Weight change and Upper-aerodigestive tract (UADT) Cancers › epi › faculty › zhang › courses...

Body mass index (BMI), change in BMI Body mass index (BMI), change in BMI and cancers of the and cancers of the endometriumendometrium, ,

upperupper--aerodigestiveaerodigestive tract (UADT), and lungtract (UADT), and lung

S. Lani ParkS. Lani ParkOctober 9, 2009October 9, 2009

Presentation OutlinePresentation Outline

Overview of body weight and cancerOverview of body weight and cancerEndometrial cancerEndometrial cancerUADT cancerUADT cancerLung and UADT cancerLung and UADT cancer

With the increasing obesity epidemicWith the increasing obesity epidemic……

RenehanRenehan, 2008, 2008

Obesity and Cancer Obesity and Cancer biomechanismbiomechanism

Calle EE, Kaaks R. Nature, 2004

van van KruijsdijkKruijsdijk RCM C, CEBP, 2009RCM C, CEBP, 2009

Potential pathways Potential pathways linking obesity with linking obesity with cancercancer

Markers for adiposityMarkers for adiposity

Weight: adulthood weight gain (age 18 to Weight: adulthood weight gain (age 18 to 55) usually reflects an increase in body fat.55) usually reflects an increase in body fat.BMI (kg/mBMI (kg/m22): highly correlated with both ): highly correlated with both absolute body fat and percent body fat. absolute body fat and percent body fat. –– WHO categories: WHO categories:

Normal: 18.5Normal: 18.5--24.9 kg/m24.9 kg/m22

Moderate: 25Moderate: 25--29.9 kg/m29.9 kg/m22

Obese: Obese: ≥≥ 30 kg/m30 kg/m22

WaistWaist--HipHip--Ratio: measure for central Ratio: measure for central adiposityadiposity

Things to consider when Things to consider when studying BMI in cancerstudying BMI in cancer

Reverse causalityReverse causalityConfounding variablesConfounding variablesEthnic differencesEthnic differencesSelf report validity, information biasSelf report validity, information bias

Validity of selfValidity of self--reported height and weightreported height and weight

Hu FB, Obesity Epidemiology

Statistical ModelsStatistical Models Hu FB, Obesity Epidemiology

Factors affecting body weightFactors affecting body weight

GeneticGeneticEndocrine/regulatoryEndocrine/regulatoryBehavioralBehavioralPsychosocialPsychosocialEnvironmentalEnvironmental

Factors to consider when Factors to consider when investigating body weight changeinvestigating body weight change

Reverse causalityReverse causalityConfounding Confounding variablesvariablesEthnic differencesEthnic differencesSelf report validity, Self report validity, information biasinformation biasEnergy BalanceEnergy Balance–– Food consumptionFood consumption–– Physical ActivityPhysical Activity

CollinearityCollinearity

Energy Balance Energy Balance The balance between energy taken in, The balance between energy taken in, generally by food and drink, and energy generally by food and drink, and energy expended. expended. Energy expenditure is influenced by genetics, Energy expenditure is influenced by genetics, body size and amount of muscle, and by body size and amount of muscle, and by physical activity. physical activity. While calories are probably the most critical While calories are probably the most critical element in maintaining your energy balance, element in maintaining your energy balance, other factors in your diet such as how much other factors in your diet such as how much fiber or calcium you eat may influence your fiber or calcium you eat may influence your energy expenditure and how much muscle energy expenditure and how much muscle and fat you have. and fat you have.

Vaughn P, www.cancer.gov

Example of SemiExample of Semi--quantitative FFQquantitative FFQDIETARY HABITS [Example, will need to adapt to each country] How often did you consume the following foods and beverages one year ago?

UnitUnit Food item Food item How many times per day, week, month, How many times per day, week, month, year? (mark one column only)year? (mark one column only)

dayday weekweek monthmonth yearyear NeverNeverD1D1 1 portion1 portion BeefBeef |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D2D2 1 portion 1 portion PorkPork |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D3D3 1 portion 1 portion PoultryPoultry |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D4D4 1 portion 1 portion Other meat (lamb, etc.)Other meat (lamb, etc.) |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D5D5 1 portion1 portion FishFish |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D6D6 1 portion1 portion Ham, salami, sausagesHam, salami, sausages |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D7D7 1 portion 1 portion Raw green vegetables and Raw green vegetables and

saladssalads|__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D8D8 1 portion1 portion Cooked green vegetablesCooked green vegetables |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D9D9 1 portion1 portion CarrotsCarrots |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D10D10 1 portion1 portion Fresh tomatoesFresh tomatoes |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|D11D11 1 portion1 portion Pulses (peas, beans, etc.)Pulses (peas, beans, etc.) |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

Example of a quantitative FFQExample of a quantitative FFQ

Physical ActivityPhysical Activity

metabolic equivalents of energy expenditure (metabolic equivalents of energy expenditure (METsMETs) ) METsMETs= (sleeping [= (sleeping [h/dh/d]*0.91 + sitting []*0.91 + sitting [h/dh/d]*1.0+ light activity ]*1.0+ light activity [[h/dh/d]*2.4 + moderate activity []*2.4 + moderate activity [h/dh/d]*4.0 + vigorous activity ]*4.0 + vigorous activity [[h/dh/d]*7.2)/24) ]*7.2)/24)

Different measures of body Different measures of body weight change and cancerweight change and cancer

Weight differenceWeight differenceBMI differenceBMI difference% change (weight or BMI)% change (weight or BMI)–– [(measure at baseline minus measure at age [(measure at baseline minus measure at age

21) / measure at age 21]21) / measure at age 21]××100 100 % Average annual BMI change% Average annual BMI change–– % BMI change/(time between BMI measures)% BMI change/(time between BMI measures)

Multiethnic Cohort StudyMultiethnic Cohort StudyCohort established to study diet and chronic disease endpoints iCohort established to study diet and chronic disease endpoints in the US n the US among a multiethnic populationamong a multiethnic populationConsists of 215,251 adult men and women living in Hawaii and in Consists of 215,251 adult men and women living in Hawaii and in California.California.–– African Americans (16.3%) African Americans (16.3%) –– Latino (22.0%)Latino (22.0%)–– Japanese American (26.4%)Japanese American (26.4%)–– Native Hawaiian (6.5%) Native Hawaiian (6.5%) –– White (22.9%) White (22.9%) –– Other (5.8%).Other (5.8%).

Recruited in 1993Recruited in 1993--1996, Ages 451996, Ages 45--7575Males: 96,810 and Females: 118,441Males: 96,810 and Females: 118,441

Epidemiology of Endometrial CancerEpidemiology of Endometrial CancerThe fourth most common The fourth most common cancer among US cancer among US femalesfemales42,160 estimated new 42,160 estimated new cases for 2009.cases for 2009.Average 5 year survival Average 5 year survival rate is 83%.rate is 83%.White women have a White women have a higher incidence of higher incidence of endometrial cancer endometrial cancer compared to any other compared to any other ethnic group in the US.ethnic group in the US.However, AfricanHowever, African--American women have a American women have a mortality rate 79% greater mortality rate 79% greater than that of Caucasian than that of Caucasian women.women.

Risk factorsRisk factorsEstrogenEstrogen--only therapy in only therapy in postpost--menopausal womenmenopausal womenObesityObesityLate age at menopauseLate age at menopauseEarly age of menarcheEarly age of menarcheLimited epidemiological Limited epidemiological evidence for diabetes and evidence for diabetes and hypertension. hypertension.

