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DNA repair and nonmelanoma skin cancer in Puerto Rican populations

https://doi.org/10.1067/S0190-9622(03)00918-6Get rights and content

Abstract

Background

UV radiation is a risk factor for nonmelanoma skin cancer (NMSC). The relation between DNA damage and oncogenesis suggests that diminished DNA repair capacity (DRC) is involved in tumorigenesis.

Objective

The purpose of this study was to test the hypothesis that a low DRC is a susceptibility factor for the development of NMSC in Puerto Rico.

Methods

A case-control retrospective clinical study was done to compare the age-adjusted DRC in participants with and without NMSC. DRC was measured using a host cell reactivation assay with a luciferase reporter gene irradiated with UV light and transfected into human peripheral lymphocytes. An epidemiologic questionnaire was used to solicit risk factors.

Results

The mean (±2 SE) DRC of 177 control patients without skin cancer was 8.6% ± 0.7. Participants (280) with NMSC had a 42% lower DRC (5.0% ± 0.3).

Conclusion

A low DRC is a susceptibility factor for NMSC.

Section snippets

Study eligibility

The use of human patients was approved by the institutional review board at Ponce School of Medicine, Ponce, Puerto Rico. Informed consent was obtained from each participant before enrollment. All participants were residents of Puerto Rico and at least 21 years old. The participants had histopathologically confirmed primary BCC and SCC (International Classification of Diseases, Ninth Revision code 173.9). More than 95% of the participants with NMSC (n = 280) were recruited from a private

Characteristics of the study population

The overall age, sex, and skin type distribution of patients is presented in Table II. The control group had a higher proportion of volunteers aged 20 to 40 years and a significantly lower proportion of participants older than 60 years (Table II). Sunlight exposure was recreational and occupational; about 55% and 33% of the patient and control populations, respectively, had worked outdoors (Table II). A 3.8:1 ratio of BCC/SCC tumors was found in the patients examined (n = 280) (Fig 1).

Dna repair capacity

The mean age-adjusted DRC for the control patients in the Puerto Rican population studied was 8.6% (n = 177). Participants (n = 280) with NMSC had a mean age-adjusted DRC 42% lower (DRC = 5.0%), than the control patients. The DRC of control patients had a significant (P = .017) decrease of 0.05% per each year of age. Patients had a DRC decrease of 0.01% per year of age that was not significant (P = .324). Table I shows a comparison of the DRC values of 457 participants (control participants vs

DNA repair as a susceptibility factor for NMSC

To assess the usefulness of using DRC as a marker of NMSC susceptibility, participants with a low DRC (<4.4%) were compared with those with a high DRC (>11.4%). Low DRC values were classified as the lowest 33% DRC value of the total population (control participants and patients). A high DRC consisted of values in the uppermost 10%. Participants with a high and a low DRC had respective odds ratios of 0.12 (95% confidence interval = 0.05-0.32, P < .001) and 3.8 (95% confidence interval =

Risk factors

The risk factors shown in Table II were associated with 2- to nearly 7-fold increased risk of NMSC development. Adjusting for all variables, patients had twice the risk of a new skin tumor developing when compared with control participants. Six or more lifetime severe sunburns, family history of any cancer, and family history of skin cancer also represented significantly increased risks for NMSC (P < .001). A low DRC (<4.4%) was also compared with selected representative risk factors. Only the

Discussion

This study supports the hypothesis that a reduced DRC is a susceptibility factor for the development of NMSC in the Puerto Rican populations studied. Patients with NMSC had a statistically significant lower (42%) DRC compared with control participants. The impact of reduced DRC is significant; for every 1% decrease in DRC, the risk of developing NMSC increases 21%. Possibly a lower UV exposure history is required for the development of NMSC in persons with a reduced DRC because of genetic or

Acknowledgements

The authors express their sincere appreciation to all the participants for donating blood and time to make this study possible. The Puerto Rico Cancer Center donated some supplies used for the host cell reactivation assay. Mrs Hannia Delgado coordinated all aspects of this study and assisted with the preparation of the manuscript. Mrs Ivette Lopez administered the informed consent and obtained blood from all participants. Dr Carlos Rios assisted with epidemiologic and statistical data analysis

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    Supported by grants from the RCMI-NIH Program (grant 2G12 RR03050-17) and the National Aeronautic and Atmospheric Administration (grant NAG-2-1385) to Ponce School of Medicine through Dr Matta.

    Conflicts of interest: None identified.

    Accepted for publication December 14, 2002.

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