Bruce K. Armstrong

It is not known if the incidence of common cancers in Australian farm residents is different to rural non-farm or urban residents. Data from farm, rural non-farm and urban participants of the 45 and Up Study cohort in New South Wales, Australia, were linked with state cancer registry data for the years 2006–2009. Directly standardised rate ratios for cancer incidence were compared for all-cancer, prostate, breast, colorectal cancer, melanoma and non-Hodgkin Lymphoma (NHL). Proportional hazards regression was used to generate incidence hazard ratios for each cancer type adjusted for relevant confounders. Farm women had a significantly lower all-cancer hazard ratio than rural non-farm women (1.14, 1.01–1.29). However, the lower all-cancer risk observed in farm men, was not significant when compared to rural non-farm and urban counterparts. The all-cancer adjusted hazard ratio for combined rural non-farm and urban groups compared to farm referents, was significant for men (1.08,1.01–1.17) and women (1.13, 1.04–1.23). Confidence intervals did not exclude unity for differences in risk for prostate, breast, colorectal or lung cancers, NHL or melanoma. Whilst non-significant, farm residents had considerably lower risk of lung cancer than other residents after controlling for smoking and other factors. All-cancer risk was significantly lower in farm residents compared to combined rural non-farm and urban groups. Farm women had a significantly lower all-cancer adjusted hazard ratio than rural non-farm women. These differences appeared to be mainly due to lower lung cancer incidence in farm residents.

Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From three case-control studies of cutaneous melanoma, we estimated the prevalence and predictors of these mutations for people from regions with widely differing latitudes and melanoma incidence. Population-based cases and controls from the United Kingdom (1586 cases, 499 controls) and Australia (596 early-onset cases, 476 controls), and a hospital-based series from Spain (747 cases, 109 controls), were screened for variants in all exons of CDKN2A and the p16INK4A binding domain of CDK4. The prevalence of mutations for people with melanoma was similar across regions: 2.3%, 2.5% and 2.0% for Australia, Spain and the United Kingdom respectively. The strongest predictors of carrying a mutation were having multiple primaries (odds ratio (OR) = 5.4, 95% confidence interval (CI: 2.5, 11.6) for 2 primaries and OR = 32.4 (95% CI: 14.7, 71.2) for 3 or more compared with 1 primary only); and family history (OR = 3.8; 95% CI:1.89, 7.5) for 1 affected first- or second-degree relative and OR = 23.2 (95% CI: 11.3, 47.6) for 2 or more compared with no affected relatives). Only 1.1% of melanoma cases with neither a family history nor multiple primaries had mutations. There is a low probability (CDKN2A mutation in people with melanoma except for those with a strong family history of melanoma (≥2 affected relatives, 25%), three or more primary melanomas (29%), or more than one primary melanoma who also have other affected relatives (27%).

Background: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. Methods: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child’s age, sex, ethnicity, parental education, and study center. Results: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78–0.92) for vitamin use and 0.80 (0.71–0.89) for folic acid use. The reduced risk was more pronounced in children whose parents’ education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75–1.14) and 0.68 (0.48–0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). Conclusions: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment. Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis. This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary. Patients aged 18 – 79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo. The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug. The secondary endpoints are participation and progression free survival. The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138. Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available. Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will: 1. prolong time to recurrence within 5 years 2. improve overall survival at 5 years and 3. be both safe and tolerable. Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014. The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09). Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000351213

Despite years of public education, sun-related behaviours are difficult to change and a recent survey showed low levels of sun protection. In this study we evaluated the feasibility and acceptability of an opportunistic skin cancer prevention intervention in general practice.

There is evidence, although inconsistent, that long term exposure to disinfection by products (DBPs) increases the risk of bowel cancer. No study has been conducted in Australia to examine this association and due to difference in the methods of disinfection the risk can vary across geographical regions and. This study was conducted to analyse the association of trihalomethanes (THMs) in water with colon and rectal cancer in NSW Australia.

Cervical screening is currently recommended every two years in sexually active women aged 18-20 to 69 years in Australia. Direct replacement of conventional cytology with liquid-based cytology (LBC) for cervical screening was rejected for public funding on grounds of cost-effectiveness, first in 2002 and again in 2009, but LBC is performed as an adjunct to conventional cytology in women who elect to pay. The objective of this study was to describe prevalence and predictors of use of LBC in Australia’s most populous state, New South Wales (NSW).

We aim to determine the relationship between season, personal solar UV exposure, serum 25(OH)D and 1,25(OH)₂D and serum prostate-specific antigen (PSA) levels. Questionnaire data and blood samples were collected at baseline from participants of the Concord Health and Ageing in Men Project (n = 1,705), aged 70 and above. They were grouped as men ‘free of prostate disease’ for those with no record of having prostate cancer, benign prostatic hyperplasia, or prostatitis and with serum PSA levels below 20 ng/mL, and ‘with prostate disease’ for those with a record of either of these diseases or with serum PSA levels 20 ng/mL or above. Personal solar UV exposure (sUV) was estimated from recalled hours of outdoor exposure and weighted against ambient solar UV radiation. Sera were analysed to determine levels of PSA, 25(OH)D and 1,25(OH)₂D, and analysed using multiple regression, adjusting for age, BMI and region of birth. The association between sUV and serum PSA levels was conditional upon season (p _interaction = 0.04). There was no direct association between serum PSA and 25(OH)D in both groups of men. There was a positive association between serum PSA and 1,25(OH)₂D in men with prostate disease (mean = 110.6 pmol/L; p _{heterogeneity} = 0.03), but there was no such association in men free of prostate disease (mean = 109.3 pmol/L; p _{heterogeneity} = 0.8). The association between PSA and sUV may only be evident at low solar UV irradiance, and this effect may be independent of serum vitamin D levels.