Melbourne School of Population and Global Health - Theses

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Subject: androgenetic alopecia × Subject: biostatistics × Subject: epidemiology ×

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    Biomarkers of hormone activity and risk of prostate and breast cancers
    Muller, David Clemens ( 2012)
    Background: Hormonal factors have been implicated in the epidemiology of both prostate and breast cancer. While studies of circulating concentrations of sex hormones and cancer risk have been illuminating, they can only assess a limited aspect of hormone exposure. It has been suggested that biomarkers of hormone activity might provide a means to assess critical exposure to hormones. Androgenetic alopecia (AA, also known as male pattern baldness) and the ratio of the lengths of the 2nd and 4th digits (2D:4D) have been proposed as possible biomarkers of androgen action. AA is thought to reflect increased androgen action in tissue. 2D:4D, especially right 2D:4D and the difference between right and left 2D:4D (Δr-l), are thought to be inversely associated with prenatal exposure to testosterone. The primary aims of my doctoral research were to assess whether either of these markers are associated with risk of prostate (for both AA and 2D:4D) or breast (for 2D:4D only) cancers using data from the Melbourne Collaborative Cohort Study (MCCS). Methods: Both 2D:4D and AA were assessed at a face-to-face follow up of the MCCS conducted between 2003 and 2009. Cancer cases were identified as men and women with a first diagnosis of prostate or breast cancer post baseline attendance (between 1990 and 1994). Survival analysis techniques were used to estimate associations between the biomarkers and cancer risk. Classical and hierarchical linear regression models were used to estimate whether 2D:4D was associated with anthropometric measures or concentrations of circulating sex hormones respectively. Results: No strong association was observed between any 2D:4D measure and risk of prostate cancer. There was an indication that both right and left 2D:4D might be inversely associated with risk of early onset prostate cancer. Higher left 2D:4D was associated with slightly increased risk of breast cancer, and Δr-l was inversely associated with risk. No association was observed between right 2D:4D and risk. The inverse association between Δr-l and risk appeared to be somewhat stronger for poorly or undifferentiated tumours. There were no strong associations observed between 2D:4D measures and concentrations of circulating sex hormones. Nor was any anthropometric measure materially associated with 2D:4D. A strongly age dependent association between AA and prostate cancer risk was observed. Vertex AA at age 40 years was associated with increased risk of early onset prostate cancer, and younger age at diagnosis for prostate cancer cases. The cumulative risk of prostate cancer was greater up to approximately age 75 years for men with vertex AA at age 40 years compared with men with no AA at that age. At age 75 years the cumulative probability of prostate cancer was estimated to be 0.15, regardless of hair pattern at age 40 years. Conclusions: The results presented in this thesis suggest that prenatal testosterone exposure might play a role in the aetiology of prostate and particularly breast cancers. Additionally, the result that vertex AA at age 40 years is associated with increased risk of early onset prostate cancer lends support to the hypothesis that AA and prostate cancer might have analogous androgen-based aetiologies.