CLEAR Study collaborators meeting December 2013
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CLEAR Study collaborators meeting December 2013

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  • Reproductive history and hormone exposureAge at menarche and menopauseUse of hormonal contraceptives and menopausal hormone therapiesNumber of births and miscarriagesAge at first birth and breastfeedingUse of natural and bioidentical hormones
  • The role for sun exposure as a risk factor for cancer risk came about since the proposal of the vitamin D hypothesis, some 30 years ago.It was proposed that Vtamin D deficiency can be a risk factor for various internal cancers namely breast and colon cancers. He based his evidence on ecological data showing increasing cancer risk with increasing latitude. Using latitude as a surrogate for UV, and solar UV exposure is the major source of our vitamin D production, he naturally attributed this effect to serum vitamin D levels.
  • The role of UV-induced immune suppression in skin cancer development is well documented.There is evidence showing induction of lymphoid malignancies, mainly in the spleen and liver, in genetically-modified mice exposed to solar-simulated UV suggesting thatUV-induced immune suppression might increase cancer risk at body sites distant from the site of UV exposure.While the evidence remains weak, there is also a possibility that prostate cancer is caused by an infectious agent, which might promote cancer development in the presence of UV-induced immune suppression, particularly when vitamin D activity is not increasing to counteract the effect of additional UV exposureAnd we therefore proposed Immune suppression as a possible mechanism whereby higher levels of solar UV exposure might increase prostate cancer risk.

CLEAR Study collaborators meeting December 2013 CLEAR Study collaborators meeting December 2013 Presentation Transcript

  • The NSW CLEAR Study Potential Collaborator Meetings, December 4th & 5th, 2013 Investigators: Freddy Sitas, CCNSW Dianne O‟Connell, CCNSW Emily Banks, ANU Michael Barton, UNSW Karen Canfell, UNSW
  • Contents • • • • • • CLEAR Study Overview - Slides 2 to 17 Smoking/Tobacco Use - Slides 18 to 27 Hormones - Slides 28 to 41 Sun Exposure/Sleep - Slides 42 to 55 BMI Exercise & Alcohol - Slides 56 to 70 Infections - Slides 71 to 86
  • CLEAR Study Overview The NSW CLEAR Study Collaborator Meeting Day 1 Thursday December 5th, 2013
  • The NSW CLEAR Study Overview and Methodology Provenance • University of Oxford: – Johannesburg Cancer Case Control Study. Professor Valerie Beral • University of Oxford / Peking Union Medical College: – Million Deaths study. Professors Richard Peto, Bo-Qi Liu (spouse control) • Share some questions with 45 and Up study
  • The NSW CLEAR Study Overview and Methodology CLEAR Study Aims 1. To investigate the molecular and environmental risk factors for cancer in NSW 2. Understand the relative importance of leading / emerging risk factors for cancer in a local setting 3. (Future) Construct a „cancer cohort‟ study to investigate the consequences of a cancer diagnosis 4. Develop a research platform between epidemiologists, basic scientists and clinicians
  • The NSW CLEAR Study Overview and Methodology CLEAR Study Operations Participation – Consent – Questionnaire – +/- blood sample Recruitment − Targeted − Non-targeted Eligibility criteria − Incident cases − NSW resident − > 18 years
  • The NSW CLEAR Study Overview and Methodology Case and Control Design Male Case Female Partner Female Case Male Partner
  • The NSW CLEAR Study Overview and Methodology A Good Control Group • Representative of the background population (if the cases are so) • Comes from the same catchment area as the case • Would use the same hospital if they became a case 1Breslow and Day, Rothman, Schlesselman, Miettinen
  • The NSW CLEAR Study Overview and Methodology Recruitment Sites of Participants Port Macquarie Hospital 2% Royal Prince Alfred Hospital 2% Liverpool Hospital 3% HCF Health Fund Registry 4% St Vincents Hospital 2% Other 7% Riverina Cancer Care Centre 6% SESIAHS ClinCR 41% Cancer Council NSW 9% SSWAHS ClinCR 24%
