The NSW CLEAR Study
Potential Collaborator Meetings, December 4th & 5th, 2013
Investigators:
Freddy Sitas, CCNSW
Dianne O‟...
Contents
•
•
•
•
•
•

CLEAR Study Overview - Slides 2 to 17
Smoking/Tobacco Use - Slides 18 to 27
Hormones - Slides 28 to ...
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....
The NSW CLEAR Study

Overview and Methodology
CLEAR Study Aims
1. To investigate the molecular and environmental risk
fact...
The NSW CLEAR Study

Overview and Methodology
CLEAR Study Operations

Participation
– Consent
– Questionnaire
– +/- blood ...
The NSW CLEAR Study

Overview and Methodology
Case and Control Design

Male Case

Female Partner

Female Case

Male Partne...
The NSW CLEAR Study

Overview and Methodology
A Good Control Group
• Representative of the background
population (if the c...
The NSW CLEAR Study

Overview and Methodology
Recruitment Sites of Participants
Port Macquarie
Hospital
2%

Royal Prince A...
The NSW CLEAR Study

Overview and Methodology
Actual Numbers (see Data book, page 5)

Note: Cancer types with less than
N=...
The NSW CLEAR Study

Overview and Methodology
Illustrative Numbers of Cancer Patients (18-79 years)
•
•
•

Now:
Link to NS...
The NSW CLEAR Study

Biobank Collection Protocol
ACD Plasma
ACD Buffy coat
Serum

ACD - RT
SST - ~4⁰C

-80⁰C

Process
≤48h...
The NSW CLEAR Study

Protocol Compliance
Samples received (n)

4500

82%

4000
3500
3000
2500

QUALITY REPORTING
• Deliver...
The NSW CLEAR Study

Biospecimen Quality Control
CCNSW Stability Study
• pre-analytic variation (t and time)
• 4 vacutaine...
The NSW CLEAR Study

Application Process
Online Application
Data Access Coordinator
(practical feasibility check)

Expert ...
The NSW CLEAR Study

Cost Structure
• Application Fee: $500
• Licence Fee: $20,000
• Linked data - additional fee: $3,000
...
The NSW CLEAR Study

Cost Structure
Application Fee: $500.00
Plasma and Serum: $20 per 500µl aliquot
DNA: $47.50 per 25 µl...
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 estimat...
The NSW CLEAR Study

Our current work on Smoking/Tob.
The importance of local studies

Relative risk of developing lung ca...
The NSW CLEAR Study

Our current work on Smoking/Tob.
Research Questions

1. Contemporary risks of smoking on
cancer in Au...
The NSW CLEAR Study

Our current work on Smoking/Tob.
Cancer type

Study

Variable

OR (95% CI)
Women

Million Women
Study...
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)...
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 ovaria...
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
th...
The NSW CLEAR Study

Our current work on Hormones
Research Objectives
Estimating the risk associated with specific exposur...
The NSW CLEAR Study

Our current work on Hormones
Research Objectives Cont‟d
Case-control analysis- MHT use and breast can...
The NSW CLEAR Study

Our current work on Hormones
Why study MHT use and its
association to breast cancer?
• Increased risk...
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 d...
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...
The NSW CLEAR Study

Systematic review
Sun exposure, vitamin D and cancer risk (De Vries 2013)
• Almost all epidemiologica...
The NSW CLEAR Study

Sleep and cancer risk
Circadian Rhythm and Cancer Risk
"shift-work that involves circadian disruption...
The NSW CLEAR Study

Evidence on sleep and cancer risk
Meta-analysis of the association between long sleep and risk of
can...
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 dif...
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...
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, …
• Interaction...
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 infection...
The NSW CLEAR Study

Our current work on Infect. Dis.
Research Questions
• Questionnaire correlates
– Are specific lifesty...
The NSW CLEAR Study

Our current work on Infect. Dis.
Research Questions

• Pathogen-related screening tools developed for...
The NSW CLEAR Study

Our current work on Infect. Dis.
List of Pathogens – DKFZ ~100

• HPV1-107
• L1, E2, E6, E7
• SV40
• ...
The NSW CLEAR Study

Our current work on Infect. Dis.
Types of Research Questions

• Serotype distribution of HPV in
backg...
The NSW CLEAR Study

Our current work on Infect. Dis.
Illustration of Results – New Pathogen e.g. Sitas 1999
1.
2.
3.
4.

