Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China.
Lung cancer rates in Xuan Wei County are among the highest in China and have been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons (PAHs). The NBS1 gene product participates in DNA double-strand break repair and DNA damage-induced checkpoint activation, which are critical for maintaining genomic integrity. The p53 tumor suppressor gene is known to play key roles both in the maintenance of genomic stability in mammalian cells and in DNA damage surveillance. We examined the association between two common NBS1 polymorphisms (Leu34Leu, Gln185Glu) and lung cancer risk in a population-based case-control study in Xuan Wei, China. Individuals homozygous for the NBS1 34Leu or NBS1 185Glu variants were found to have an increased risk of lung cancer (odds ratio [OR] 2.15, 95% confidence interval [CI]: 0.91-5.10 and OR 2.53, 95% CI: 1.05-6.08, respectively). A haplotype containing the variant alleles from both NBS1 SNPs was associated with increased risk of lung cancer compared with the most common haplotype. Further, the associations were particularly pronounced among cases with over expression of p53 protein. These results suggest that NBS1 could be important in the pathogenesis of lung cancer in this population. However, additional studies in other populations with substantial environmental exposures to PAHs are needed to confirm our findings.
Lan
Qing
Q
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, MSC 7240, 6120 Executive Blvd., EPS 8109, Bethesda, MD 20892-7240, USA. qingl@mail.nih.gov
Shen
Min
M
Berndt
Sonja I
SI
Bonner
Matthew R
MR
He
Xingzhou
X
Yeager
Meredith
M
Welch
Robert
R
Keohavong
Phouthone
P
Donahue
Mark
M
Hainaut
Pierre
P
Chanock
Stephen
S
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D003031:Coal / Q000009:adverse effects*; D004249:DNA Damage; D004260:DNA Repair; D004781:Environmental Exposure; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects; D011110:Polymorphism, Genetic; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics*
D018797:Cell Cycle Proteins; D003031:Coal; C112156:NBN protein, human; D009687:Nuclear Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53