Carcinogenesis, Vol 19, 93-98, Copyright © 1998 by Oxford University Press
X Wu, TC Hsu, S Cao, JJ Lee, CI Amos and MR Spitz
The poly(ADP-ribose)polymerase (PADPRP) gene has been implicated in
carcinogenesis through its role in DNA repair, replication and
recombination. A two-allele polymorphism in the chromosome 13 PADPRP
pseudogene has been studied in several racial groups. It has been suggested
that the B allele, which results from a 193-bp deletion in the gene,
predisposes to myeloma in Blacks. We assessed the association between
chromosome 13 PADPRP pseudogene genotype, mutagen sensitivity (a marker
reflecting host DNA repair capability), cigarette smoking, and lung cancer
risk in a minority lung cancer case-control study. The chromosome 13 PADPRP
pseudogene polymorphism was detected by polymerase chain reaction-based
analysis. Mutagen sensitivity was measured by an in vitro assay that
quantified bleomycin-induced chromatid breaks in peripheral blood
lymphocyte cultures. We examined 121 cases (80 African- Americans and 41
Mexican-Americans) with previously untreated lung cancer and 171 matched
controls. Our results suggested that the distribution of the PADPRP
pseudogene genotype frequencies was significantly different among
African-American and Mexican-American controls (P < 0.001). The
susceptibility genotype (i.e. at least one B allele) was found in 82.5% of
African-American cases, 79.4% of African- American controls, 53.7% of
Mexican-American cases, and 32.4% of Mexican-American controls. The odds
ratios (OR) and 95% confidence intervals for the PADPRP susceptibility
genotypes were 2.3 (95% CI = 0.7-8.0) and 3.2 (95% CI = 1.0-10.3) for
African-Americans and Mexican- Americans respectively, after adjustment by
age, sex, pack-years and mutagen sensitivity. Patients with the
susceptibility genotype appeared to have more mutagen-induced breaks than
did patients with the other genotype. Only adenocarcinoma was significantly
associated with the PADPRP susceptibility genotype (OR = 3.8). Mutagen
sensitivity (> or = 1 break/cell) was significantly associated with lung
cancer risk for both ethnic groups with increased ORs of above three-fold.
On stratified analysis, synergistic interactions were noted for the PADPRP
susceptibility genotype, mutagen sensitivity and smoking status. In
Mexican-Americans, the ORs for PADPRP susceptibility genotype, mutagen
sensitivity and both risk factors combined were 1.3, 2.7 and 17.1
respectively. The combined OR for the PADPRP susceptibility genotype and
smoking status was 15.6. Therefore, this polymorphism appears to be
associated with lung cancer risk. However, it is likely that no single
genotype is sufficiently predictive of risk and that a panel of
susceptibility markers is needed to define the high-risk subgroup.
ARTICLES
Deletion in poly(ADP-ribose)polymerase pseudogene and lung cancer risk
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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