Protective factorsProtective factorsUse of oral Use of oral contraceptivescontraceptivesIncreasing parityIncreasing paritySmokingSmoking

FollowFollow--up and Exclusion criteriaup and Exclusion criteriaFollowFollow--up:up:

FollowFollow--up time began at completion of baseline question, up time began at completion of baseline question, and continued until:and continued until:–– Diagnosis of endometrial cancerDiagnosis of endometrial cancer–– Death, or Death, or –– End of followEnd of follow--up (December 31, 2004)up (December 31, 2004)

Incident endometrial cancer cases were identified by Incident endometrial cancer cases were identified by record linkage to the Hawaii Tumor Registry, the Cancer record linkage to the Hawaii Tumor Registry, the Cancer Surveillance Program for Los Angeles County, and the Surveillance Program for Los Angeles County, and the California State cancer registry.California State cancer registry.

Exclusion criteria: Exclusion criteria: –– Had a hysterectomyHad a hysterectomy–– Previous history cancer other than Previous history cancer other than nonmelanomanonmelanoma skin cancerskin cancer–– missing variables of wmissing variables of weight at baseline or age 21, height, age at eight at baseline or age 21, height, age at

menarche, age at menopause, parity, oral contraceptive use, menarche, age at menopause, parity, oral contraceptive use, postmenopausal hormone therapy, smoking status, physical postmenopausal hormone therapy, smoking status, physical activity, and educationactivity, and education

Epidemiological data and Epidemiological data and Statistical AnalysisStatistical Analysis

Measures of height and weight were self reported Measures of height and weight were self reported on baseline questionnaireon baseline questionnaireCox proportional hazard models, age in days is Cox proportional hazard models, age in days is the underlying time variablethe underlying time variableIn preliminary analysis, we also adjusted for In preliminary analysis, we also adjusted for calories and physical activity and observed no calories and physical activity and observed no change in our findings. change in our findings. Final adjusted variables: education, body mass Final adjusted variables: education, body mass index, age at menarche, age at menopause, index, age at menarche, age at menopause, duration and type of hormone therapy, duration duration and type of hormone therapy, duration and oral contraceptive use, parity, smoking and oral contraceptive use, parity, smoking history, diabetes, hypertension and BMI at age 21.history, diabetes, hypertension and BMI at age 21.SAS v 9.1 (Cary, NC)SAS v 9.1 (Cary, NC)STATA v10 (College Station, TX)STATA v10 (College Station, TX)

Measures in adulthood more predictive of

endometrial cancer weight

Weight is a confounder

Similar findings as weight

Ethnic differences between BMI Ethnic differences between BMI and body fatand body fat

Hu FB, Obesity Epidemiology

Example: Physical activity and Example: Physical activity and endometrial cancerendometrial cancer

No. Cases RR1 (95% CI) RR2 (95% CI) RR3 (95% CI)

Physical activity (METs)3

Quartile 1: <1.4015 134 1.00 1.00 1.00Quartile 2: 1.4015 to

<1.5900123 0.86 (0.67,1.10) 0.86 (0.67, 1.10) 0.89 (0.70, 1.14)

Quartile 3: 1.5900 to <1.7576

116 0.78 (0.61, 1.01) 0.81 (0.63, 1.05) 0.86 (0.67, 1.11)

Quartile 4: ≥ 1.7576 119 0.81 (0.63, 1.04) 0.86 (0.67, 1.10) 0.92 (0.72, 1.19)P trend 0.072 0.198 0.493

1 Age-adjusted RR. 2 RRs were adjusted for age, ethnicity, education, age at menarche, menopausal status, age at menopause, duration and type of hormone therapy, oral contraceptive use, parity, smoking history, diabetes, and hypertension. 3 Additionally adjusted for BMI at baseline (quartiles).

BMI change and endometrial cancer

BMI at

Age 21 BMI at baseline

BMI change from age 21 to baseline

Endometrial Cancer

??

Confounding variables

r= 0.74

BMI change in Endometrial cancerBody weightchange (%)

No. Cases

RR1 (95% CI) RR2 (95% CI) RR3 (95% CI)

1.55 (0.87, 2.89)1.00

1.74 (1.12, 2.71)1.70 (1.08, 2.68)

RR4 (95% CI)

<-5 21 1.43 (0.82, 2.50) 1.37 (0.76, 2.46) 1.48 (0.83, 2.68)- 5 to <+5 30 1.00 1.00 1.005 to <15 87 1.66 (1.09, 2.51) 1.83 (1.17, 2.99) 1.79 (1.14, 2.79)15 to <25 86 1.67 (1.10, 2.54) 1.92 (1.23, 2.99) 1.81 (1.14, 2.86)25 to <35 72 1.80 (1.17, 2.77) 2.09 (1.32, 3.31) 1.63 (1.00, 2.65)

2.16 (1.34, 3.48)1.80 (1.09, 2.98)

≥ 35 196 3.10 (2.08, 4.62) 4.12 (2.69, 6.30) 2.60 (1.54, 4.39)

P trend <0.001 <0.001 0.044 0.0321RRs were adjusted for age, ethnicity, education, age at menarche, age at menopause, duration and type of hormone therapy, oral contraceptive use, parity, smoking history, diabetes, and hypertension.2 Model 1 and adjusting for BMI at age 21 (quartiles)3 Model 1 and adjusting for BMI at baseline (WHO categories)3 Model 1 and adjusting for BMI at age 21 (quartiles) and BMI at baseline (WHO categories)

Conclusions for BMI change and endometrial cancer

Limitations of study– Self reported weight

differential misclassification as a result of self-perceived weight– Cannot account for weight fluctuations– Selection bias from differing response rates by ethnic groups– No measures of WHR

Strengths of study– Prospective study design– Ability to control for a variety of confounding variables in a

multiethnic population.Conclusion– Adult BMI gain is associated with increased risk in endometrial

cancer– Risk may differ between ethnic groups, particular among

Japanese Americans– Postmenopausal hormone use and parity may modify the

endometrial cancer risk associated with adult BMI gain

The association between change in body The association between change in body mass index and upper mass index and upper aerodigestiveaerodigestive tract tract

cancers in the ARCAGE project: multicenter cancers in the ARCAGE project: multicenter casecase--control studycontrol study

Sungshim Lani Park1, 2, Yuan-Chin Amy Lee1, 2, Manuela Marron2, Antonio Agudo3, Wolfgang Ahrens4, Luigi Barzan5, Vladimir Bencko6, Simone Benhamou7, 8, Christine Bouchardy9, Cristina Canova10, Xavier Castellsague3, David I Conway11, 12, Claire M Healy13, Ivana Holcátová6, Kristina Kjaerheim14, Pagona Lagiou15, Raymond J Lowry16, Tatiana V Macfarlane17, Gary J Macfarlane17, Bernard E McCartan13, Patricia A McKinney11, 18, Franco Merletti19, Hermann Pohlabeln4, Lorenzo Richiardi19, Lorenzo Simonato10, Linda Sneddon16, Renato Talamini20, Dimitrios Trichopoulos21, Ariana Znaor22, Paul Brennan2, Mia Hashibe2

Manuscript in preparation/submissionManuscript in preparation/submission

Epidemiology of Upper Epidemiology of Upper AerodigestiveAerodigestive tract tract (UADT) Cancers(UADT) Cancers

Sites: Oral cavity, pharynx, Sites: Oral cavity, pharynx, hypopharynxhypopharynx larynx, larynx, esophagusesophagusNewly incident cases in the U.S.:Newly incident cases in the U.S.:–– Oral cavity and pharynx: 25,240 for males 10,480 for Oral cavity and pharynx: 25,240 for males 10,480 for

femalesfemales–– Larynx: 9,920 for males; 2370 for femalesLarynx: 9,920 for males; 2370 for females–– EsophagusEsophagus (both SCC and Adenocarcinoma)12,940 for (both SCC and Adenocarcinoma)12,940 for

males 3,530 for femalesmales 3,530 for femalesIn the U.S. 5 year survival is approximately 50%.In the U.S. 5 year survival is approximately 50%.EU estimated 180,000 new cases per year, causes EU estimated 180,000 new cases per year, causes 110,000 deaths (110,000 deaths (FerlayFerlay, 2004), 2004)Major risk factors include tobacco smoking and alcohol Major risk factors include tobacco smoking and alcohol drinking, however at least 25% of cases are attributed to drinking, however at least 25% of cases are attributed to other factors, such as low SES, poor nutrition, HPV, and other factors, such as low SES, poor nutrition, HPV, and leanness. leanness.

