Genetic variants in<i>MGMT</i>and risk of lung cancer in Southeastern Chinese: a haplotype-based analysis

Hu, Zhibin; Wang, Haifeng; Shao, Minhua; Jin, Guangfu; Sun, Weiwei; Wang, Yi; Liu, Hongliang; Wang, Ying; Ma, Hongxia; Qian, Ji; Jin, Li; Wei, Qingyi; Lu, Daru; Huang, Wei; Shen, Hongbing

doi:10.1002/humu.20462

Cited by 45 publications

(58 citation statements)

References 37 publications

(46 reference statements)

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“…The controls had no history of cancer and were frequency matched to each set of cancer patients on age (F 5 y), sex, and residential area (urban or countryside). The most parts of these case-control sets have been also published previously (28,29). The distributions of selected characteristics by case-control status are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Functional Genetic Variations in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Multiple Types of Cancer

Sun¹,

Zhou²,

Yang³

et al. 2008

Cancer Research

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Antitumor T lymphocytes play a pivotal role in immunosurveillance of malignancy. The CTL antigen 4 (CTLA-4) is a vital negative regulator of T-cell activation and proliferation. This study examined whether genetic polymorphisms in CTLA-4 are associated with cancer susceptibility. A two-stage investigation using haplotype-tagging single nucleotide polymorphism approach and multiple independent case-control analyses was performed to assess the association between CTLA-4 genotypes and cancer risk. Functional relevance of the polymorphisms was examined by biochemical assays. We found that the 49G>A polymorphism in the CTLA-4 leading sequence causing 17 Ala to 17 Thr amino acid substitution is associated with increased susceptibility to multiple cancers, including lung, breast, esophagus, and gastric cardia cancers. Genotyping in 5,832 individuals with cancer and 5,831 control subjects in northern and southern Chinese populations showed that the CTLA-4 49AA genotype had an odds ratio of 1.72 (95% confidence interval, 1.50À2.10; P = 3.4 Â 10 À7 ) for developing cancer compared with the 49GG genotype. Biochemical analyses showed that CTLA-4À 17 Thr had higher capability to bind B7.1 and stronger inhibitory effect on T-cell activation compared with CTLA-4À 17 Ala. T cells carrying the 49AA genotype had significantly lower activation and proliferation rates compared with T cells carrying the 49GG genotype upon stimulation. These results are consistent with our hypothesis and indicate that genetic polymorphisms influencing T-cell activation modify cancer susceptibility.

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Section: Methodsmentioning

confidence: 99%

Functional Genetic Variations in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Multiple Types of Cancer

Sun¹,

Zhou²,

Yang³

et al. 2008

Cancer Research

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201

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“…Quality control was performed as described previously in association with studies in lung cancer. 28 …”

Section: Genotype Assaymentioning

confidence: 99%

Genetic susceptibility of lung cancer associated with common variants in the 3′ untranslated regions of the adenosine triphosphate‐binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export

Wang

Jin

Wang

et al. 2009

Cancer

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Although Parkinson's disease (PD) is traditionally considered a motor output disorder, recent evidence suggests that people with PD may have sensory and perceptual impairments that may underlie movement impairments. Yet there has not been any direct testing of perceptual judgments, especially when manipulating the sensory feedback on which these judgments are made. The present study investigated how perception might be influenced by sensory feedback to contribute to height estimations and obstacle stepping in PD relative to healthy age‐matched control participants. Perceptual judgment accuracy was evaluated by judging 3 typically encountered obstacle heights in 2 sensory feedback conditions: (1) vision of foot available and (2) without vision of foot (reliance on proprioceptive feedback to estimate height). Then participants proceeded to walk and step over the obstacle. Fifteen individuals with PD and 15 healthy control participants completed the task. As seen with toe elevation, toe elevation variability, and toe error measures, individuals with PD overestimated the obstacle height and were significantly more variable when relying solely on proprioception (in contrast to when vision was available) compared with healthy controls, although no differences between groups in obstacle crossing were found. These results support the notion that sensory deficits may contribute to inaccuracy of perceptual judgment and has the potential to contribute to gait behaviors such as tripping and falling, especially when vision is not available. Future studies should carefully consider the impact of sensory and perceptual deficits that might contribute to movement planning problems and consequentially movement impairments. © 2011 Movement Disorder Society

