Renehan opac2013

1,310 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,310
On SlideShare
0
From Embeds
0
Number of Embeds
819
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Renehan opac2013

  1. 1. IASO/WCRF Meeting, London 17th April 2013Energy balance, adiposity, physicalactivity, and colorectal cancer: clinicalperspectivesAndrew G Renehan PhD FRCS FRCS(GenSurg)Department of Surgery, The Christie NHS Foundation TrustMRC Health eResearch CentreFaculty Institute of Cancer Sciences, University of ManchesterManchester Academic Health Science Centre
  2. 2. “There are known knowns;there are things we know that we know.There are known unknowns; that is to say there arethings that, we now know we dont know.But there are also unknown unknowns – there arethings we do not know, we dont know.”US Secretary of Defense, Donald Rumsfeld, 2002Message no. 1
  3. 3. Message no. 2Influences of BMI:pre-diagnosis ≠ post-diagnosis
  4. 4. Message no. 3Will Rogers phenomenon“When the Okies left Oklahoma and went toCalifornia, the average intelligence of bothstates went up”Tumour stage migration
  5. 5. W-R phenomenon: effect on survivalPatients with anal cancer undergoing chemo-radiotherapyChristie Hospital 1988-20110.000.250.500.751.00Survival(%)0 12 24 36 48 60Time in months1988 to 2003, N = 190Cancer-specific survivalNode negativeNode positiveP = 0.002n = 156n = 34 (18%)0 12 24 36 48 60Time in monthsNode negative2004 to 2011, N = 206Cancer-specific survival0.000.250.500.751.00Node positiveP = 0.576n = 137n = 69 (34%)Pre-treatmentMR staging
  6. 6. Obesity & colorectal cancer risk
  7. 7. BMI and cancer riskRenehan et al. Lancet 371; 569-578: 2008
  8. 8. By colorectal site & gender21171.24 (1.20, 1.28)1.09 (1.05, 1.12)No. ofstudies RR (95% CI)RR (95% CI)ColonRectumMENRisk ratio(per 5 kg/m2 increase)ColonRectum15111.09 (1.04, 1.14)1.01 (0.99, 1.04)WOMEN10.8 1 1.5Harriss on behalf of C-CLEARColorectal Dis 2009; 11:547-63.P < 0.0001P < 0.0001
  9. 9. Implications of gender & site specificity• Specificity – Bradford-Hill criteria of causality• Biological implications- gender-specific physiology- site-specific molecular characteristicsHucthins .... QuirkeJCO 2011
  10. 10. MS-stable MSI-low MSI-highn 913/1376 149/230 188/274OR (95% CIs)per 5 kg/m21.38(1.24-1.54)1.33(1.04-1.72)1.05(0.94-1.31)
  11. 11. Weight gain in adulthood
  12. 12. • 500,000 men & women• baseline age: 63.1 years• baseline collection: 1995 to 1996• followed to 2007 (last update)• detailed lifestyle & dietary cohort• retrospective questionnaire: 18y; 35y; 50y
  13. 13. Weight gain in adulthoodRenehan et al.Am J Epi 20120.50.8123Relativerisk[logscale]-1 -.5 0 .5 1 1.5 2Weight gain 18 to 62 yr)Colon cancer risk in menper0.5 kg/y0.50.8123Relativerisk[logscale]-1 -.5 0 .5 1 1.5 2weight gain [kg/year]Weight gain 18 to 35 yrper0.5 kg/y
  14. 14. WC/ WHR & colorectal cancer riskAbdominal adiposity may better reflect metabolic dysfunction