Rationale for leanness, UADT cancer association

Temporal ambiguityResidual confoundingBiological mechanism

leanness UADT cancer

http://www1.istockphoto.com/file_thumbview_approve/3686330/2/istockphoto_3686330-alcohol-drink.jpg

Prior Literature for UADT cancersPrior Literature for UADT cancersWeight measures from study entryAuthor Year Site Gender Measure OR (95% CI)Kabat 1994 Oral and pharyngeal Men Lowest quartile 3.09 (2.12, 4.5)

Women Lowest quartile 1.84 (0.92, 3.69)Franceschi 2001 Oral cavity and pharynx Men <22.7 kg/m2 3.78 (2.52, 5.67)

Women <22.7 kg/m2 1.99 (0.89, 4.44)Gaudet 2008 HNC Both < 18.5 kg/m2 2.11 (1.70, 2.61)Gallus 2003 Laryngeal Women >26 kg/m2 0.4 (0.2, 1.1)

Earlier Weight measuresAuthor Year Site Gender Time Measure OR (95% CI)Garavello 2006 Laryngeal Both Age 30 Lowest

quartile1.13 (0.71, 1.81)

Franceschi 2001 Oral cavity and pharynx

Men Age 30 <21.2 kg/m2 2.15 (1.34, 3.45)

Women Age 30 <21.2 kg/m2 1.21 (0.55, 2.64)Gaudet 2008 HNC Both Age 20 to 30 < 18.5 kg/m2 0.90 (0.68, 1.19)

Limitations of prior literatureLimitations of prior literature

Does not explain whether observed effect Does not explain whether observed effect is due to leanness as a result of weight is due to leanness as a result of weight change between these time points.change between these time points.Particularly since smoking and alcohol Particularly since smoking and alcohol drinking can affect body weight.drinking can affect body weight.

AlcoholAlcohol--related cancer and genetic related cancer and genetic susceptibility in Europe (ARCAGE) studysusceptibility in Europe (ARCAGE) study

Initialized by IARCInitialized by IARCStudy designed to investigate and clarify Study designed to investigate and clarify the role of smoking, drinking, and genetic the role of smoking, drinking, and genetic factors of UADT cancers.factors of UADT cancers.14 14 centerscenters and 10 European countriesand 10 European countriesRecruitment between 2002Recruitment between 2002--20052005

Cases and ControlsCases and Controls2,304 newly diagnosed cases (2,109 eligible 2,304 newly diagnosed cases (2,109 eligible squamoussquamouscell carcinoma (SCC) and 195 eligible noncell carcinoma (SCC) and 195 eligible non--SCC cases)SCC cases)Case eligibility: UADT cancer according to ICDCase eligibility: UADT cancer according to ICD--O3.O3.All ARCAGE centers used hospitalAll ARCAGE centers used hospital--based controls, based controls, except for UK center.except for UK center.2,227 controls, frequency matched to cases by sex, age 2,227 controls, frequency matched to cases by sex, age (5(5--year interval), and referral (or residence) area.year interval), and referral (or residence) area.Control eligibility include recent disease diagnosis, not Control eligibility include recent disease diagnosis, not related to alcohol, tobacco, or dietary practices, and related to alcohol, tobacco, or dietary practices, and short hospital stay.short hospital stay.

Epidemiological dataEpidemiological dataEpidemiological data collection was performed by Epidemiological data collection was performed by identical interviewers using a lifestyle questionnaireidentical interviewers using a lifestyle questionnaire3 measures of weight: time of recruitment, 2 years 3 measures of weight: time of recruitment, 2 years prior to recruitment, 30 years of age.prior to recruitment, 30 years of age.–– Weight at study entry (interviewer measured)Weight at study entry (interviewer measured)

Not available at UK sitesNot available at UK sites

–– Weights at 2 years prior and age 30 (self reported)Weights at 2 years prior and age 30 (self reported)Not available for Paris siteNot available for Paris site

% BMI change = % BMI change = (BMI at 2 years prior to study entry (BMI at 2 years prior to study entry --BMI at age BMI at age 30)/BMI at age 30 30)/BMI at age 30

Statistical AnalysesStatistical AnalysesExcluded: Excluded: –– 195 non195 non--SCC cases, due to limitation in sample sizeSCC cases, due to limitation in sample size–– 63 SCC cases and 54 controls for missing data.63 SCC cases and 54 controls for missing data.

Adjustment variables: Adjustment variables: centercenter, education, sex, age, fruit , education, sex, age, fruit and vegetable intake, tobacco status/frequency, and and vegetable intake, tobacco status/frequency, and alcohol frequency.alcohol frequency.Performed using SAS v9.1 (Cary, NC)Performed using SAS v9.1 (Cary, NC)Unconditional logistic regression model.Unconditional logistic regression model.

Baseline characteristics for ARCAGESCC UADT Mean distribution of BMI 2 years ago Mean % BMI change (age 30 to 2 years prior)Ca Co Ca Co Ca Co

Total (N) 2048 2173 25.1 26.3 4.2 9.0Center % % mean (SD) mean (SD) mean (SD) mean (SD)

Prague 7.8 7.8 26.4 (4.4) 26.9 (4.1) 10.6 (16.2) 12.0 (15.6)Bremen 13.3 15.0 25.7 (5.2) 27.3 (5.2) 4.1 (19.3) 11.3 (17.3)Athens 10.1 8.9 26.7 (4.3) 26.9 (4.5) 9.1 (17.5) 14.0 (18.2)Aviano 7.0 7.0 26.3 (4.0) 27.2 (3.7) 10.1 (15.6) 12.3 (15.3)Padova 6.3 6.0 25.0 (4.2) 27.0 (4.1) 8.4 (15.4) 13.5 (15.4)Turin 7.6 9.0 25.0 (5.0) 26.2 (3.9) 10.7 (18.3) 11.2 (14.5)Dublin 1.5 0.8 25.8 (7.2) 25.6 (5.9) 3.9 (17.8) 6.7 (10.7)Oslo 6.6 8.2 24.7 (3.9) 25.9 (5.0) 7.0 (17.3) 11.8 (19.0)Glasgow 4.2 4.1 24.6 (4.6) 26.5 (4.9) 6.3 (13.8) 13.5 (17.6)Manchester 6.7 8.5 26.0 (4.4) 26.7 (4.3) 5.6 (16.1) 9.9 (14.4)Newcastle 3.2 5.2 25.7 (4.9) 26.9 (5.1) 7.8 (13.9) 10.0 (14.4)Barcelona 8.8 7.5 24.9 (4.6) 26.6 (4.7) 5.5 (16.5) 7.5 (21.2)Zagreb 2.4 2.1 25.7 (4.0) 26.1 (4.0) 4.0 (17.0) 2.5 (14.2)Paris* 14.6 10.0 NA NA NA NA