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“…The study population and subject characteristics were described elsewhere (17). In brief, this hospital-based case-control study included 500 histopathologically confirmed incident lung cancer patients and 517 cancer-free controls, frequency-matched to the cases on age, sex, and residential areas.…”

Section: Methodsmentioning

confidence: 99%

Tagging Single Nucleotide Polymorphisms in Phosphoinositide-3-Kinase–Related Protein Kinase Genes Involved in DNA Damage “Checkpoints” and Lung Cancer Susceptibility

Liu

Wang

et al. 2008

Clinical Cancer Research

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Purpose: DNA damage checkpoints are initiated by its sensor proteins of the phosphoinositide-3-kinase^related protein kinase family, including ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3-related, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We hypothesized that polymorphisms in these genes may alter the regulation of DNA repair and the risk of lung cancer. Experimental Design: We genotyped 12 tagging single nucleotide polymorphisms (tSNP) in these three phosphoinositide-3-kinase^related protein kinase genes in 500 incident lung cancer cases and 517 controls in a Chinese population by using the Illumina SNP genotyping BeadLab platform. Results: Single locus analyses revealed that some of the heterozygotes or variant homozygotes of DNA-PKcs tSNPs were associated with decreased risks of lung cancer compared with their wild-type homozygotes. In the combined analyses of two tSNPs (rs8178085 and rs12334811) with approaching dose-dependent effect on lung cancer predisposition, subjects carrying two to four risk genotypes were associated with a 43% decreased lung cancer risk compared with subjects carrying zero to one risk genotypes (adjusted odds ratio, 0.53; 95% confidence interval, 0.35-0.80). Moreover, the decreased risk associated with the combined genotypes of rs8178085 and rs12334811was slightly more pronounced in nonsmokers and in carriers with ataxia-telangiectasia mutated rs228591 variant allele or ataxia-telangiectasia and Rad3-related rs6782400 wild-type homozygous genotype. Conclusion:These results indicate, for the first time, that tSNPs in DNA-PKcs may play a protective role in lung cancer development.Maintenance of genome stability is essential for avoiding the passage to neoplasia. DNA lesions that are not properly repaired before cell division can be mutagenic, resulting in mutations and the formation of a precancerous cell (1, 2).A wealth of information has been accumulated on DNA repair mechanisms over the past 50 years. Genetic defects disturbing these mechanisms can cause inherited syndromes that are characterized by hypersensitivity to specific DNA-damaging agents and predisposition to cancer (3). Although the repair of different types of DNA lesion relies on different sets of proteins, the various forms of DNA damage nevertheless trigger common response signals, such as DNA damage ''checkpoints'' (4, 5).Before detecting a specific type of DNA lesions, the cell must sense very low levels of DNA damage in the genome. The rapidity and potency of this DNA damage response demand very sensitive signal transduction cascades, initiated by the sensor proteins of the phosphoinositide-3-kinaserelated protein kinase (PIKK) family, including ataxiatelangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), and DNA-dependent protein kinase catalytic subunit refs. 4,6). ATM and DNA-PKcs respond mainly to DNA double-strand breaks, whereas ATR is activated by ssDNA and stalled DNA replication forks (7). Recently, Falck et al. (8) identified related, c...

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Genetic variants inMGMTand risk of lung cancer in Southeastern Chinese: a haplotype-based analysis

Cited by 45 publications

References 37 publications

Functional Genetic Variations in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Multiple Types of Cancer

Functional Genetic Variations in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Multiple Types of Cancer

Genetic susceptibility of lung cancer associated with common variants in the 3′ untranslated regions of the adenosine triphosphate‐binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export

Tagging Single Nucleotide Polymorphisms in Phosphoinositide-3-Kinase–Related Protein Kinase Genes Involved in DNA Damage “Checkpoints” and Lung Cancer Susceptibility

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