Flinders Centre for Innovation in Cancer Collected Works

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Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells
(2004) Zhang, L; Barritt, Gregory John
Screening for colorectal cancer
(2004) Young, Graeme Paul; Bampton, Peter Alexander; Cole, Stephen Russell; Morcom, Joylene Margaret; Smith, Alicia Therese; Turnbull, Deborah; Wilson, Carlene J
Suppression of azoxymethane-induced colon cancer development in rats by dietary resistant starch
(2007) Le Leu, Richard Kevin; Hu, Ying; Young, Graeme Paul; Brown, Ian Lewis; Esterman, Adrian Jeffrey
Suppression of Colorectal Oncogenesis by Selenium-Enriched Milk Proteins: Apoptosis and K-ras Mutations
(2008) Woodman, Richard John; Young, Graeme Paul; Hu, Ying; McIntosh, Graeme Howie; Le Leu, Richard Kevin
Demographic associations with stage of readiness to screen for colorectal cancer
(Australian Health Promotion Association, 2009) Duncan, Amy; Wilson, Carlene J; Cole, Stephen Russell; Mikocka-Walus, Antonina; Turnbull, Deborah; Young, Graeme Paul
Objective: To describe the distribution of a population in southern urban Adelaide in terms of readiness to screen for colorectal cancer (CRC) by Faecal Occult Blood Test (FOBT) or colonoscopy according to the stages in the Transtheoretical Model (TTM) of behaviour change and to compare the stages according to demographic variables. Methods: A random sample of 664 South Australians aged 50 to 74 were surveyed in June 2006. Chi-squared analyses were performed to determine if statistically significant differences on demographic variables existed between participants at different stages of readiness to screen.
Attitudes towards and beliefs about colorectal cancer and screening using the faecal occult blood test within the Italian-Australian community
(Asian Pacific Organization for Cancer Prevention, 2009) Severino, Giovanina; Wilson, Carlene J; Turnbull, Deborah; Duncan, Amy; Gregory, Tess Anne
Studies with minority ethnic communities worldwide reveal important differences in the content of beliefs about cancer and attitudes towards screening. Current initiatives in colorectal cancer (CRC) screening highlight the importance of identifying any illness-specific beliefs that might influence participation rates within the targeted age-range. We conducted semi-structured interviews with 20 Italian-Australians aged between 50 and 78 years, living in Adelaide, South Australia. Qualitative data from the interviews were analysed using framework analysis. Participants articulated specific beliefs about the nature of cancer, risk factors, prevention possibilities, and variety of potential barriers and benefits to faecal occult blood testing (FOBT). Although participants’ beliefs overlapped with conventional medical models of cancer, the results also demonstrated the presence of specific cultural perceptions that might influence FOBT participation. Our results suggest that models used to inform communication about cancer need to be sensitive to culture specific concerns. Within the context of the older Italian-Australian community, there is a suggestion that self and response efficacy may be serious barriers to screening behavior and that bi-lingual, verbal delivery of information may be the most effective mode of communication to increase screening participation.
A cross-sectional analysis of participation in National Bowel Cancer Screening Program in Adelaide by age, gender and geographical location of residence
(Australasian Medical Journal, 2010) Javanparast, Sara; Ward, Paul Russell; Cole, Stephen Russell; Gill, Tiffany; Ah Matt, Michelle Lorraine; Aylward, Philip Edmund; Baratiny, Genevieve; Jiwa, Moyez; Martini, Angelita; Misan, Gary; Tsourtos, George; Wilson, Carlene J; Young, Graeme Paul
The National Bowel Cancer Screening Program (NBCSP) is a population-based screening program based on a mailed screening invitation and immunochemical faecal occult blood test. Initial published evidence from the NBCSP concurs with international evidence on similar colorectal cancer screening programs about the unequal participation by different population sub-groups. The aim of the paper is to present a cross-sectional analysis of participation in the NBCSP for Adelaide, in order to identify geographical areas and population groups which may benefit from targeted approaches to increase participation rates in colorectal cancer screening.