  • The NSW CLEAR Study Overview and Methodology Actual Numbers (see Data book, page 5) Note: Cancer types with less than N=20 are grouped under the Other category
  • The NSW CLEAR Study Overview and Methodology Illustrative Numbers of Cancer Patients (18-79 years) • • • Now: Link to NSW Central Cancer Registry – Diagnosis, topography morphology and staging Future: – Deaths, Event and COD, [RBDM, ABS] – Admitted Patient Data Collection – Pathology records (negotiating) – Dental records – Medicare (negotiating) [MBS, PBS]
  • The NSW CLEAR Study Biobank Collection Protocol ACD Plasma ACD Buffy coat Serum ACD - RT SST - ~4⁰C -80⁰C Process ≤48hrs
  • The NSW CLEAR Study Protocol Compliance Samples received (n) 4500 82% 4000 3500 3000 2500 QUALITY REPORTING • Delivery temperature • Date/Time of collection • Date/Time of processing • Haemolysis score • Short fill 2000 1500 1000 500 0 0 1 2 3 Days 4 5 6 7 >7
  • The NSW CLEAR Study Biospecimen Quality Control CCNSW Stability Study • pre-analytic variation (t and time) • 4 vacutainer types • several molecular groups eg; antibodies, cytokines, ncRNAs Further enquiries: verityh@nswcc.org.au
  • The NSW CLEAR Study Application Process Online Application Data Access Coordinator (practical feasibility check) Expert Advisory Committee (EAC) (peer review of all aspects of application) Y/N CLEAR Principal Investigator Feedback to Applicant
  • The NSW CLEAR Study Cost Structure • Application Fee: $500 • Licence Fee: $20,000 • Linked data - additional fee: $3,000 • Preparation for linkage: $3,000 • Data cleaning: $100 per hour
  • The NSW CLEAR Study Cost Structure Application Fee: $500.00 Plasma and Serum: $20 per 500µl aliquot DNA: $47.50 per 25 µl aliquot Licence Fee applies if variables beyond minimum data set are requested Timing of release of aliquots may be dependent on quantities requested and on other applications for the same product.
  • Smoking and Tobacco The NSW CLEAR Study Collaborator Meeting Day 1 Thursday December 5th, 2013
  • The NSW CLEAR Study Smoking / Tobacco Questions
  • The NSW CLEAR Study Frequency of Cancer Types
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Our current work on Smoking/Tob. Australia • No contemporary studies of risk of smoking • All estimates indirect −Underestimate?
  • The NSW CLEAR Study Our current work on Smoking/Tob. The importance of local studies Relative risk of developing lung cancer (US Smoker vs. non-smoker) Year of study M F 1959-1965 12 3 1982-1988 25 13 2000-2010 27 26
  • The NSW CLEAR Study Our current work on Smoking/Tob. Research Questions 1. Contemporary risks of smoking on cancer in Australia 2. Add to evidence where causation is inconclusive • Bowel (IARC 100th Mono) • Prostate • Breast
  • The NSW CLEAR Study Our current work on Smoking/Tob. Cancer type Study Variable OR (95% CI) Women Million Women Study*** 1.0 5.1 20.9 (12.0, 36.3) 31.7 (14.9, 67.7) Never 1.0 1.0 Past 8.1 Current†† Cancer Prevention Study** 1.0 Current† CLEAR* Never Past Lung cancer Men 23.4 (19.6, 25.6) Never 1.0 (3.1, 8.3) (7.2, 9.1) Past Current 21.4 (19.7, 23.2) * adjusted for age, socioeconomic status and migrant status ** adjusted for cohort, age, race and education level ***adjusted for recruitment site, age, body mass index, socioeconomic status, current alcohol intake, physical activity, oral contraceptive use, menopausal status and hormone therapy use. † current smokers are classified as those who still smoke or those who had quit smoking within the previous five years from date of recruitment into study † † current smokers are classified as those who were still smoking at time of recruitment into study 5.8 7.1 (2.9, 11.7) (6.1, 8.2) 25.6 (21.7, 30.3)
  • The NSW CLEAR Study Our current work on Smoking/Tob. Cancer type Study Variable OR (95% CI) Women 1.0 1.4 (1.0, 2.1) 1.4 (1.0, 1.9) Current† 2.2 (1.5, 3.4) 4.9 (3.5, 7.0) Never 1.0 1.4 (1.1, 1.8) 2.8 (2.2, 3.5) Current† JCCC**** 1.0 Past CLEAR* Never Past Tobacco related cancers Men 1.9 (1.6, 2.2) 4.6 (3.7, 5.7) •adjusted for age, socioeconomic status and migrant status •**** adjusted for age, education, smoking status and cooking fuel † current smokers are classified as those who still smoke or those who had quit smoking within the previous five years from date of recruitment into study 1.0
