Melbourne School of Population and Global Health - Research Publications
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ItemSecond to fourth digit ratio (2D: 4D) and prostate cancer risk in the Melbourne Collaborative Cohort Study(NATURE PUBLISHING GROUP, 2011-07-26)BACKGROUND: The ratio of the lengths of index and ring fingers (2D:4D) is a marker of prenatal exposure to sex hormones, with low 2D:4D being indicative of high prenatal androgen action. Recent studies have reported a strong association between 2D:4D and risk of prostate cancer. METHODS: A total of 6258 men participating in the Melbourne Collaborative Cohort Study had 2D:4D assessed. Of these men, we identified 686 incident prostate cancer cases. Hazard ratios (HRs) and confidence intervals (CIs) were estimated for a standard deviation increase in 2D:4D. RESULTS: No association was observed between 2D:4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92-1.08 for right, 0.93-1.08 for left). We observed a weak inverse association between 2D:4D and risk of prostate cancer for age <60, however 95% CIs included unity for all observed ages. CONCLUSION: Our results are not consistent with an association between 2D:4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D:4D and early onset prostate cancer risk.
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ItemSecond to fourth digit ratio (2D: 4D), breast cancer risk factors, and breast cancer risk: a prospective cohort study(NATURE PUBLISHING GROUP, 2012-10-23)BACKGROUND: We aimed to assess whether 2D:4D measures are associated with breast cancer risk. METHODS: We derived the ratio of the lengths of the index and ring fingers (2D:4D), and right minus left 2D:4D (Δ(r-l)) from digit lengths measured from photocopies of participants' hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. Of the 9044 women with available data, we identified 573 incident breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D:4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D:4D measures and age at menarche and menopause. RESULTS: We found a direct association between left 2D:4D and breast cancer risk, an inverse association between Δ(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk. Among breast cancer cases, both right 2D:4D and Δ(r-l) were inversely associated with age at diagnosis. We also observed associations between both right 2D:4D and Δ(r-l) and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause. CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer.
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ItemNo Preview AvailableAssociation between index-to-ring finger length ratio and risk of severe knee and hip osteoarthritis requiring total joint replacement(OXFORD UNIV PRESS, 2014-07)OBJECTIVE: The data are conflicting for the association between the index-to-ring finger length ratio (2D:4D) and the risk of OA. The aim of this cohort study was to examine the relationship between 2D:4D and the risk of severe knee and hip OA requiring total joint replacement. METHODS: A total of 14 511 participants in the Melbourne Collaborative Cohort Study had 2D:4D assessed from hand photocopies. The incidence of total knee replacement and total hip replacement between 2001 and 2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 10.5 years of follow-up, 580 participants had total knee replacement and 499 had total hip replacement. Greater right 2D:4D [hazard ratio (HR) 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.03] and average right and left 2D:4D (HR 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.02) were associated with a reduced incidence of total knee replacement. These associations persisted when participants whose fingers had any features that might have affected the validity of 2D:4D measurements were excluded. No significant associations were observed between 2D:4D and the incidence of total hip replacement. CONCLUSION: A lower 2D:4D is associated with an increased risk of severe knee OA requiring total knee replacement, but not the risk of severe hip OA. The underlying mechanisms for the association warrant further investigation.
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ItemA three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease(WILEY-BLACKWELL, 2014-10)Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, "cases" (N = 83), were matched to "referents" (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14-5.54, P = 0.02 and 3.08, 95% CI 1.41-6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20-0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.
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ItemAge-Dependent Associations between Androgenetic Alopecia and Prostate Cancer Risk(AMER ASSOC CANCER RESEARCH, 2013-02)BACKGROUND: Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. METHODS: At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. RESULTS: Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. CONCLUSIONS: Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. IMPACT: If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.
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ItemAge dependent associations between androgenetic alopecia and prostate cancer risk(American Association for Cancer Research, 2013)