  15. 15. Issues: WC/WHR versus BMI is:1. Stronger associations for cancer risk2. WC ‘independent’ effect from BMI:2.1 Adjustment for BMI residual WC effect2.2 WC ‘independent’ effects within each BMI category3. WC as a better ‘discriminator’ of risk that BMI4. Different WC v BMI patterns of association by ethnic groupsAdapted from Huxley et al. Eur J ClinNutr 2010: 64:16-22Considerations
  16. 16. Men WomenCohort 129,731 238,546age 52.8 51.1Colon cancers 421 563BMI (Q5 v Q1) 1.55(1.12-2.15)1.06(0.79-1.42)WC (Q5 v Q1) 1.39(1.01-1.93)1.48(1.08-2.03)WHR (Q5 v Q1) 1.51(1.06-2.15)1.52(1.12-2.05)Colon cancer risk: mean FU = 6.1 y
  17. 17. Waist circumference ≠ visceral adiposity65yr MWC = 111 cmBMI = 32.6 kg/m2SAT vol = 2291 cm3VAT vol = 3049 cm356yr FWC = 111 cmBMI = 29.8 kg/m2SAT vol =2904 cm3VAT vol = 918 cm3WCWC
  18. 18. BMI, WC & WHR in the AARP cohortKeimling, Renehan ......... Leitzmann submittedMen WomenCohort 124,261 79,220age 63.3 62.9Colon cancers 1471 683BMI (per SD) 1.14(1.08-1.20)0.97(0.90-1.06)WC (per SD) 1.17(1.08-1.26)0.98(0.87-1.11)WHR (per SD) 1.09(1.04-1.14)1.00(0.92-1.08)Colon cancer risk: mean FU = 9.3 yno differenceP < 0.001
  19. 19. Ni Mhurchu et al IJE 2004(2 kg/m2 reduction in BMI)EPIC v AARP: explanationsAsia Pacific Cohort Studies Collaboration
  20. 20. Summary on cancer risk• Increased BMI is an established risk factor forcolorectal cancer in gender- & site-specific manner• Stronger associations for MS-stable and MSI-lowcolorectal cancer• Weight gain, perhaps in early adulthood, is a riskfactor for colon cancer• WC & WHR are also associated with increasedrisk – whether or not better ‘risk predictor’ is unclear
  21. 21. BMI & cancer mortality & survival
  22. 22. Obesity & cancer mortality/survival: 2 cohort typesInception cohort design/pre-diagnosis (mortality)CohortentryCancerdiagnosis DeathExposureCancerdiagnosisDeathTreatment cohort/Post-diagnosis survivalTreatmentExposure
  23. 23. Baseline BMI & colorectal cancer mortalityCalle et al. NEJM 2003; 348:1625-38
  24. 24. Baseline BMI & colorectal cancer mortalityCalle et al. NEJM 2003; 348:1625-38
  25. 25. Obesity, cancer mortality & survival:pre- & post-diagnosis BMICohortentryCancerdiagnosis DeathBaselineBMIPre-dxBMI (b)Post-dxBMIPre-dxBMI (a)Post-dxBMI(a)Post-dxBMI(b)
  26. 26. Post-diagnosis BMI & breast cancer survivalNiraula..............Goodwin Breast Cancer Res Treat 2012; 5 MayCancer specific survival
  27. 27. Pre-diagnosis BMI & mortalityKuipar (2010)Cancer mortalityCampbell (2012)Campbell (2012)I2 = 0.0%Authors (year)Prizment (2010)Kuipar (2010)All cause mortalityPrizment (2010)I2 = 0.0%USAUSAUSACountryUSAUSAUSAWHICPSIICPSIICohortIWHSWHIIWHSC&RC&RC&RSitecolonC&Rcolon171851380Cases2892654931.17 (0.80, 1.71)1.30 (1.06, 1.59)1.35 (1.01, 1.80)1.33 (1.16, 1.52)RR (95% CI)1.30 (0.94, 1.79)1.19 (0.88, 1.61)1.46 (1.15, 1.86)1.29 (1.07, 1.55)11.9 y16 y FU16 y FUFUup to 20 y11.9 yup to 20 y1.17 (0.80, 1.71)1.30 (1.06, 1.59)1.35 (1.01, 1.80)1.33 (1.16, 1.52)RR (95% CI)1.30 (0.94, 1.79)1.19 (0.88, 1.61)1.46 (1.15, 1.86)1.29 (1.07, 1.55)11.9 y16 y FU16 y FUup to 20 y11.9 yup to 20 y10.8 1 1.5 2RR forobese v normalAnalysis from time of diagnosis“Pre-diagnostic obesity may be a modifiable risk factorfor death in colon cancer patients”