Screening for colorectal cancer in remote, rural and metropolitan South Australia: analysis of the National Bowel Cancer Screening Program data
(Government of South Australia Department of Health, 2011) Martini, Angelita; Javanparast, Sara; Ward, Paul Russell; Cole, Stephen Russell; Aylward, Philip Edmund; Baratiny, Genevieve; Gill, Tiffany; Tsourtos, George; Misan, Gary; Wilson, Carlene J; Young, Graeme Paul
The early detection of colorectal cancer (CRC) is a major clinical and public health concern. CRC is now the second most commonly diagnosed cancer in Australia and has the second highest cancer mortality rate. Around 1 in 19 men and 1 in 28 Australian women will develop the disease before 75 years of age. In 2005 there were 4165 deaths from CRC in Australia, accounting for almost 11% of all cancer deaths. Cancer mortality rates vary according to the remoteness of a person’s place of residence. The average annual death rate for CRC during 1998–2001 in Australia was highest in inner and outer regional areas (13.4% and 13.3%), followed by major cities (12.8%), remote areas (12.4%) and very remote areas (7.7%). Survival is inversely related to the degree of cancer progression, and up to 90% of all deaths from CRC may be preventable with early detection. This study aimed to explore the association between screening participation and different sociodemographic indicators in SA. This was part of a broader study that included a qualitative exploration of the barriers to and facilitators of NBCSP participation among selected ethnic groups, Indigenous Australians and people who speak English at home. This paper also draws on these qualitative findings in discussing the uptake of screening in rural, remote and metropolitan areas of SA.
Equity of colorectal cancer screening: which groups have inequitable participation and what can we do about it?
(CSIRO Publishing, 2011) Ward, Paul Russell; Javanparast, Sara; Wilson, Carlene J
The National Bowel Cancer Screening Program (NBCSP) offers population-based screening for colorectal cancer (CRC) across Australia. The aims of this paper were to highlight the inequities in CRC screening in South Australia (SA) and the system-related barriers and enablers to CRC screening from the perspective of participants identified as having inequitable participation. First, de-identified data for the SA population of the NBCSP were statistically analysed and then mapped. Second, 117 in-depth interviews were conducted with culturally and linguistically diverse (CALD) groups, Indigenous and Anglo-Saxon Australians. Participation rates in the NBCSP were geographically and statistically significantly different (P < 0.0001) on the basis of gender (higher for women), age (higher for older people) and socioeconomic status (higher for more affluent people). The main system-related barriers were the lack of awareness of CRC or CRC screening within these groups, the problems with language due to most of the information being in English and the lack of recommendation by a doctor. This study revealed that inequity exists in the NBCSP participation in SA, and we identified both barriers and facilitators to CRC screening that require action at the level of both policy and practice. There is a large role in primary health care of both recommending CRC screening and facilitating equitable participation.
Colorectal cancer screening in rural and remote areas: analysis of the National Bowel Cancer Screening Program data for South Australia.
(James Cook University, 2011) Martini, Angelita; Javanparast, Sara; Ward, Paul Russell; Baratiny, Genevieve; Gill, Tiffany; Cole, Stephen Russell; Tsourtos, George; Aylward, Philip Edmund; Jiwa, Moyez; Misan, Gary; Wilson, Carlene J; Young, Graeme Paul
In Australia, colorectal cancer is the second most commonly diagnosed cancer and cause of death from malignant diseases, and its incidence is rising. The aim of this article was to present an analysis of National Bowel Cancer Screening Program (NBCSP) data for rural and remote South Australia (SA), in order to identify geographical areas and population groups that may benefit from targeted approaches to increase participation rates in colorectal cancer screening.The findings of this study suggest lower NBCSP participation rates for people from metropolitan and remote areas, compared with those from rural areas. The uptake of cancer screening is lower for older rural and remote residents, men, Indigenous people, lower socioeconomic groups and those living in the Far North subdivision of SA.