P-value** <0.001 0.069 <0.001 0.002Age

<40 years 2.3 4.8 23.6 (4.5) 25.1 (5.8) 0.9 (12.3) 1.2 (9.7)40-44 years 4.6 5.3 25.4 (4.9) 26.2 (4.8) 4.1 (13.7) 9.6 (14.1)45-49 years 10.2 8.6 24.8 (4.8) 26.9 (5.6) 3.3 (10.8) 8.7 (15.2)50-54 years 15.0 14.4 24.8 (4.1) 27.1 (5.3) 5.9 (15.0) 11.5 (14.9)55-59 years 21.0 17.6 25.8 (4.5) 27.3 (4.5) 7.3 (15.5) 13.4 (18.8)60-64 years 16.9 14.0 26.0 (4.2) 27.2 (4.3) 8.4 (17.6) 12.8 (16.0)65-69 years 14.6 15.3 26.2 (5.5) 26.7 (3.9) 9.5 (20.7) 11.4 (15.9)70-74 years 9.1 11.2 25.9 (4.2) 26.8 (3.8) 10.2 (18.6) 11.9 (19.7)75+ years 6.5 8.8 26.0 (4.8) 25.6 (3.6) 7.7 (21.1) 8.7 (17.2)

P-value** <0.001 <0.001 <0.001 <0.001 <0.001

SCC UADTMean distribution of BMI 2 years

agoMean % BMI change (age 30 to 2

years prior)Ca Co Ca Co Ca Co

Sex % % Mean (SD) Mean (SD) Mean (SD) Mean (SD)Men 81.5 75.3 25.7 (4.4) 26.8 (4.3) 6.4 (16.1) 9.9 (15.0)Women 18.5 24.7 25.2 (5.5) 26.5 (5.2) 11.1 (19.9) 15.0 (20.6)

P-value** <0.001 0.059 0.164 <0.001 <0.001Histology

Oral/Oropharynx 47.4 25.5 (4.8) 6.9 (17.8)Hypopharynx/Larynx 40.4 25.8 (4.4) 7.2 (15.8)Esophageal 7.2 25.5 (4.7) 9.5 (17.3)Overlapping 5.0 25.6 (4.3) 8.5 (18.0)

P-value** 0.778 0.389Education

Finished primary school 37.1 26.4 25.8 (4.4) 27.2 (4.4) 8.9 (17.4) 12.5 (19.6)Finished further school 56.9 62.8 25.5 (4.8) 26.8 (4.7) 6.4 (17.0) 11.2 (16.1)University degree 6.0 10.9 25.4 (4.3) 25.1 (3.7) 6.7 (13.6) 7.8 (12.9)

P-value** <0.001 0.292 <0.001 0.024 0.007Fruit and Vegetable intake

Low 59.0 38.7 25.2 (4.6) 26.9 (4.9) 6.5 (16.9) 11.5 (17.1)Mid 25.8 35.9 26.1 (4.6) 26.5 (4.3) 8.7 (16.9) 10.1 (15.7)High 15.2 25.4 26.4 (4.7) 26.9 (4.6) 8.3 (17.6) 12.5 (18.0)P-value** <0.001 <0.001 0.308 0.049 0.067

Baseline characteristics for ARCAGE, con’t.

SCC UADT Mean distribution of BMI 2 years agoMean % BMI change (age 30 to 2

years prior)Ca Co Ca Co Ca Co

Tobacco smoking status and frequency

Never smoker 8.7 32.8 26.9 (4.9) 26.8 (4.6) 11.9 (18.6) 11.4 (16.6)Former smoker

(0<packyear≤20) 7.6 18.3 27.0 (4.6) 26.7 (4.1) 11.4 (16.1) 11.9 (16.5)Former smoker (20< packyears≤40) 8.3 10.0 27.0 (4.2) 27.5 (4.2) 11.1 (18.3) 13.4 (16.8)Former smoker

(40≥packyears) 7.7 5.8 26.9 (4.8) 27.8 (4.4) 11.4 (14.5) 16.0 (21.0)Current smoker

(0<packyears≤20) 8.5 10.1 24.8 (4.4) 25.8 (4.2) 7.9 (15.2) 8.1 (13.9)Current smoker (20< packyears≤40) 25.7 11.9 24.6 (4.8) 26.7 (4.8) 4.6 (17.5) 10.2 (16.4)Current smoker

(packyears≥40) 33.6 11.2 25.3 (4.2) 26.3 (6.0) 5.0 (16.3) 7.6 (17.8)P-value** <0.001 <0.001 <0.001 <0.001 <0.001

Alcohol FrequencyNever 5.7 12.5 26.7 (5.9) 27.1 (4.9) 12.0 (20.8) 11.5 (22.4)<1drink per day 23.9 38.8 25.6 (4.5) 26.6 (4.7) 7.7 (17.9) 11.9 (15.5)1 to 2 drinks/day 27.2 31.4 25.9 (5.0) 26.7 (3.8) 8.9 (17.7) 10.8 (15.6)3 to 4 drinks/day 18.9 10.6 25.9 (4.3) 26.9 (5.7) 7.0 (15.6) 10.3 (17.7)5+ drinks/day 24.3 6.72 25.0 (4.1) 27.2 (4.6) 4.5 (14.9) 9.2 (16.2)

P-value** <0.001 0.003 0.287 <0.001 0.430

Baseline characteristics for ARCAGE, con’t.

Table 3. Association between BMI, height, and BMI change and UADT SCCsCa Co OR* 95% CI

BMI at study entry (kg/m2)**13.0 to 18.4 139 46 1.90 (1.28, 2.82)18.5 to 24.9 915 670 1.0025.0 to 29.9 486 768 0.54 (0.46, 0.65)30.0 to 53.0 176 277 0.55 (0.43, 0.71)Missing 13 9Ptrend <0.001

BMI at 2 years prior to interview (kg/m2) †

13.0 to 18.4 57 23 2.10 (1.16, 3.81)18.5 to 24.9 785 688 1.0025.0 to 29.9 613 863 0.74 (0.62, 0.88)30.0 to 53.0 252 361 0.74 (0.59, 0.93)Missing 42 21Ptrend <0.001

BMI at age 30 (kg/m2) †

13.0 to 18.4 61 57 1.10 (0.72, 1.69)18.5 to 24.9 1066 1188 1.0025.0 to 29.9 401 467 1.02 (0.84, 1.22)30.0 to 53.0 116 146 0.94 (0.70, 1.27)Missing 105 98Ptrend 0.721

Percent BMI change from age 30 to 2 years prior interview†

<−5% (BMI loss) 280 202 1.15 (0.89, 1.49)−5% to < +5% (stable) 566 501 1.00≥ +5% (BMI gain) 788 1154 0.75 (0.62, 0.89)Missing 115 99Ptrend <0.001

*Adjusted for center, education, sex, age, fruit and vegetable intake, tobacco status/frequency, and alcohol frequency.** UK and Dublin centers not included in the model† Paris not included in the model.

