In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis.
BACKGROUND
Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established.


METHODS
We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.


RESULTS
Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM.


CONCLUSIONS
UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.
Wang
Li-E
LE
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Xiong
Ping
P
Strom
Sara S
SS
Goldberg
Leonard H
LH
Lee
Jeffrey E
JE
Ross
Merrick I
MI
Mansfield
Paul F
PF
Gershenwald
Jeffrey E
JE
Prieto
Victor G
VG
Cormier
Janice N
JN
Duvic
Madeleine
M
Clayman
Gary L
GL
Weber
Randal S
RS
Lippman
Scott M
SM
Amos
Christopher I
CI
Spitz
Margaret R
MR
Wei
Qingyi
Q
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002842:Chromatids / Q000528:radiation effects*; D016001:Confidence Intervals; D004198:Disease Susceptibility; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000209:etiology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000528:radiation effects*; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology*; D013471:Sunburn; D014466:Ultraviolet Rays / Q000009:adverse effects*