  • The NSW CLEAR Study Our current work on Smoking/Tob. A Typical Analysis (e.g. Stein et al 2008)
  • Hormones The NSW CLEAR Study Collaborator Meeting Day 1 Wednesday December 4th, 2013
  • The NSW CLEAR Study Hormones Questions Hormone Exposure in Women
  • The NSW CLEAR Study Hormones Questions Hormone Exposure in Women (Cont’d)
  • The NSW CLEAR Study Hormones Questions Other related information captured in CLEAR • Family history of breast and ovarian cancers • Hysterectomy , oophorectomy, sterilisation and pregnancy terminations • Breast screening mammograms and Pap smear test histories
  • The NSW CLEAR Study Hormones Questions Hormone Exposure in Men
  • The NSW CLEAR Study Frequency of Cancer Types
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Our current work on Hormones Hormones and Breast cancer risk Case-control analyses using data from the NSW CLEAR study PhD candidate – Usha Salagame Supervisors – A/Prof Karen Canfell A/Prof Freddy Sitas Prof Emily Banks
  • The NSW CLEAR Study Our current work on Hormones Research Objectives Estimating the risk associated with specific exposures and comparing them with results from large collaborative studies to validate the study design and use of spouse controls • • • • • • • • Age at menarche Abortion Age at first birth Use of oral contraceptives Breast feeding Menopausal status Parity Family history
  • The NSW CLEAR Study Our current work on Hormones Research Objectives Cont‟d Case-control analysis- MHT use and breast cancer risk Analysis by • current, past and ever use of MHT • by duration of use • type of MHT preparation
  • The NSW CLEAR Study Our current work on Hormones Why study MHT use and its association to breast cancer? • Increased risk of breast cancer due to menopausal hormone therapy -established elsewhere in the world1,2. • An estimation of the risks specifically in NSW among Australian women through CLEAR study -contemporary and local. • Prior work suggests that much of the drop in breast cancer incidence rates is due to the concurrent decline in HRT prescriptions in Australia3. 1.Writing group for the Women's Health Initiative investigators. Risks and benefits of estrogen plus progestin in healthy menopausal women: principal results from the Women's Health Initiative randomised controlled trial. JAMA 2002; 288: 321-33. 2.Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003; 362:419-27. 3.Karen Canfell, Emily Banks, Aye M Moa and Valerie Beral. Decrease in breast cancer incidence following a rapid fall in use of hormone replacement therapy in Australia.MJA 2008; 188:641-44.
  • The NSW CLEAR Study Our current work on Hormones Example of analysis: The Million Women Study 2003
  • Sun Exposure and Sleep The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
  • The NSW CLEAR Study Sun Exposure and Sensitivity Questions Outdoor UV Exposure
  • The NSW CLEAR Study UV Exposure and Sleep Questions Indoor UV Exposure Sleep
  • The NSW CLEAR Study Sun exposure and cancer risk Sun Exposure and Internal Cancer Risk Vitamin D hypothesis -vitamin D deficiency may be a risk factor for cancer.
  • The NSW CLEAR Study Current evidence Vitamin D and cancer risk - Health Professionals Study (USA) 2006
  • The NSW CLEAR Study Current evidence Sun exposure and cancer risk: NIH-AARP Diet and Health Study (2012)
  • The NSW CLEAR Study Current evidence- NSW Sun exposure and prostate cancer in NSW: Prostate Cancer Care and Outcomes -Sun Study (2012) Table 1. Odds ratios for prostate cancer in quartiles of increasing weekly hours of sun exposure Odds ratio1 (95% CI) Solar UV exposure (Quartiles) Q1 Q2 Q3 Q4 p-value4 1Adjusted Weekly 1.00 1.3 (0.9,1.9) 1.5 (1.0,2.2) 2.1 (1.4,3.2) 0.007 for year of birth and sun sensitivity. Weekend 1.00 1.4 (0.9,2.0) 1.6 (1.1,2.3) 5.6 (2.9,10.5) <0.0001
  • The NSW CLEAR Study Systematic review Sun exposure, vitamin D and cancer risk (De Vries 2013) • Almost all epidemiological studies suggest that sun exposure is linked with risk of colorectal, breast, prostate, NHL cancers • No associations between vitamin D and cancers of the prostate and NHL. • Prostate and NHL “other sunlight potentiated and vitamin D independent pathways i.e. immune modulation and circadian rhythm and folic degradation may play a role”.