Associations between BMI, BMI change and UADT cancers, stratified by subsite

Oral-oropharyngeal Hypopharynx and larynx EsophagealCa Co OR* 95% CI Ca Co OR* 95% CI Ca Co OR* 95% CI

BMI at study entry (kg/m2)**

13.0 to 18.4 75 46 2.11 (1.36, 3.28) 46 46 1.55 (0.91, 2.63) 12 46 5.43 (2.16, 13.64)18.5 to 24.9 430 670 1.00 390 670 1.00 65 645 1.0025.0 to 29.9 208 768 0.48 (0.39, 0.60) 225 768 0.60 (0.47, 0.76) 37 751 0.45 (0.28, 0.73)30.0 to 53.0 75 277 0.46 (0.33, 0.63) 82 277 0.62 (0.45, 0.86) 12 273 0.30 (0.15, 0.61)Ptrend <0.001 <0.001 <0.001

BMI at 2 years prior to interview (kg/m2) †

13.0 to 18.4 31 23 2.04 (1.04, 3.99) 12 23 1.35 (0.52, 3.51) 10 21 4.95 (1.70, 14.46)18.5 to 24.9 395 688 1.00 305 688 1.00 59 596 1.0025.0 to 29.9 302 863 0.76 (0.62, 0.94) 240 863 0.66 (0.52, 0.83) 49 768 0.70 (0.45, 1.10)30.0 to 53.0 122 361 0.71 (0.54, 0.94) 93 361 0.62 (0.45, 0.84) 26 323 0.75 (0.43, 1.29)Ptrend <0.001 <0.001 0.018

BMI at age 30 (kg/m2) †

13.0 to 18.4 36 57 1.18 (0.72, 1.94) 19 57 1.19 (0.63, 2.25) 4 54 0.66 (0.21, 2.04)18.5 to 24.9 524 1188 1.00 398 1188 1.00 103 1048 1.0025.0 to 29.9 201 467 1.09 (0.87, 1.37) 152 467 0.94 (0.73, 1.21) 33 412 0.79 (0.49, 1.26)30.0 to 53.0 62 146 0.96 (0.67, 1.37) 43 146 0.98 (0.65, 1.48) 3 122 0.23 (0.07, 0.77)Ptrend 0.969 0.612 0.037

Percent BMI change from age 30 to 2 years prior to interview †

<−5% (BMI loss) 151 202 1.22 (0.90, 1.64) 92 202 0.87 (0.61, 1.24) 24 177 1.52 (0.81, 2.86)−5% to < +5%

(stable) 286 501 1.00 223 501 1.00 40 428 1.00≥ +5% (BMI gain) 380 1154 0.71 (0.57, 0.88) 300 1154 0.66 (0.51, 0.84) 79 1030 0.84 (0.53, 1.33)Ptrend 0.002 0.007 0.051

*Adjusted for center, education, sex, age, fruit and vegetable intake, tobacco status/frequency, and alcohol frequency.

Variable BMI change from age 30 to 2 years prior to study entryLoss (<-5%) (−5% to < +5%) Gain (≥ +5%) Ptrend

Smoking StatusNever smoking

cases/controls 23/71 36/171 102/430OR (95% CI)* 1.23 (0.65, 2.33) 1.00 0.95 (0.60, 1.50) 0.398

Former smokingcases/controls 52/67 93/161 247/431OR (95% CI)* 1.19 (0.73, 1.94) 1.00 0.93 (0.67, 1.29) 0.284

Current smokingcases/controls 205/64 437/169 439/293OR (95% CI)* 1.08 (0.75, 1.54) 1.00 0.59 (0.46, 0.76) <0.001

Drinking StatusNever drinking


Former drinkingcases/controls 55/32 89/39 110/106OR (95% CI)* 0.83 (0.42, 1.65) 1.00 0.44 (0.25, 0.78) 0.015

Current drinkingcases/controls 211/129 453/408 624/914OR (95% CI)* 1.28 (0.95, 1.74) 1.00 0.79 (0.64, 0.96) <0.001

Associations between BMI change and UADT cancers, stratified by risk factors


Associations between BMI change and UADT cancers, stratified by risk factors, con’t.Loss (<-5%) (−5% to < +5%) Gain (≥ +5%) Ptrend

Smoking and Drinking statusNever smokes and drinks


No drinking but smokescases/controls 8/18 15/18 31/44OR (95% CI)* 0.30 (0.07, 1.21) 1.00 0.73 (0.25, 2.13) 0.277

No smoking but drinkscases/controls 17/48 27/135 79/340OR (95% CI)* 1.28 (0.60, 2.76) 1.00 0.95 (0.56, 1.62) 0.429

Smokes and drinkscases/controls 249/113 515/312 655/680OR (95% CI)* 1.19 (0.89, 1.59) 1.00 0.63 (0.52, 0.77) <0.001

Fruit and Vegetable intakeLow fruits and vegetables

cases/controls 171/70 369/203 442/477OR (95% CI)* 1.26 (0.86, 1.83) 0.63 (0.49, 0.81) <0.001

Medium fruit and vegetablescases/controls 67/90 138/178 240/426OR (95% CI)* 0.76 (0.48, 1.20) 0.85 (0.56, 1.62) 0.956

High fruit and vegetablescases/controls 42/42 59/120 655/680OR (95% CI)* 2.06 (1.10, 3.86) 1.03 (0.64, 1.64) 0.047


Loss (<-5%) (−5% to < +5%) Gain (≥ +5%) PtrendBMI at age 30<18.5kg/m2

cases/controls 2/0 16/7 41/50OR (95% CI)* -- 1.00 0.18 (0.02, 1.46) 0.081

18.5kg/m2 to <25 kg/m2

cases/controls 120/62 401/314 538/810OR (95% CI)* 1.50 (1.00, 2.24) 1.00 0.72 (0.57, 0.90) <0.001

25kg/m2 to <30 kg/m2


≥30kg/m2


Time between age 30 and interviewQuartile 1


Quartile 2cases/controls 89/42 176/139 237/327OR (95% CI)* 1.68 (1.00, 2.81) 1.00 0.78 (0.56, 1.09) 0.002



Associations between BMI change and UADT cancers, stratified by risk factors, con’t.

Limitations, Strengths and ConclusionsLimitations– Self-reported measures of weight– No WHR– Use of semi-food frequency questionnaire limited the

possibility to account for energy balanceStrengths– large sample size– BMI measures at different time points– the potential to adjust for a variety of smoking and

drinking measures. Conclusions– BMI gain is inversely associated with UADT cancers – This may be due to alterations in smoking and/or

drinking behaviors– BMI change may also serve as a potential indicator of

early tumor development among a smoking and alcohol drinking population.

The association between change The association between change in body mass index and lung and in body mass index and lung and upper aeroupper aero--digestive tract cancersdigestive tract cancers

Sungshim Lani Park1, Yuan-Chin Amy Lee1, Yan Cui1, Mia Hashibe2, Sander Greenland1,3, Hal Morgenstern5, Donald P. Tashkin6, Jenny T. Mao6, Wendy Cozen6, Thomas M. Mack6, Zuo-Feng Zhang1, 4

Manuscript in preparationManuscript in preparation

Epidemiology of Lung CancerEpidemiology of Lung CancerHighest incidence secondary to prostate and breast Highest incidence secondary to prostate and breast cancercancer–– 116,090 estimated new male cases for 2009116,090 estimated new male cases for 2009–– 103,350 estimated new female cases for 2009103,350 estimated new female cases for 2009

The highest mortality rate The highest mortality rate –– Estimated deaths for males: 88,900 Estimated deaths for males: 88,900 –– Estimated deaths for females: 70,490 Estimated deaths for females: 70,490

Poorest survivalPoorest survival–– FiveFive--year survival rate of 15% from 1996year survival rate of 15% from 1996--2004.2004.11

1 Jemal A, et al., ACS Annual report, Cancer Statistics 2009.

Risk factors for lung and UADT cancersRisk factors for lung and UADT cancersLungLung cancerscancers

Tobacco smokingTobacco smokingGenderGenderPassive smokePassive smokeRadon gasRadon gasIndoor air pollutionIndoor air pollutionPoor dietPoor diet(Alcohol drinking) (Alcohol drinking) (HPV)(HPV)

UADT cancersUADT cancersTobacco smokingTobacco smokingAlcohol drinkingAlcohol drinkingGender Gender Low SESLow SESHPVHPVPoor dietPoor dietPoor dentition Poor dentition

Prior studies investigating weight Prior studies investigating weight change and lung cancerschange and lung cancers

Author year journalstudy design study

weight measure

difference RR LL UL

Kabat 2007 epidemiology cohort

Canadian National Breast Screening Study

1 year prior

18 years women 50 lbs+ 0.5 0.22 1.12

Kabat 2008 AJE cohort WHI baseline 18 years

women never smokers 30 lbs+ 0.76 0.45 1.3


women former smokers 30 lbs+ 0.76 0.56 1.03


women current 30 lbs+ 0.63 0.43 0.93

Los Angeles Lung and UADT cancer studyLos Angeles Lung and UADT cancer studyPopulation Based CasePopulation Based Case--Control StudyControl Study–– 611 Cases and 1040 controls611 Cases and 1040 controls–– Newly diagnosed cases obtained using the rapid ascertainment Newly diagnosed cases obtained using the rapid ascertainment

system of the Cancer Surveillance Program for L.A. County, system of the Cancer Surveillance Program for L.A. County, administered by the Keck School of Medicine and Norris administered by the Keck School of Medicine and Norris Comprehensive Cancer Center (USC).Comprehensive Cancer Center (USC).

