XPD polymorphism and risk of subsequent cancer in individuals with nonmelanoma skin cancer.
BACKGROUND
Individuals with nonmelanoma skin cancer (NMSC) are at increased risk of developing subsequent cancers. Genetic predisposition to reduced DNA repair capacity may be an underlying susceptibility factor explaining the excess risk of malignancies. To test this hypothesis, a cohort study was conducted to examine the association between XPD Lys751Gln polymorphism and risk of a second primary cancer in individuals with NMSC.


METHODS
A subgroup of 481 individuals with a history of NMSC who participated in the CLUE II community-based cohort was followed for the development of a second primary cancer. Blood specimens donated in 1989 were genotyped for the XPD Lys751Gln polymorphism using the 5' nuclease assay. Cox proportional regression with delayed entry was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (95% CI) for risk of developing a second primary cancer according to XPD genotype. All statistical tests were two sided.


RESULTS
Eighty individuals developed a second primary cancer. The most frequent occurring cancers were of the prostate (18%), lung (15%), and breast (15%). Persons with at least one Gln allele had an increased risk of a second primary cancer compared with the reference Lys/Lys genotype (adjusted IRR 2.22, 95% CI 1.30-3.76). When the reference category was limited to never smokers with the Lys/Lys genotype, the risk of developing a second primary cancer associated with having at least one Gln allele was increased >3-fold in both never smokers (IRR 3.93, 95% CI 1.36-11.36) and ever smokers (IRR 6.14, 95% CI 2.17-17.37).


CONCLUSIONS
These findings suggest that individuals with NMSC who have the variant XPD Gln allele are at increased risk of developing a second primary cancer.
Department of Clinical Cancer Prevention, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Abenaa M
AM
Brewster
Anthony J
AJ
Alberg
Paul T
PT
Strickland
Sandy C
SC
Hoffman
Kathy
K
Helzlsouer
D017677:Age Distribution; D000368:Aged; D000483:Alleles; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D015331:Cohort Studies; D016001:Confidence Intervals; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D017678:Sex Distribution; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human