPC5 and GPC6 expression was quantitatively determined by quantitative polymerase chain reaction method in normal gastric mucosa and intestinal type gastric adenocarcinoma samples from 35 patients. The expression levels of GPC5 and GPC6 were compared between normal and tumor tissues. Additionally, the association of the expression levels in tumor tissues with several clinicopathological parameters was evaluated. Although GPC5 was not expressed in any of the samples, the expression of GPC6, which was detected in both groups, was found to be significantly higher in tumor tissues compared to that in normal samples (P=0.039). However, there was no statistically significant association between GPC6 expression and any of the clinicopathological parameters investigated (P>0.05). Our findings suggested that an increase in GPC6 expression levels may be implicated in gastric cancer development, but not in cancer progression.

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“…18,20 Analysis of subgroups of cases in GWAS data may therefore be valuable to identify further associations. Such analyses have been performed, 13,15,20,21 but this has generally been carried out without consideration of the relative power of these analyses, and the conditions under which such analyses are advantageous are not well understood. To resolve this, we seek to answer two questions.…”

Section: Introductionmentioning

confidence: 99%

Homogeneous case subgroups increase power in genetic association studies

2014

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Genome-wide association studies of clinically defined cases against controls have transformed our understanding of the genetic causes of many diseases. However, there are limitations to the simple clinical definitions used in these studies, and GWAS analyses are beginning to explore more refined phenotypes in subgroups of the existing data sets. These analyses are often performed ad hoc without considering the power requirements to justify such analyses. Here we derive expressions for the relative power of such subgroup analyses and determine the genotypic relative risks (GRRs) required to achieve equivalent power to a full analysis for relevant scenarios. We show that only modest increases in GRRs may be required to offset the reduction in power from analysing fewer cases, implying that analyses of more genetically homogenous case subgroups may have the potential to identify further associations. We find that, for lower genotypic relative risks in the full sample, subgroup analyses of more homogeneous cases have relatively more power than for higher index genotypic relative risks and that this effect is stronger for rare as opposed to common variants. As GWA studies are likely to have now identified the majority of SNPs with stronger effects, these results strongly advocate a renewed effort to identify phenotypically homogeneous disease groups, in which power to detect genetic variants with small effects will be greater. These results suggest that analysis of case subsets could be a powerful strategy to uncover some of the hidden heritability for common complex disorders, particularly in identifying rarer variants of modest effect.

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Genetic variants and risk of lung cancer in never smokers: a genome-wide association study

Cited by 214 publications

References 47 publications

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

Homogeneous case subgroups increase power in genetic association studies

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