–– Controls were identified using a formal algorithm providing a liControls were identified using a formal algorithm providing a list st of households within the neighborhood of each individual case. of households within the neighborhood of each individual case.

–– Controls were matched to cases by age and gender.Controls were matched to cases by age and gender.Study CriteriaStudy Criteria–– Subjects were residents of LA County at time of recruitment Subjects were residents of LA County at time of recruitment

(1999(1999--2004).2004).–– During the study period were 18During the study period were 18--65 years of age.65 years of age.–– Subjects were able to speak either English or Spanish.Subjects were able to speak either English or Spanish.

Epidemiological data and statistical analysisEpidemiological data and statistical analysisEpidemiological dataEpidemiological data

Epidemiological data collection was performed by Epidemiological data collection was performed by identical interviewers using a lifestyle questionnaireidentical interviewers using a lifestyle questionnaire2 measures of weight: 1 year prior to recruitment 2 measures of weight: 1 year prior to recruitment and weight at age 21. and weight at age 21. % BMI change = (BMI at 2 years prior to study entry % BMI change = (BMI at 2 years prior to study entry -- BMI at age 30)/ BMI at age 30BMI at age 30)/ BMI at age 30

Statistical analysisStatistical analysisAnalyzed using unconditional logistic regression.Analyzed using unconditional logistic regression.Matching was broken allowing us to include cases Matching was broken allowing us to include cases without match controls.without match controls.SAS v9.1SAS v9.1Adjustment variables: gender, smoking status, packAdjustment variables: gender, smoking status, pack--years, education, race, calories, and age (and years, education, race, calories, and age (and drinking for UADT cancers)drinking for UADT cancers)

Table I. Baseline characteristicsTable I. Baseline characteristicsVariableVariable Lung cancerLung cancer SCC UADT cancerSCC UADT cancer ControlsControls

N=611N=611 N=527N=527 N=1040N=1040

EthnicityEthnicityWhiteWhite 359 359 (58.8)(58.8) 289289 (54.8)(54.8) 634 634 (61.0)(61.0)

HispanicHispanic 53 53 (8.7)(8.7) 6262 (11.8)(11.8) 150 150 (14.4)(14.4)

BlackBlack 96 96 (15.7)(15.7) 68 68 (12.9)(12.9) 102 102 (9.8)(9.8)

AsianAsian 70 70 (11.5)(11.5) 59 59 (11.2)(11.2) 62 62 (6.0)(6.0)

otherother 32 32 (5.2)(5.2) 47 47 (8.9)(8.9) 9191 (8.8)(8.8)MissingMissing 1 1 (0.16)(0.16) 2 2 (0.4)(0.4) 11 (0.1)(0.1)

SexSexMaleMale 303 303 (49.6)(49.6) 454 454 (75.5)(75.5) 623 623 (59.9)(59.9)

FemaleFemale 308 308 (50.4)(50.4) 147 147 (24.5)(24.5) 417 417 (40.1)(40.1)

Age, meanAge, mean 52.2 52.2 ±± 5.45.4 50.3 50.3 ±± 7.67.6 49.9 49.9 ±± 7.37.3missingmissing 00 00 00

BMI, meanBMI, mean 26.3 26.3 ±± 5.75.7 26.7 26.7 ±± 5.85.8 27.5 27.5 ±± 5.75.7

missingmissing 22 22 22

BMI at age 21, meanBMI at age 21, mean 22.1 22.1 ±± 3.43.4 22.9 22.9 ±± 3.73.7 22.6 22.6 ±± 3.73.7

missingmissing 1313 1414 88

Table 1, continuedTable 1, continuedVariableVariable Lung cancerLung cancer SCC UADT cancerSCC UADT cancer ControlsControls

N=611N=611 N=527N=527 N=1040N=1040Education Level

0-12 265 (43.4) 240 (45.5) 300 (28.9)12-16 275 (45.0) 230 (43.6) 481 (46.3)<16 71 (11.6) 57 (10.8) 258 (24.8)missing 0 0 0 0 1 (0.10)

Smoking StatusNever 110 (18.0) 164 (31.1) 492 (47.3)Former 360 (58.9) 272 (51.6) 362 (34.8)Current 141 (23.1) 91 (17.3) 186 (17.9)

Drinking StatusNever 170 (27.8) 104 (19.7) 264 (25.4)Former 250 (40.9) 272 (51.6) 199 (26.1)Current 190 (31.1) 149 (28.3) 199 (19.1)missing 1 (0.16) 2 (0.4) 4 (0.4)

CaloriesCalories 1529 ± 667.1 1750.5 ± 864.5 1483.8 ± 602.0Fruit and Vegetable intake

Quartile 1 209 (34.2) 170 (32.3) 260 (25.0)Quartile 2 145 (23.7) 119 (22.6) 259 (24.9)Quartile 3 133 (21.8) 114 (21.6) 257 (24.7)Quartile 4 115 (18.8) 117 (22.2) 258 (24.8)missing 9 (1.5) 7 (1.3) 6 (0.6)

Table 2. Association between anthropometric measures and lung cancerVariables Cases/Controls Crude OR (95% CI) Adjust OR1 (95% CI)BMI at age 21

<20.34 187/255 1.00 1.0020.34 to <22.15 148/259 0.78 (0.59, 1.03) 0.96 (0.69, 1.35)22.15 to <24.34 129/262 0.67 (0.51, 0.89) 0.86 (0.60, 1.22)≥24.34 134/248 0.74 (0.56, 0.98) 0.90 (0.62, 1.30)P Trend 0.016 0.467

BMI at baseline<18.5 kg/m2 18/13 1.89 (0.91, 3.94) 1.27 (0.52, 3.01)18.5 to <25 263/360 1.00 1.0025 to <30 214/397 0.74 (0.59, 0.93) 0.83 (0.62, 1.11)>30 114/257 0.61 (0.46, 0.80) 0.55 (0.39, 0.77)P Trend <0.001 <0.001

BMI change<−5% (weight loss) 51/39 1.61 (0.99, 2.61) 0.99 (0.55, 1.80)−5% to <+5% 113/139 1.00 1.005% to <15% 132/256 0.63 (0.46, 0.88) 0.75 (0.50, 1.13)15% to <25% 113/214 0.65 (0.46, 0.91) 0.70 (0.46, 1.06)25% to <35% 67/153 0.54 (0.37, 0.79) 0.50 (0.31, 0.80)>35% 122/222 0.68 (0.48, 0.94) 0.50 (0.32, 0.76)P trend <0.001 <0.001

Average annual weight change<0% 72/58 1.73 (1.14 , 2.63) 1.08 (0.64, 1.82)0 to <0.25% 119/166 1.00 1.000.25 to <0.5% 108/173 0.87 (0.62, 1.22) 0.81 (0.53, 1.22)0.5 to <0.75% 80/159 0.70 (0.49, 1.00) 0.72 (0.46, 1.11)0.75 to <1% 67/135 0.69 (0.48, 1.01) 0.67 (0.42, 1.07)≥ 1% 152/332 0.64 (0.47, 0.87) 0.50 (0.34, 0.74)P trend <0.001 <0.001

