ELECTRONIC LETTER
Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450 (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in families with the naevoid basal cell carcinoma syndrome
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
Correspondence to:
Correspondence to:
Dr Xiaohong (Rose) Yang
Genetic Epidemiology Branch, DCEG, NCI, 6120 Executive Blvd., Rm 7014, Bethesda, MD 20852, USA; royang{at}mail.nih.gov
Background: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant multisystem disorder with variable expression. NBCCS patients have variable susceptibility to development of basal cell carcinoma (BCC). Previous studies have shown that polymorphisms of some metabolic genes encoding the cytochrome p450 (CYP) and glutathione-S-transferase (GST) enzymes influenced the numbers of BCCs in sporadic BCC cases.
Objective: To determine whether allelic variants of these genes contribute to the variation in numbers of BCCs observed in NBCCS families.
Methods: Genotyping and analysis was carried out in 152 members (69 affected and 83 unaffected) of 13 families with NBCCS for seven polymorphisms in five metabolic genes including CYP1A1, CYP2D6, GSTM1, GSTP1, and GSTT1.
Results: GSTP1 Val105 and GSTP1 Val114 alleles were significantly associated with fewer BCC numbers (odds ratio (OR)105 = 0.55 (95% confidence interval, 0.35 to 0.88); OR114 = 0.20 (0.05 to 0.88)). The Val105 allele showed a dose dependent effect (ORIle/Val = 0.58 (0.34 to 0.88); ORVal/Val = 0.34 (0.14 to 0.78)). In addition, fewer jaw cysts were observed in carriers of the three p450 polymorphisms (CYP1A1m1, CYP1A1m2, and CYP2D6*4) (ORCYP1A1m1 = 0.27 (0.12 to 0.58); ORCYP1A1m2 = 0.25 (0.08 to 0.78); ORCYP2D6*4 = 0.33 (0.18 to 0.60)).
Conclusions: Genetic variants might contribute to the variation in numbers of BCCs and jaw cysts observed in NBCCS families.
Abbreviations: BCC, basal cell carcinoma; BPDE, benzo(a)pyrene diol epoxide; GEE, generalised estimating equations; GST, glutathione-S-transferase; NBCCS, naevoid basal cell carcinoma syndrome; PAH, polycyclic aromatic hydrocarbon
Keywords: glutathione-S-transferase; cytochrome p45; genetic polymorphism; naevoid basal cell carcinoma syndrome
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