Cutaneous squamous cell carcinoma and its determinants

Penelope Mcbride (2009). Cutaneous squamous cell carcinoma and its determinants PhD Thesis, School of Population Health, The University of Queensland.

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s33161936_PhD_Abstract.pdf Thesis Abstract application/pdf 60.77KB 2
s33161936_PhD_totalthesis.pdf Thesis submission application/pdf 1021.67KB 18
s33161936_phd_references.pdf References application/pdf 146.00KB 5
Author Penelope Mcbride
Thesis Title Cutaneous squamous cell carcinoma and its determinants
School, Centre or Institute School of Population Health
Institution The University of Queensland
Publication date 2009-12
Thesis type PhD Thesis
Supervisor Prof Adele Green
Prof Gail Williams
Total pages 235
Total colour pages 7
Total black and white pages 228
Subjects 11 Medical and Health Sciences
Abstract/Summary Context: Squamous cell carcinoma (SCC) is the second most common skin cancer. Ultraviolet radiation (UVR) exposure, its most important risk factor, has mostly been investigated in cross-sectional study designs. This study presents a comprehensive and longitudinal examination of determinants of SCC, including photoageing. Objective: To examine the determinants of SCC and its precursor condition of photoageing. Above all, the objective was to investigate the interplay of phenotypic traits; occupation and leisure-time sun exposure patterns; and personal exposures, in particular, tobacco smoking and life course sun exposure, upon the risk of SCC and photoageing. Setting and Design: This investigation formed part of a large community-based, long-term cohort study of skin cancer. The Nambour Skin Cancer Study (forthwith, the Nambour Study) began in 1986 and concluded in 2007. In 1986 a random sample of 2095 people (aged 20-69 years) from Nambour, Queensland participated in a skin cancer survey. In 1992, a 5 year field trial to assess the preventive actions of sunscreen and beta-carotene was initiated (n=1621). Regular full skin examinations were conducted to determine the presence of skin cancer and actinic skin damage. In 1994, participants detailed their life course sun exposure (n=1290). After the trial ended in 1996, participants continued to complete regular questionnaires and ascertainment of skin cancers continued to 2007. Participants: The participants were 1339 unselected adults aged 25 to 75 years who had taken part in the Nambour Study in 1992 and consented to the follow-up study. Methods: Life course sun exposure hours were estimated from questionnaires and the approximate UVR exposure for Nambour (latitude 26S) was determined. Descriptive analyses examined patterns of exposure within the population. Factors influencing the severity of photoageing were also investigated. Informed by these analyses, relative risks were calculated for determinants of SCC and population attributable risk percentage (PAR%) for key modifiable risk factors. To investigate tobacco smoking as a risk factor for SCC, systematic review and meta-analysis were performed. Exposure measures: Pigmentary phenotype, estimated UVR exposure, tobacco smoking, sun-related behaviours, e.g. sunscreen use. Outcome measures: Incident and histologically proven SCC of the skin from 1992 to 2007 was the main outcome assessed. Photoageing, assessed clinically and micro-topographically (Beagley and Gibson scale), was an intermediate outcome measure and an objective measure of cumulative sun exposure in the final SCC analysis. Results: Examination of self-reported UVR revealed mean annual exposures were highest in early life and older adulthood (older than 60 years.) Women reported spending less time in the sun than men in all stages of life (p<0.05) and the more sun-sensitive the person’s skin type, the less sun exposure was reported at each life stage. The role of tobacco smoking in cutaneous SCC was reviewed in the published literature and a small positive association was noted in the meta-analysis. However, few studies had adjusted, or adjusted adequately, for sun exposure. Within the Nambour Study, with adjustment for age, sex, skin phenotype, lifetime sun exposure, current and former smoking had no association with SCC (RR 1.2, 95%CI 0.7, 2.0 and RR 1.1, 95%CI 0.8, 1.5, respectively compared with lifelong non-smokers). In this study population, with moderate to severe photoageing at study baseline, increasing age, male sex, a sun-sensitive phenotype were found to increase the odds of more severe actinic damage (p<0.05). High or very high UVR exposure in adulthood predicted a greater severity (OR 2.2, 95%CI 1.3, 4.0). Finally, the determinants of SCC were examined. Increasing age (4% increase per year of life, 95%CI 3% to 5%), male sex (RR 1.4, 95%CI 1.1, 1.9) and fair skin (RR 4.7 95%CI 2.0, 11.4) were associated with SCC. Having light eye colour and fair or red hair also significantly increased SCC risk. Recalled life course sun exposure overall was not found to be associated with SCC. Signs of actinic damage at baseline were, however, very strongly associated with SCC. Recent sun exposure, defined as that reported in the period (1-2 years) before the occurrence of SCC or for those unaffected at the end of the study, was also examined. A strong positive association was found between high recent exposure and SCC (RR 2.1, 95%CI 1.3, 3.3). PAR% estimates of prominent modifiable risk factors for SCC suggested considerable potential for reduction in incidence for at-risk populations if recent sun exposure were reduced. Conclusions: Subjective measures of solar UVR exposure and objective measures of photoageing varied according to personal and phenotypic factors. The interplay between risk factors observed here highlight the need to control for confounding in investigating solar factors as causes of skin cancer. Although SCC occurred on the background of high cumulative UVR exposure, which was best determined with objective rather than recalled measures, recent UVR exposure was also important. Self-reported recent exposure being less subject to recall bias than reported life course exposure may have partly influenced this, but the impact of UVR acting as a tumour initiator and promoter is also likely to explain the relation of SCC to sun exposure in the recent past.
Keyword Cutaneous squamous cell carcinoma, tobacco smoking, photoageing, epidemiology
Additional Notes Colour Fig 4.4 - p.83 Fig 4.5 - p.87 Fig 7.1 (a) and (b) - p.131 Fig 7.1 (c) and (d) - p.132 Fig 7.2 - p.142 Fig 8.1 - p.151 Fig 9.1 - p.165 Landscape Table 5.1 - p.96 and p.97 Table 5.2 - p.100 and p.101 Table 5.4 - p.109 Table 7.3 - p.134 Fig 8.1 - p.151

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Created: Tue, 01 Jun 2010, 12:04:58 EST by Ms Penelope Mcbride on behalf of Library - Information Access Service