Adjustment variables: gender, smoking status, packAdjustment variables: gender, smoking status, pack--years, education, race, calories, and ageyears, education, race, calories, and age

Male FemalesVariables Ca/Co ORc (95% CI) Adj OR1 (95% CI) Ca/Co ORc (95% CI) Adj OR1 (95% CI)BMI at age 21

<20.34 48/96 1.00 1.00 139/159 1.00 1.0020.34 to <22.15 58/144 0.81 (0.51, 1.28) 1.05 (0.59, 1.87) 90/115 0.90 (0.63, 1.28) 1.01 (0.66, 1.54)22.15 to <24.34 89/179 0.99 (0.65, 1.53) 1.25 (0.73, 2.15) 40/83 0.55 (0.35, 0.86) 0.57 (0.33, 0.96)≥24.34 101/195 1.04 (0.68, 1.58) 1.31 (0.76, 2.25) 33/53 0.71 (0.44, 1.16) 0.54 (0.30, 0.98)P Trend 0.502 0.240 0.021 0.011

BMI at baseline<18.5 kg/m2 5/4 1.86 (0.49, 7.08) 1.95 (0.37, 10.2) 13/9 1.84 (0.76, 4.42) 1.10 (0.40, 3.05)18.5 to <25 116/173 1.00 1.00 147/187 1.00 1.0025 to <30 122/292 0.62 (0.45, 0.85) 0.75 (0.51, 1.12) 92/105 1.11 (0.78, 1.59) 0.88 (0.57, 1.34)>30 59/147 0.60 (0.41, 0.88) 0.62 (0.38, 1.01) 55/110 0.64 (0.43, 0.94) 0.43 (0.26, 0.70)P Trend 0.002 0.029 0.018 0.001

BMI change<−5% 30/24 1.70 (0.91, 3.16) 1.34 (0.60, 2.97) 21/15 1.46 (0.67, 3.17) 0.84 (0.34 , 2.09)−5% to <+5% 67/91 1.00 1.00 46/48 1.00 1.00>5% 199/499 0.54 (0.38, 0.77) 0.62 (0.39, 0.98) 235/346 0.71 (0.46, 1.10) 0.63 (0.37, 1.08)P trend <0.001 0.012 0.013 0.138

Average annual weight change<0% 43/31 2.53 (1.46, 4.38) 1.94 (0.95, 3.96) 29/27 0.88 (0.46, 1.72) 0.64 (0.29, 1.42)0 to <0.25% 68/124 1.00 1.00 51/42 1.00 1.000.25 to <0.5% 61/114 0.98 (0.64, 1.50) 0.97 (0.56, 1.66) 47/59 0.66 (0.37, 1.15) 0.63 (0.33, 1.23)0.5 to <0.75% 39/109 0.65 (0.41, 1.04) 0.75 (0.42, 1.34) 41/50 0.68 (0.38, 1.21) 0.61 (0.30, 1.21)0.75 to <1% 35/84 0.76 (0.46, 1.24) 0.87 (0.47, 1.62) 32/51 0.52 (0.28, 0.94) 0.46 (0.22, 0.95)≥ 1% 50/152 0.60 (0.39, 0.93) 0.63 (0.36, 1.10) 102/180 0.47 (0.29, 0.75) 0.37 (0.21, 0.66)P trend <0.001 0.007 <0.001 0.001

Table 2. Association between anthropometric measures and lung cancer, stratified by gender

Adjustment variables: smoking status, packAdjustment variables: smoking status, pack--years, education, race, calories, and ageyears, education, race, calories, and age

NSCLC SCLCVariables Ca/Co Adjust OR1 (95% CI) Ca/Co Adjust OR1 (95% CI)BMI at age 21

<20.34 162/255 1.00 19/255 1.0020.34, <22.15 121/259 0.88 (0.62, 1.26) 18/259 1.21 (0.54, 2.67)22.15, <24.34 110/262 0.80 (0.55, 1.16) 13/262 0.78 (0.32, 1.86)≥24.34 106/248 0.77 (0.52, 1.13) 22/248 2.13 (0.96, 4.72)

P Trend 0.151 0.127BMI at baseline kg/m2

<18.5kg/m2 17/13 1.37 (0.57, 3.30) 0/13 -18.5 to <25 221/360 1.00 33/360 1.0025 to <30 174/397 0.78 (0.58, 1.06) 24/397 0.58 (0.30, 1.13)>30 94/257 0.53 (0.37, 0.76) 17/257 0.55 (0.27, 1.14)

P Trend <0.001 0.126BMI change

<−5% (weight loss)

46/39 1.18 (0.64, 2.16) 4/39 0.27 (0.07, 1.09)

−5% to <+5% 93/138 1.00 17/139 1.005% to <25% 201/470 0.71 (0.48, 1.04) 29/470 0.47 (0.22, 1.00)>25% 159/375 0.53 (0.35, 0.79) 22/375 0.21 (0.09, 0.49)

P Trend <0.001 0.013Average annual weight change

<0% 65/58 1.27 (0.74, 2.16) 6/58 0.40 (0.12, 1.31)0 to <0.25% 96/166 1.00 19/166 1.000.25 to <0.5% 89/173 0.83 (0.53, 1.28) 15/173 0.67 (0.29, 1.52)0.5 to <0.75% 62/159 0.67 (0.42, 1.06) 9/159 0.46 (0.18, 1.20)0.75 to <1% 59/135 0.76 (0.47, 1.23) 5/135 0.22 (0.06, 0.72)≥ 1% 128/332 0.55 (0.36, 0.82) 18/332 0.26 (0.11, 0.61)

P Trend <0.001 0.004

Table 2. Association between anthropometric measures and lung cancer, stratified by subsite

Adjustment variables: smoking status packAdjustment variables: smoking status pack years education race calories and ageyears education race calories and age

Association between BMI change and lung cancer, stratified by riAssociation between BMI change and lung cancer, stratified by risk factorssk factors

<−5% (weight loss) −5% to +5% 5% to <25% ≥25% PtrendBMI at age 21Tertile 1

case/controls 5/1 39/36 90/137 102/169OR (95% CI)* 2.22 (0.22, 22.89) 1.00 0.64 (0.33, 1.23) 0.42 (0.21, 0.81) 0.002

Tertile 2case/controls 21/8 32/51 81/174 53/113OR (95% CI)* 2.50 (0.85, 7.38) 1.00 0.87 (0.46, 1.64) 0.62 (0.31, 1.23) 0.010

Tertile 3case/controls 25/30 42/52 74/159 34/93OR (95% CI)* 0.60 (0.25, 1.45) 1.00 0.64 (0.33, 1.23) 0.47 (0.22, 1.00) 0.225

Never smokingcase/controls 4/12 10/70 54/224 37/176OR (95% CI)* 1.24 (0.28, 5.56) 1.00 1.32 (0.60, 2.90) 0.95 (0.41, 2.17) 0.531

Former smokingcase/controls 30/15 63/42 142/168 120/132OR (95% CI)* 1.18 (0.48, 2.91) 1.00 0.82 (0.47, 1.42) 0.55 (0.31, 0.99) 0.012

Current smokingcase/controls 17/12 40/27 49/78 32/67OR (95% CI)* 0.62 (0.22, 1.74) 1.00 0.36 (0.17, 0.73) 0.23 (0.10, 0.50) <0.001


Association between BMI change and lung cancer, stratified by riAssociation between BMI change and lung cancer, stratified by risk factors, sk factors, concon’’tt..<−5% (weight loss) −5% to +5% 5% to <25% ≥25% Ptrend

