An investigation of the effect of diet on skin cancer : application of improved measures of dietary exposure

McNaughton, S. A. (Sarah Anne) (2003). An investigation of the effect of diet on skin cancer : application of improved measures of dietary exposure PhD Thesis, School of Population Health, The University of Queensland.

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Author McNaughton, S. A. (Sarah Anne)
Thesis Title An investigation of the effect of diet on skin cancer : application of improved measures of dietary exposure
School, Centre or Institute School of Population Health
Institution The University of Queensland
Publication date 2003
Thesis type PhD Thesis
Supervisor Assoc. Prof. Geoff Marks
Total pages 428
Language eng
Subjects 111299 Oncology and Carcinogenesis not elsewhere classified
111199 Nutrition and Dietetics not elsewhere classified
Formatted abstract
Diet is considered to play a substantial role in the development and prevention of many cancers. While ultraviolet radiation is the key factor in development of skin cancer, other environmental factors may also play an important role. The influence of dietary factors on development of skin cancer has been of considerable interest, however existing research in this area is more limited than for other cancers and findings are inconsistent. The overall aim of this thesis is to investigate the relationship between specific dietary factors and keratinocytic skin cancer (KSC) through the application of improved measures of dietary exposure within the context of the Nambour Skin Cancer Study. Dietary factors potentially implicated in the aetiology of skin cancer were reviewed and the exposures chosen for investigation were total fat, saturated fat, polyunsaturated (PUS) fat, monounsaturated (MUS) fat, retinol, carotenoids, vitamin E, selenium and glucosinolates.

The Nambour Skin Cancer Study had a population-based sample of 1621 people aged 25-74 years in 1992. Skin cancer outcomes were assessed via skin examinations in 1992, 1994 and 1996 and a skin cancer surveillance system covering participants, their doctors and pathology laboratories. All skin cancers were confirmed through medical and/or histopathology records. Dietary exposure was assessed using a food frequency questionnaire (FFQ) in 1992,1994 and 1996 and, for a sub-sample, weighed food records (WFRs) and serum biomarkers. Other data included skin cancer risk factors, demographic data, smoking habits and anthropometric measurements.

Food composition data were not available in the current Australian food composition database for several dietary factors under investigation. For carotenoids and vitamin E, existing international food composition databases were identified and applied. For selenium and glucosinolates, two new databases were developed using standard methodology based on published literature from Australian and international sources. For fats, retinol and vitamin C, standard food composition data were available. Serum biomarkers of carotenoids, vitamin E and selenium were utilised both as alternative measures of dietary exposure and in the assessment of validity. For the sub-sample of participants with dietary exposure from FFQ, WFRs and serum biomarkers a triangulation approach was used to calculate the validity coefficient of the FFQ and biomarkers. For the FFQ, the upper limit of the validity coefficients was less than 0.50 for β-carotene (diet and supplements), lutein, total carotenoids (diet and supplements) and β-cryptoxanthin; the upper limit was above 0.50 for α- and β-carotene, lycopene, total carotenoids, and vitamin E and selenium. For the biomarkers, the upper limit for the validity coefficient was less than 0.50 for all dietary factors that could be assessed except for total carotenoids. Therefore, for many dietary factors, only strong relationships between dietary exposure and skin cancer could be detected.

The relationship between diet and skin cancer was investigated using two different study designs: a nested case-control study and a prospective cohort study. In the nested case-control study, cases of basal cell cancer (BCC) identified 1997 - 2001 (n = 90) were compared with age and sex matched controls (n = 90). Dietary exposure was measured using 1996 FFQ estimates of intake and serum biomarkers. Dietary intakes were adjusted for energy intake and serum carotenoids and vitamin E were adjusted for serum cholesterol. Odds ratios were calculated across quartiles of dietary intake and serum biomarkers and linear trends were assessed using logistic regression. Potential confounding variables associated with both BCC and dietary exposure were included in multivariate models. No significant associations were found between diet, as measured by serum biomarkers or dietary intake, and risk of BCC although there was a suggestion of a positive association with lutein intake.

The prospective cohort study used skin cancer outcomes, expressed as counts of BCC or squamous cell cancer (SCC) during three time periods. It used FFQ estimates of dietary intake, demographic, anthropometric and skin cancer risk factors measured at baseline in 1992. Relative risks were calculated across quintiles of energy-adjusted dietary intake using negative binomial regression and results for BCC and SCC were presented separately. Potential confounding variables were investigated and those variables associated with BCC/SCC and dietary exposure were included in multivariate models. A number of significant linear trends between the intake of specific dietary factors and number of KSC lesions were observed. Protective associations with risk of BCC were found for lycopene and glucosinolates and positive associations were found for saturated fat and PUS fat. With respect to SCC, there were protective associations for total and PUS fat and positive associations for a-carotene, β-cryptoxanthin and vitamin C. There was evidence of a lag effect for some factors.

The strengths of this study relate to its prospective nature, ascertainment of KSC lesions via skin examinations and skin cancer surveillance, the application of two separate study designs (nested case-control and prospective cohort) and the use of two independent measures of dietary exposure (dietary intake and serum biomarkers).

Considering all the available evidence surrounding the diet-skin cancer relationship, the following conclusions were made. There is probably no independent relationship between retinol or β-carotene and BCC or SCC. There is evidence for a possible positive relationship between fat and BCC. There is a possible protective relationship between vitamin C and E and BCC, and between selenium and KSC. There is insufficient evidence to determine if fat, vitamin E or vitamin C influence SCC risk, or if α-carotene, β-cryptoxanthin, lutein and lycopene and glucosinolate influence KSC risk.

Further analysis of these dietary hypotheses should focus on additional analysis of serum biomarkers (for all participants and for PUS fatty acid intake), refinement of the glucosinolate exposure measures and further investigation of the time lag periods. Future research should also focus on other dietary factors with antioxidant activity, assessing the overall dietary exposure to antioxidants and overall dietary patterns through factor analysis or dietary pattern scores.

Keyword Skin cancer
Diet in disease
Additional Notes

Variant title: Investigation of the effect of diet on skin cancer

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
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