  28. 28. All cause Cancer-specificPre-diagnosis BMI 1.30(1.06-1.59)1.35(1.01-1.80)Post-diagnosis BMI 0.93(0.75-1.17)1.14(0.81-1.60)Mortality: obese versus normal
  29. 29. Will-Rogers phenomenonRenehan, Crosbie, Campbell JNCI letter submittedPre-diagnosisPost-diagnosis DifferenceNo. of patients 2303 1957 346 (15%)Weights in kgAll patients 79.08 77.03 2.05Pre-diagnosis BMI category<18.5 kg/m2 55.13 55.17 -0.0318.5 to 24.9 kg/m2 67.84 66.17 1.6725.0 to 29.9 kg/m2 82.19 80.40 1.7930.0 to 34.9 kg/m2 94.99 90.96 4.0335.0 kg/m2 108.30 103.70 4.60
  30. 30. Will-Rogers phenomenonRectalcancerdiagnosisBanks ............. Renehan unpublished Greater Manchester Rectal Cancer AuditDefinitivemajorsurgeryChemo-radiation(5 wks)10-12wksN =218N =156Total 62(28%)25(33%)26(27%)4(11%)BMI20-25 kg/m2n = 76BMI25-30 kg/m2n = 95BMI>30 kg/m2n = 35BMI< 20 kg/m2n = 127(58%)
  31. 31. “When the Okies left Oklahoma and went toCalifornia, the average intelligence of bothstates went up”Post-diagnosis BMI migrationWill-Rogers phenomenon
  32. 32. BMI & endometrial cancer survival: ASTEC trial0.000.600.700.800.901.00Survival(%)0 12 24 36 48 60Time in monthsOverweightNormal weightObese IIObese IObese IIIType I (oestrogen-sensitive) endometrial cancer, N = 1004Increasing BMI• endometrium only• tumour grade• LV permeation
  33. 33. Post-diagnosis BMI & renal cancer survivalWaalkes et al. Cancer Causes Control 2010; 21:1905-10University Hospital series• N = 1338• Mean FU: 5.1 y• a priori stratificationObese II/IIIObese INormalUnderweight
  34. 34. The ‘Overweight Paradox’Sinicrope et al. Cancer 2013• ACCENT consortium• 21 RCT trials• 5-FU adjuvant chemo• N = 25,291• FU = 7.8 yearsMenHR for DFS:0.94 (0.88-1.00)36% of pop.
  35. 35. Summary on cancer mortality/survival• Associations between excess adiposity andcancer incidence may not directly extrapolate tosame direction associations after diagnosis• Demonstrated ‘time-related biases’ related towhen BMI is measured v cancer outcome• In some cancers, there may be some protectiveeffect of being overweight during treatment – the‘overweight paradox’
  36. 36. AcknowledgementsBern, SwitzerlandProfessor M EggerDr M ZwhalenAarhus, DenmarkProfessor A FlyvbjergProfessor J FrystykRegensburg, GermanyProfessor M LeitzmannDr M KeimlingAmerican Cancer SocietyDr PT CampbellErasmus/IARCProfessor JW CoeberghDr I SoerjomataramManchester (colorectal)Whole teamManchester (others)Professor S ShaletProfessor P ClaytonProfessor A HowellDr M HarvieProfessor G EvansProfessor H KitchenerDr E CrosbieManchester (epidemiology)Professor I BuchanDr E BadrickDr M Carr
  37. 37. Thank you

×