...
The NSW CLEAR Study

Our current work on Infect. Dis.
Many pathogens, one cancer: InterSCOPE: HPV
serological markers and ...
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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

    1. 1. 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
    2. 2. 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
    3. 3. CLEAR Study Overview The NSW CLEAR Study Collaborator Meeting Day 1 Thursday December 5th, 2013
    4. 4. 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
    5. 5. 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
    6. 6. 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
    7. 7. The NSW CLEAR Study Overview and Methodology Case and Control Design Male Case Female Partner Female Case Male Partner
    8. 8. 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
    9. 9. 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%
    10. 10. 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
    11. 11. 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]
    12. 12. The NSW CLEAR Study Biobank Collection Protocol ACD Plasma ACD Buffy coat Serum ACD - RT SST - ~4⁰C -80⁰C Process ≤48hrs
    13. 13. 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
    14. 14. 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
    15. 15. 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
    16. 16. 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
    17. 17. 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.
    18. 18. Smoking and Tobacco The NSW CLEAR Study Collaborator Meeting Day 1 Thursday December 5th, 2013
    19. 19. The NSW CLEAR Study Smoking / Tobacco Questions
    20. 20. The NSW CLEAR Study Frequency of Cancer Types
    21. 21. The NSW CLEAR Study Frequency of Exposures
    22. 22. The NSW CLEAR Study Our current work on Smoking/Tob. Australia • No contemporary studies of risk of smoking • All estimates indirect −Underestimate?
    23. 23. 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
    24. 24. 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
    25. 25. 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)
    26. 26. 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
    27. 27. The NSW CLEAR Study Our current work on Smoking/Tob. A Typical Analysis (e.g. Stein et al 2008)
    28. 28. Hormones The NSW CLEAR Study Collaborator Meeting Day 1 Wednesday December 4th, 2013
    29. 29. The NSW CLEAR Study Hormones Questions Hormone Exposure in Women
    30. 30. The NSW CLEAR Study Hormones Questions Hormone Exposure in Women (Cont’d)
    31. 31. 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
    32. 32. The NSW CLEAR Study Hormones Questions Hormone Exposure in Men
    33. 33. The NSW CLEAR Study Frequency of Cancer Types
    34. 34. The NSW CLEAR Study Frequency of Exposures
    35. 35. The NSW CLEAR Study Frequency of Exposures
    36. 36. 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
    37. 37. 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
    38. 38. 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
    39. 39. 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.
    40. 40. The NSW CLEAR Study Our current work on Hormones Example of analysis: The Million Women Study 2003
    41. 41. Sun Exposure and Sleep The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
    42. 42. The NSW CLEAR Study Sun Exposure and Sensitivity Questions Outdoor UV Exposure
    43. 43. The NSW CLEAR Study UV Exposure and Sleep Questions Indoor UV Exposure Sleep
    44. 44. 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.
    45. 45. The NSW CLEAR Study Current evidence Vitamin D and cancer risk - Health Professionals Study (USA) 2006
    46. 46. The NSW CLEAR Study Current evidence Sun exposure and cancer risk: NIH-AARP Diet and Health Study (2012)
    47. 47. 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
    48. 48. 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”.
    49. 49. 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
    50. 50. 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)
    51. 51. The NSW CLEAR Study Our current work on Sun Exp/Sleep Sun exposure and cancer link in CLEAR • Time spent outdoors
    52. 52. The NSW CLEAR Study Frequency of Exposures • • • • Places lived Solarium use Duration of sleep Shift work
    53. 53. The NSW CLEAR Study Frequency of Cancer Types
    54. 54. BMI / Physical Activity Alcohol The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
    55. 55. The NSW CLEAR Study BMI/Physical Activity Questions Similar Q in 45+
    56. 56. The NSW CLEAR Study BMI/Physical Activity Questions
    57. 57. CLEAR Study – BMI questions
    58. 58. The NSW CLEAR Study Alcohol Questions
    59. 59. The NSW CLEAR Study Frequency of Cancer Types
    60. 60. The NSW CLEAR Study Frequency of Exposures
    61. 61. The NSW CLEAR Study Frequency of Exposures
    62. 62. The NSW CLEAR Study Frequency of Exposures
    63. 63. The NSW CLEAR Study Frequency of Exposures
    64. 64. 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?
    65. 65. The NSW CLEAR Study BMI/Phys Act Possible analyses using CLEAR (Reeves et al, MWS 2008)
    66. 66. 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
    67. 67. The NSW CLEAR Study Current work on Alcohol: InterSCOPE, n=4000
    68. 68. The NSW CLEAR Study Alcohol • Which cancers are associated with alcohol – Upper digestive, bowel, breast, … • Interactions? With BMI, Smoking • Alcohol dehydrogenase ($)
    69. 69. Infectious Diseases The NSW CLEAR Study Collaborator Meeting Day 2 Thursday December 5ht, 2013
    70. 70. The NSW CLEAR Study Infectious Diseases Questions Lifestyle related questions
    71. 71. The NSW CLEAR Study Infectious Diseases Questions Tattoos and Peircings IV Drug Use
    72. 72. The NSW CLEAR Study Infectious Diseases Questions Blood Transfusion Organ Transplant
    73. 73. The NSW CLEAR Study Frequency of Cancer Types
    74. 74. The NSW CLEAR Study Frequency of Exposures
    75. 75. The NSW CLEAR Study Frequency of Exposures
    76. 76. 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
    77. 77. 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
    78. 78. 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
    79. 79. 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
    80. 80. 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?
    81. 81. 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?
    82. 82. The NSW CLEAR Study Our current work on Infect. Dis. Many pathogens, one cancer: InterSCOPE: HPV serological markers and OSCC
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