title: Truncal site and detoxifying enzyme polymorphisms significantly reduce time to presentation of further primary cutaneous basal cell carcinoma.
abstract: Basal cell carcinoma (BCC) is the commonest cancer in Caucasians. Its incidence is rising and many patients develop multiple primary tumours at separate sites. Factors determining time between first primary tumour presentation and the next new primary lesion are unclear. We used Cox's proportional hazards model to study, in 856 Caucasians, the influence of tumour site, individual characteristics and polymorphism in glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) loci on time to next primary tumour presentation. More than one tumour at first presentation (P <0.0001, hazard ratio 2.72) and GSTT1 null (P = 0.028, hazard ratio 1.74) were associated with decreased time to next primary tumour presentation. Significant two-factor interactions, corrected for number of tumours at presentation, were identified between a truncal tumour at first presentation and each of male gender, GSTM1 null and CYP2D6 EM (P <0.003, hazard ratios 3.09-3.82). In each of these cases, all patients with the risk combination demonstrated further separate tumours within 5 years of first presentation. Thus, patients with a truncal tumour at first presentation, especially males and those presenting with more than one lesion have a significantly decreased time to presentation of further tumours and should receive more meticulous follow-up. Polymorphism in GSTM1 and CYP2D6 also influences the rate of new primary tumour accrual giving insights into the link between ultraviolet exposure and multiple tumour development.
authors.affiliation: Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, UK.
authors.forename: J T
authors.initials: JT
authors.lastname: Lear
authors.forename: A G
authors.initials: AG
authors.lastname: Smith
authors.forename: A H
authors.initials: AH
authors.lastname: Heagerty
authors.forename: B
authors.initials: B
authors.lastname: Bowers
authors.forename: P W
authors.initials: PW
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Gilford
authors.forename: J
authors.initials: J
authors.lastname: Alldersea
authors.forename: R C
authors.initials: RC
authors.lastname: Strange
authors.forename: A A
authors.initials: AA
authors.lastname: Fryer
mesh_terms: D000368:Aged; D002280:Basal Cell Carcinoma / Q000453:epidemiology* / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics; D013997:Time Factors
chemical_list: D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase