Genetic susceptibility to occupational exposures

Dc, Christiani; Aj, Mehta; Yu, Chenxu

doi:10.1136/oem.2007.033977

Cited by 60 publications

(35 citation statements)

References 54 publications

(60 reference statements)

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“…Cancer is a typical complex disorder to which a yet unknown number of genes contribute through interactions among each other and the environment (Velculescu, 2008;Christiani et al, 2008). Specific antigens of the HLA system are known to be associated with many solid tumors (Schirle, 2002;Seliger et al, 2003;Cabrera et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Novel association analysis between HLA-DQB1 polymorphisms and rectal cancer based on a cross-validation design

Tong¹,

Wen²,

Liu³

2013

Genet. Mol. Res.

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ABSTRACT.A new study design based on cross-validation of the age at the onset of rectal cancer and the differences between the frequency distributions of relevant genes in 2 groups was developed for identification of disease-related HLA. Patients with rectal cancer were recruited and their age at the time of the first surgery was recorded. The genetic variants of HLA-DQB1 were genotyped using an HLA-DQB1 PCR-SSP typing kit. Allele frequencies were compared with control population. The mean age of patients with and without the alleles was compared. The frequency values of HLA-DQB1*02 were 12.3% higher in the cancer group than in the control population (P < 0.05). The median ages of the subjects with and without HLA-DQB1*02 were 54.0 and 61.0 years, respectively, with significant difference observed between the ages for these groups (P < 0.05). The median ages of the subjects with and without HLA-DQB1*03 were 62.0 and 58.0 years, respectively, and a significant difference was observed. The crossvalidation of the 2 above mentioned analytical results showed that a Cross-validation design for identification of cancer-related genes statistically significant difference was noted for HLA-DQB1*02 (P < 0.05), whereas no such statistically significant difference was observed for HLA-DQB1*03. HLA-DQB1*02 allele was related to cancer susceptibility. The new analysis method may be an efficient and reliable approach for the identification of disease-related HLA.

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Section: Discussionmentioning

confidence: 99%

Novel association analysis between HLA-DQB1 polymorphisms and rectal cancer based on a cross-validation design

Tong¹,

Wen²,

Liu³

2013

Genet. Mol. Res.

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“…Genetic factors can contribute to the variable responses of workers to occupational hazards-particularly chemical hazards and some biological and physical agents ( Table 1) (3,7,10,31,35). Workplace exposures to chemical and physical agents are increasingly being controlled to lower concentrations, but workers with susceptible genetic profiles may still be at higher than average risk.…”

Section: Role Of Genetics In the Variability Of Response To Occupatiomentioning

confidence: 99%

“…Workplace exposures to chemical and physical agents are increasingly being controlled to lower concentrations, but workers with susceptible genetic profiles may still be at higher than average risk. A growing body of published evidence has shown that genetic polymorphisms are indicators of varying risk for occupational disease in exposed workers (2,5,7,16,22,31,34). Advances in genetic technologies have been useful in studies of occupational disease and chemical exposures, especially in understanding mechanisms and modes of action.…”

Section: Role Of Genetics In the Variability Of Response To Occupatiomentioning

confidence: 99%

Genetic Susceptibility and the Setting of Occupational Health Standards

Schulte

Howard

2011

Annu. Rev. Public Health

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As more is learned about genetic susceptibility to occupational and environmental hazards, there will be increasing pressure to use genetic susceptibility information in setting occupational health standards. Historically, this has not been done, but a growing body of research assesses inherited genetic factors as modifiers of the effects of hazardous exposures. Additionally, acquired genetic and epigenetic characteristics could also be used in standard setting. However, for both inherited and acquired genetic characteristics, many scientific, ethical, legal, and social issues could arise. Investigators need to examine the potential role and implications of using genetic information in standard setting. In this review, we focus primarily on inherited genetic factors and their role in occupational health standard setting.

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“…Cancer is typically a complex disorder to which, until now, an unknown number of genes contribute by interacting with each other and the environment (3,4). The identities of these genes have remained elusive in spite of the rapid pace of development of molecular technology and the increase in genome sequence information.…”

Section: Introductionmentioning

confidence: 99%

Efficient association analysis between colorectal cancer and allelic polymorphisms of HLA-DQB1 by comparison of age of onset

2011

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Abstract. Common methods for identifying cancer-related genes are solely based on differences between gene frequencies in the disease and control groups, and do not take into account the age of onset in the gene carriers. In the present investigation, we developed a new study design based on the age of onset of cancer for the identification of colorectal cancerrelated genes. The samples from patients with colorectal cancer were typed using an HLA-DQB1 polymerase chain reaction using a sequence-specific primers (PCR-SSP) typing kit. The mean age of subjects with and without the alleles was calculated. The mean age of subjects with the HLA-DQB1*02 allele was significantly less than that of subjects without this allele (p<0.05). We found that the HLA-DQB1*02 allele was associated with colorectal cancer susceptibility. This new method of analysis may therefore be an efficient and reliable approach for the identification of cancer-causing genes. IntroductionGenetic linkage analysis has been highly successful in mapping the genes responsible for Mendelian diseases. During the past decade, attempts have been made to extend this approach to multifactorial disorders and other health-related traits. However, since complex diseases, including colorectal cancer, are characterized by the modest contributions of each susceptibility gene, identification of strong and replicable linkages has proven to be difficult (1,2). In this regard, the results of our linkage studies on human leukocyte antigen (HLA) allele polymorphisms and cancers have also been discouraging owing to inconsistent findings and weak linkage signals; however, these studies have indicated that genetic factors may affect the early onset of cancer. Therefore, we developed a new study design based on the age of onset of cancer.Cancer is typically a complex disorder to which, until now, an unknown number of genes contribute by interacting with each other and the environment (3,4). The identities of these genes have remained elusive in spite of the rapid pace of development of molecular technology and the increase in genome sequence information. This scenario may be partly attributed to by the absence of methods for high-efficacy analysis of genetic information. Single nucleotide polymorphisms (SNPs) are currently popular allelic markers (5,6); however, their value is largely qualitative. They may not be satisfactory indicators of complex diseases owing to their low quantitative efficacy. Our new study design uses the age of onset of cancer as an indicative factor that may provide a quantitative rather than a qualitative estimate (by assessing allele frequency at the locus). The efficacy of analysis may be improved since a quantitative measure is more statistically robust than a qualitative one.The HLA complex genes are located on the short arm of chromosome 6 and are the most polymorphic loci within the human genome. The primary function of HLA is to stimulate the immune system to identify infectious pathogens and eliminate them. The status of HLA alleles is impor...

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Genetic susceptibility to occupational exposures

Cited by 60 publications

References 54 publications

Novel association analysis between HLA-DQB1 polymorphisms and rectal cancer based on a cross-validation design

Novel association analysis between HLA-DQB1 polymorphisms and rectal cancer based on a cross-validation design

Genetic Susceptibility and the Setting of Occupational Health Standards

Efficient association analysis between colorectal cancer and allelic polymorphisms of HLA-DQB1 by comparison of age of onset

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