Predictors of re-participation in faecal occult blood test-based screening for colorectal cancer
(National Cancer Center, Korea, 2012) Cole, Stephen Russell; Gregory, Tess Anne; Whibley, Alex; Ward, Paul Russell; Turnbull, Deborah; Wilson, Carlene J; Flight, Ingrid; Esterman, Adrian Jeffrey; Young, Graeme Paul
Background: There is little information on longitudinal patterns of participation in faecal occult blood test (FOBT) based colorectal cancer (CRC) screening or on demographic or behavioural factors associated with participation in re-screening. The lack of an agreed system for describing participatory behaviour over multiple rounds also hampers our ability to report, understand and make use of observed associations. Our aims were to develop a system for describing patterns of participatory behaviour in FOBT-based CRC screening programs and to identify factors associated with particular behavioural patterns. Methods: A descriptive framework was developed and applied to a data extract of screening invitation outcomes over two rounds of the NBCSP. The proportion of invitees in each behaviour category was determined and associations between behaviour patterns and demographic and program factors were identified using multivariate analyses. Results: We considered Re- Participants, Dropouts, Late Entrants and Never Participants to be the most appropriate labels for the four possible observed participatory categories after two invitation rounds. The screening participation rate of the South Australian cohort of the NBCSP remained stable over two rounds at 51%, with second round Dropouts (10.3%) being balanced by Late Entrants (10.5%). Non-Participants comprised 38.7% of invitees. Relative to Re-Participants, Dropouts were older, more likely to be female, of lower SES, had changed their place of residence between offers had a positive test result in the first round. Late Entrants tended to be in the youngest age band. Conclusions: Specific demographic characteristics are associated with behavioural sub-groups defined by responses to 2 offers of CRC screening. Targeted group-specific strategies could reduce dropout behaviour or encourage those who declined the first invitation to participate in the second round. It will be important to keep first round participants engaged in order to maximise the benefit of a CRC screening program.
Using the Transtheoretical Model of Behaviour Change to describe readiness to rescreen for colorectal cancer with Faecal Occult Blood Testing
(CSIRO Publishing, 2012) Duncan, Amy; Turnbull, Deborah; Gregory, Tess Anne; Cole, Stephen Russell; Young, Graeme Paul; Flight, Ingrid; Wilson, Carlene J
Issue addressed: This study used the Transtheoretical Model of Behaviour Change (TTM) to describe reparticipation in colorectal cancer (CRC) screening according to social cognitive and background variables. Methods: A random sample of men and women aged 50-74 years living in South Australia completed a questionnaire measuring TTM stage and attitudes toward screening using a faecal occult blood test (FOBT). Participants were categorised according to four stages of readiness to rescreen: action, maintenance, relapse and inconsistent. Multivariate techniques were used to determine predictors of lower readiness stages compared with maintenance. Results: Of the 849 study participants, 29.9% were either non-adherent or had no intentions to maintain adherence (inconsistent and relapse). Compared with maintenance rescreeners, relapse participants reported less: social influences to screen (RR=0.86, p<0.001); satisfaction with prior screening (RR=0.87, p=0.03), self-efficacy (RR=0.96, p=0.01); and screening benefits (RR=0.84, p<0.001). Relapse participants were also more likely to not have private health insurance (RR=1.33, p=0.04) and be unaware of the need to repeat screening (RR=1.41, p=0.02). Inconsistent screeners were less likely to have planned when they will next rescreen (RR= 0.84, p=0.04) and reported greater barriers to rescreening (RR=1.05, p=0.05). Action participants were younger (RR= 0.98, p=<0.001), reported less social influences to screen (RR=0.94, p<0.001) and were less likely to have known someone who has had CRC (RR=0.82, p=0.01). Conclusions: Social cognitive, demographic and background variables significantly differentiated screening maintenance from lower readiness stages
Discovery and validation of molecular biomarkers for colorectal adenomas and cancer with application to blood testing
(Public Library of Science, 2012-01-19) LaPointe, Lawrence C; Pedersen, Susanne K; Dunne, Robert; Brown, Glenn S; Pimlott, Letitia; Gaur, Snigdha; McEvoy, Aidan; Thomas, Melissa; Wattchow, David Anthony; Molloy, Peter L; Young, Graeme Paul
Results: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers compared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated in independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was selected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an uncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/ 40) compared to neoplasia-free controls (6/20).