  • The NSW CLEAR Study Sleep and cancer risk Circadian Rhythm and Cancer Risk "shift-work that involves circadian disruption" as "probably carcinogenic to humans" (Group 2A) - The International Agency for Research on Cancer
  • The NSW CLEAR Study Evidence on sleep and cancer risk Meta-analysis of the association between long sleep and risk of cancer: Prospective Cohort Studies (Lu et al 2013)
  • The NSW CLEAR Study Our current work on Sun Exp/Sleep Sun exposure and cancer link in CLEAR • Time spent outdoors
  • The NSW CLEAR Study Frequency of Exposures • • • • Places lived Solarium use Duration of sleep Shift work
  • The NSW CLEAR Study Frequency of Cancer Types
  • BMI / Physical Activity Alcohol The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
  • The NSW CLEAR Study BMI/Physical Activity Questions Similar Q in 45+
  • The NSW CLEAR Study BMI/Physical Activity Questions
  • CLEAR Study – BMI questions
  • The NSW CLEAR Study Alcohol Questions
  • The NSW CLEAR Study Frequency of Cancer Types
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study BMI/Phys Act Research Questions • Which cancers are associated with BMI in Australia • Are there differences – between M&F – Migrant groups – BMI at different ages – Pre and post-menopausal?
  • The NSW CLEAR Study BMI/Phys Act Possible analyses using CLEAR (Reeves et al, MWS 2008)
  • The NSW CLEAR Study Alcohol Alcohol Smoking Comment - - Baseline – Methodological problems of ascertaining former vs. never drinkers. Use co-morbidities as proxy? + - Studies limited by statistical power. InterSCOPE shows some associations + Adj or not sp. Association well established for numerous cancer types + + Strong, consistent association – multiplicative
  • The NSW CLEAR Study Current work on Alcohol: InterSCOPE, n=4000
  • The NSW CLEAR Study Alcohol • Which cancers are associated with alcohol – Upper digestive, bowel, breast, … • Interactions? With BMI, Smoking • Alcohol dehydrogenase ($)
  • Infectious Diseases The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
  • The NSW CLEAR Study Infectious Diseases Questions Lifestyle related questions
  • The NSW CLEAR Study Infectious Diseases Questions Tattoos and Peircings IV Drug Use
  • The NSW CLEAR Study Infectious Diseases Questions Blood Transfusion Organ Transplant
  • The NSW CLEAR Study Frequency of Cancer Types
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Frequency of Exposures
  • The NSW CLEAR Study Our current work on Infect. Dis. Research Opportunities • Number of cancers caused by known infections in Australia is small ~3% • Still cause significant mortality and morbidity • Infections can be removed • Infectious disease discovery not over yet − Bladder, H&N, Prostate?, haematological, [skin] … o Spinoffs: diagnostics, blood supply, vaccine, chemotherapy • Add other studies that can increase sample sizes
  • The NSW CLEAR Study Our current work on Infect. Dis. Research Questions • Questionnaire correlates – Are specific lifestyle factors correlated with specific cancers? • Sex behaviour • Tattoos • Piercings • IV drugs • Prostatitis • Blood transfusion • Organ transplant
  • The NSW CLEAR Study Our current work on Infect. Dis. Research Questions • Pathogen-related screening tools developed for – cervical cancer (HPV screening) – liver cancer (hepatitis B, C) • No screening tools for – H&N, male genital, stomach, … • Suspected infectious cause for several cancers yet to be unravelled
  • The NSW CLEAR Study Our current work on Infect. Dis. List of Pathogens – DKFZ ~100 • HPV1-107 • L1, E2, E6, E7 • SV40 • Polyoma BK, JV, MC • H.pylori 21 proteins • Hepatitis B, C • Herpes I,II, CMV, EBV • Retroviruses • Luminex platform • Several under construction • High throughput • ~AU$15 per sample, 50 results • 0.2ml serum
  • The NSW CLEAR Study Our current work on Infect. Dis. Types of Research Questions • Serotype distribution of HPV in background (controls) and in cases of H&N, cervix, other genital sites (n?) • Improving predictive value of serological markers • Existing pathogen, new disease • New pathogen?
  • The NSW CLEAR Study Our current work on Infect. Dis. Illustration of Results – New Pathogen e.g. Sitas 1999 1. 2. 3. 4. How common? How dangerous? Which cancers? Which cancers NOT?
  • The NSW CLEAR Study Our current work on Infect. Dis. Many pathogens, one cancer: InterSCOPE: HPV serological markers and OSCC