The polymorphisms and haplotypes of WWOX gene are associated with the risk of lung cancer in southern and eastern chinese populations

Huang, Dongsheng; Qiu, Fuman; Yang, Lei; Li, Yinyan; Cheng, Minquan; Wang, Hui; Ma, Guanpei; Wang, Yunnan; Hu, Min; Ji, Weidong; Zhou, Yifeng

doi:10.1002/mc.21934

Cited by 17 publications

(25 citation statements)

References 41 publications

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“…Several studies have suggested that WWOX polymorphic variants are consistently associated with more aggressive phenotypes and poor outcomes in numerous malignant diseases, including esophageal squamous cell carcinoma, thyroid carcinoma, pancreatic cancer, and lung cancer [36, 40–42]. In the current study, we evaluated variations in the WWOX gene and the clinicopathological development of HCC across 2 independent individuals.…”

Section: Discussionmentioning

confidence: 99%

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Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

et al. 2017

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BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk.Methodology/Principal findingsFive single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion.ConclusionsIn conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.

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Section: Discussionmentioning

confidence: 99%

“…In this study, the selection of 5 well-characterized common polymorphisms from WWOX gene is based on their wide associations with the development of cancer [35, 36]. We included rs11545028 in the 5’UTR region.…”

Section: Methodsmentioning

confidence: 99%

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

et al. 2017

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“…Functional annotations from the ENCODE data indicate that rs11545028 is located in the region of an open chromatin, which probably corresponds to the promoters and CpG islands of WWOX . Several studies have documented the importance of transcriptional regulation between WWOX polymorphisms and cancer risk [23, 33]. Moreover, the common modifications of epigenetic changes in chromatin include DNA methylation, which has been considered a crucial mechanism underlying the inactivation of tumor suppressor genes as well as the loss of heterozygosity and mutation.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the selection of 5 well-characterized common polymorphisms from WWOX gene is based on their wide associations with the development of cancer (Table 1, Figure 1A) [23–26, 33]. We included rs11545028 in the 5′UTR region.…”

Section: Methodsmentioning

confidence: 99%

Functional genetic variant in the Kozak sequence of WW domain-containing oxidoreductase (WWOX) gene is associated with oral cancer risk

Cheng

Liu

et al. 2016

Oncotarget

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In Taiwan, oral cancer is the fourth leading cancer in males and is associated with exposure to environmental carcinogens. WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the development of various cancers. We hypothesized that genetic variants of WWOX influence the susceptibility to oral cancer. Five polymorphisms of WWOX gene from 761 male patients with oral cancer and 1199 male cancer-free individuals were genotyped. We observed that individuals carrying the polymorphic allele of WWOX rs11545028 are more susceptible to oral cancer. Furthermore, patients with advanced-stage oral cancer were associated with a higher frequency of WWOX rs11545028 polymorphisms with the variant genotype TT than did patients with the wild-type gene. An additional integrated in silico analysis confirmed that rs11545028 affects WWOX expression, which significantly correlates with tumor expression and subsequently with tumor development and aggressiveness. In conclusion, genetic variants of WWOX contribute to the occurrence of oral cancer, and the findings regarding these biomarkers provided a prediction model for risk assessment.

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“…Th e variants in WWOX also aff ect susceptibility of lung cancer (19). As an oxidoreductase, WWOX contains a short-chain dehydrogenase/reductase domain and participates in pathways involving oxidative stress (20), and thus may play a role in development of COPD, because oxidative stress is a key etiological mechanism of COPD (21).…”

mentioning

confidence: 99%

The Functional Copy Number Variation-67048 inWWOXContributes to Increased Risk of COPD in Southern and Eastern Chinese

Yang

Qiu

Fang

et al. 2014

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Recent studies have recognized the genetic variants in the WW domain-containing oxidoreductase (WWOX) gene as genetic determinants of lung function, reflecting that the WWOX gene may be a susceptible factor of chronic obstructive pulmonary disease (COPD), which characters as poor lung function. We have previously showed that the copy number variation-67048 (CNV-67048) of WWOX was associated with lung cancer risk. Here, we hypothesized that the CNV-67048 affects COPD susceptibility. Based on a two-stage case-control study with a total of 1791 COPD patients and 1940 controls of southern and eastern Chinese, we found that the loss genotypes (0-copy and 1-copy) of CNV-67048 harbored a significantly increased risk of COPD, with an odds ratio (OR) as 1.29 (1.11-1.49) when compared with the common 2-copy genotype. The pre-forced expiratory volume in one second (pre-FEV1) to pre-forced vital capacity (pre-FVC) of carriers with loss genotypes (0.729 ± 0.130) was significantly lower than carriers with 2-copy genotype (0.747 ± 0.124; p = 7.93 × 10(-5)). However, no significant difference was observed on pre-FEV1, pre-FVC and the annual decline of pre-FEV1 between the loss genotypes and 2-copy genotype carriers. Our data suggest that the loss genotypes of CNV-67048 in WWOX predispose their carriers to COPD, which might be a genetic biomarker to predict risk of COPD in Chinese.

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The polymorphisms and haplotypes of WWOX gene are associated with the risk of lung cancer in southern and eastern chinese populations

Cited by 17 publications

References 41 publications

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

Functional genetic variant in the Kozak sequence of WW domain-containing oxidoreductase (WWOX) gene is associated with oral cancer risk

The Functional Copy Number Variation-67048 inWWOXContributes to Increased Risk of COPD in Southern and Eastern Chinese

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