Sample preference for colorectal cancer screening tests: blood or stool?
(Scientific Research Publishing, 2012-08) Osborne, Joanne M; Wilson, Carlene J; Moore, Vivienne M; Gregory, Tess Anne; Flight, Ingrid; Young, Graeme Paul
Objective: Despite the high prevalence of CRC and the proven benefits of faecal sampling tests, participation rates in CRC screening are suboptimal. Literature has identified a number of barriers to participation, including faecal aversion. Emerging test technologies suggest blood-based molecular markers might provide an alternative, more acceptable option, for CRC screening tests. We aim to determine preference for blood compared to faeces as the sample for the screening test. Methods: A survey was mailed to 956 South Australians aged 50 to 74 years. Data were collected on sample preference, demographic variables, and ratings of screening test convenience and comfort. Results: The survey yielded a 43% response rate. The majority of participants preferred to provide a blood sample (78% v 22%, p < 0.001). Women were more likely to prefer blood than men (82% vs 74%, p = 0.05). Sample experience influenced preferences, with a significantly higher preference for faeces among participants with experience in faecal sampling (27% vs 17% with no experience, p < 0.05). Participants who preferred to provide a faecal sample rated it significantly more convenient (p < 0.001), more comfortable (p < 0.001), and more acceptable (p < 0.001) than those who preferred blood sampling. Conclusions: Survey participants overwhelmingly indicate a preference for the idea of a blood sample over a faecal sample for CRC screening. Preference was influenced by gender, experience with sampling method and the individual’s perception of sampling convenience, sampling comfort and sample acceptability. Our results suggest population participation rates are likely to improve with blood-based screening tests.
Modeling the cost-effectiveness of strategies for treating esophageal adenocarcinoma and high-grade dysplasia
(Springer-Verlag, 2012-08) Gordon, Louisa G; Hirst, Nicholas G; Mayne, George C; Watson, David Ian; Bright, Tim Flaxman; Cai, Wang; Barbour, Andrew P; Smithers, B Mark; Whiteman, David C; Eckermann, Simon Douglas; Australian Cancer Study Clinical Follow-Up Study Group
Objective: To synthesize cost and health outcomes for current treatment pathways for esophageal adenocarcinoma and high grade dysplasia, and model comparative net clinical and economic benefits of alternative management scenarios. Methods: A decision-analytic model of real-world practices for esophageal adenocarcinoma treatment by tumor stage was constructed and validated. The model synthesized treatment probabilities, survival, quality-of-life and resource use extracted from epidemiological datasets, published literature and expert opinion. Comparative analyses between current practice and five hypothetical scenarios for modified treatment were undertaken. Results: Over five years, outcomes across T stage ranged from 4.06 quality-adjusted life-years and costs of $3,179 for high grade dysplasia, to 1.62 and $50,226 for stage T4. Greater use of endoscopic mucosal resection for stage T1 and measures to reduce esophagectomy mortality to 0-3% produced modest gains whereas a 20% reduction in the proportion of patients presenting at stage T3 produced large incremental net benefits of $4,971 (95% interval: $1,560, $8,368). Conclusion: These findings support measures that promote earlier diagnosis, such as developing risk assessment processes or endoscopic surveillance of Barrett’s esophagus. Incremental net monetary benefits for other strategies are relatively small in comparison to predicted gains from early detection strategies.
Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model
(International Institute of Anticancer Research, 2013) Martin, Jonathan Edward; Young, Graeme Paul; Le Leu, Richard Kevin; Hu, Ying
The protection against colorectal cancer (CRC) by non-steroidal anti-inflammatory drugs (NSAIDs) is in part dependent on inhibition of cyclooxygenase (COX). We compared the efficacy of the non-COX-inhibiting R flurbiprofen (R-FB) with COX-inhibiting sulindac and racemic flurbiprofen (Rac-FB), and determined their effects on apoptosis, in an azoxymethane (AOM)-induced rat CRC model. In experiment 1, groups of rats were given daily drug gavage (R-FB 30 mg/kg, Rac-FB 10 mg/kg and Sulindac 20 mg/kg) for one week, followed by AOM treatment and were killed eight hours later, colons were examined for apoptosis and cell proliferation. In experiment 2, groups of rats were given two AOM treatments, followed by daily drug gavage until they were killed ten weeks later, colons were examined for aberrant crypt foci (ACF) and prostaglandin E 2 production. All drugs significantly enhanced apoptosis and inhibited ACF, irrespective of their COX-inhibiting potency (p<0.01), but sulindac was more potent in inhibition of large ACF, p<0.05. COX-inhibiting sulindac achieved the greatest protective effect. The greater safety profile of Rac-FB should provide an advantage for chemoprevention.
Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers
(Public Library of Science, 2013-05-23) Hu, Ying; McIntosh, Graeme H; Le Leu, Richard Kevin; Nyskohus, Laura S; Woodman, Richard John; Young, Graeme Paul
Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1ppm selenium as selenium-enriched milk protein, or combination of 1ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P,0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P,0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.
Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation
(Springer-Verlag, 2013-08-29) Le Leu, Richard Kevin; Young, Graeme Paul; Hu, Ying; Winter, Jean; Conlon, Michael A
Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease. Aims The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis. Methods Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR. Results Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes. Conclusions A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.
Self-reported bowel screening rates in older Australians and the implications for public health screening programs.
(Australasian Medical Journal, 2013-08-31) Zajac, Ian; Flight, Ingrid; Turnbull, Deborah; Young, Graeme Paul; Cole, Stephen Russell; Wilson, Carlene J
BACKGROUND: This paper sought to determine the status of older Australians with regard to Bowel Cancer screening practices occurring outside of the National Bowel Cancer Screening Program. METHOD: A random sample of N=25,511 urban Australians aged 50 to 74 years received a questionnaire via mail asking questions relating to bowel screening. N=8,762 (34.3%) returned a completed questionnaire. RESULTS: Approximately 33% (N=2863) of respondents indicated they had undergone colonoscopy in the preceding five years and 21% (N=1840) had used a Faecal Occult Blood Test (FOBT) in the preceding 12 months. Furthermore, 27% (N=497) of those who had completed an FOBT had also undergone colonoscopy. CONCLUSION: A significant proportion of older Australians might be participating in bowel screening practices outside of the national program (NBCSP). Moreover, the proportion of individuals reporting use of both FOBT and endoscopic services is much higher than the positivity rate of FOBT. Large population FOBT screening programs, such as the NBCSP, that do not consider participation in screening external to the program may underestimate true population screening rates.
Ambivalence and its influence on participation and non-participation in screening for colorectal cancer
(SAGE, 2013-09) Oster, Candice; Zajac, Ian; Flight, Ingrid; Hart, Elizabeth; Turnbull, Deborah; Wilson, Carlene J; Young, Graeme Paul
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and an ideal target for early detection and prevention through cancer screening. Unfortunately, rates of participation in screening are less than adequate. In this article we explore why people who were offered a fecal immunochemical test for CRC decided to participate or not, and for those who did participate, what influenced them to take action and complete the test. We conducted four focus groups and 30 telephone interviews with 63 people. The main reason people decided to screen was “wanting to know” their CRC status, which operated on a continuum ranging from wanting to know, through varying degrees of ambivalence, to not wanting to know. The majority of participants expressed ambivalence about CRC screening, and the main cue to action was the opportunity to screen without being too inconvenienced.

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