Fruit and Vegetable intakeQuartile 1

case/controls 14/10 49/38 77/109 66/95OR (95% CI)* 0.43 (0.14, 1.33) 1.00 0.68 (0.35, 1.32) 0.33 (0.16, 0.67) 0.018

Quartile 2case/controls 14/5 23/36 58/121 45/93OR (95% CI)* 2.87 (0.68, 12.17) 1.00 0.76 (0.34, 1.69) 0.54 (0.23, 1.28) 0.011



Time to diseasecase/controls 6/13 17/48 36/110 22/66OR (95% CI)* 0.27 (0.06, 1.36) 1.00 0.73 (0.32, 1.63) 0.56 (0.22, 1.42) 0.842

Quartile 2case/controls 8/9 25/29 66/123 41/98OR (95% CI)* 0.52 (0.13, 2.08 ) 1.00 0.55 (0.25, 1.21) 0.33 (0.14, 0.75) 0.024




Association between BMI, BMI change and UADT cancersAssociation between BMI, BMI change and UADT cancersVariables Ca/Co Crude OR (95% CI) Adjust OR1(95% CI)BMI at age 21

<20.34 111/255 1.00 1.0020.34 to <22.15 108/260 0.95 (0.70, 1.31) 0.94 (0.66, 1.35)22.15 to <24.34 153/264 1.33 (0.99, 1.80) 1.10 (0.77, 1.56)

≥24.34 141/253 1.28 (0.95, 1.73) 1.26 (0.88, 1.81)P Trend 0.027 0.127

BMI at baseline<18.5 kg/m2 13/13 1.78 (0.81, 3.91) 1.79 (0.75, 4.25)18.5 to <25 204/363 1.00 1.0025 to <30 199/401 0.88 (0.69, 1.12) 0.84 (0.64, 1.11)

>30 109/260 0.75 (0.56, 0.99) 0.73 (0.53, 1.00)P Trend 0.013 0.018

BMI change <−5% (weight loss) 51/39 1.76 (1.08, 2.86) 1.29 (0.75, 2.21)

−5% to <+5% 107/144 1.00 1.005% to <15% 114/256 0.60 (0.43, 0.84) 0.66 (0.45, 0.95)15% to <25% 105/215 0.66 (0.47, 0.93) 0.64 (0.43, 0.94)25% to <35% 51/153 0.45 (0.30, 0.67) 0.41 (0.26, 0.65)

>35% 85/224 0.51 (0.36, 0.73) 0.55 (0.37, 0.82)P trend <0.001 <0.001

Average annual BMI change<0% 69/58 1.87 (1.22, 2.87) 1.46 (0.90, 2.36)

0 to <0.25% 106/167 1.00 1.000.25 to <0.5% 76 /173 0.69 (0.48, 1.00) 0.71 (0.47, 1.07)0.5 to <0.75% 82/160 0.81 (0.56, 1.16) 0.79 (0.53, 1.19)0.75 to <1% 55/135 0.64 (0.43, 0.95) 0.57 (0.36, 0.90)

≥ 1% 125/336 0.59 (0.43, 0.81) 0.63 (0.44, 0.91)P trend <0.001 <0.001

Adjustment variables: gender, smoking status, packAdjustment variables: gender, smoking status, pack--years, education, drinking, race, calories, and ageyears, education, drinking, race, calories, and age

Association between BMI, BMI change and UADT cancer stratified bAssociation between BMI, BMI change and UADT cancer stratified by gendery genderMale Females

Variables Ca/Co COR (95% CI) Adj OR1 (95% CI) Ca/Co COR (95% CI) Adj OR1 (95% CI)BMI at age 21

<20.34 57/96 1.00 1.00 54/159 1.00 1.0020.34 to <22.15 69/144 0.81 (0.52, 1.25) 1.06 (0.64, 1.75) 39/116 0.99 (0.61, 1.59) 0.90 (0.53, 1.52)22.15 to <24.34 132/180 1.24 (0.83, 1.84) 1.41 (0.88, 2.24) 21/84 0.74 (0.42, 1.30) 0.71 (0.38, 1.32)

≥24.34 123/200 1.04 (0.70, 1.54) 1.59 (1.00, 2.53) 18/53 1.00 (0.54, 1.85) 0.85 (0.43, 1.71)P Trend 0.367 0.017 0.617 0.482

BMI at baseline<18.5 kg/m2 3/4 0.89 (0.20, 4.03) 1.21 (0.23, 6.30) 10/9 3.68 (1.43, 9.51) 2.53 (0.89, 7.21)18.5 to <25 147/174 1.00 1.00 57/189 1.00 1.0025 to <30 158/296 0.63 (0.47, 0.85) 0.74 (0.53, 1.03) 41/105 1.29 (0.81, 2.07) 1.14 (0.68, 1.92)

>30 81/149 0.64 (0.45, 0.91) 0.71 (0.48, 1.06) 28/111 0.84 (0.50, 1.39) 0.74 (0.42, 1.30)P Trend 0.006 0.062 0.139 0.123

BMI change <−5% 35/24 1.57 (0.87, 2.85) 1.26 (0.64, 2.47) 16/15 2.75 (1.14, 6.64) 1.63 (0.63, 4.24)

−5% to <+5% 88/95 1.00 1.00 19/49 1.00 1.005% to <15% 89/176 0.55 (0.37, 0.80) 0.64 (0.41, 0.98) 25/80 0.81 (0.40, 1.61) 0.67 (0.32, 1.41)15% to <25% 78/142 0.59 (0.40, 0.89) 0.55 (0.35, 0.88) 27/73 0.95 (0.48, 1.90) 0.86 (0.41, 1.80)25% to <35% 37/92 0.43 (0.27, 0.70) 0.38 (0.22, 0.65) 14/61 0.59 (0.27, 1.30) 0.48 (0.20, 1.16)

>35% 54/91 0.64 (0.41, 1.00) 0.58 (0.35, 0.97) 31/133 0.60 (0.31, 1.16) 0.52 (0.25, 1.09)P trend .0005 <0.001 .001 .004

Average annual BMI change<0% 53/31 2.51 (1.49, 4.24) 2.04 (1.13, 3.69) 16/27 1.19 (0.53, 2.67) 0.81 (0.33, 1.97)

0 to <0.25% 85/125 1.00 1.00 21/42 1.00 1.000.25 to <0.5% 62/114 0.80 (0.53, 1.21) 0.83 (0.52, 1.32) 14/59 0.47 (0.22, 1.04) 0.39 (0.17, 0.91)0.5 to <0.75% 56/109 0.76 (0.49, 1.15) 0.71 (0.44, 1.16) 26/51 1.02 (0.50, 2.06) 0.82 (0.38, 1.78)0.75 to <1% 38/ 84 0.67 (0.41, 1.07) 0.55 (0.32, 0.96) 17/51 0.67 (0.31, 1.42) 0.51 (0.22, 1.18)

≥ 1% 87/155 0.83 (0.56, 1.21) 0.79 (0.51, 1.23) 38/181 0.42 (0.22, 0.79) 0.37 (0.18, 0.73)P trend <0.001 .003 0.002 .008

Adjustment variables: gender smoking status packAdjustment variables: gender smoking status pack years education drinking race calories and ageyears education drinking race calories and age

Loss Stable Gain P trendBMI at 21 Tertile 1

case/controls 8/1 29/37 123/306OR (95% CI)** 7.22 (0.79, 65.74 ) 1.00 0.60 (0.31, 1.14 ) 0.005

BMI at 21 Tertile 2case/controls 12/8 37/51 114/289OR (95% CI)** 1.52 (0.49, 4.74 ) 1.00 0.47 (0.27, 0.80 ) <0.001

BMI at 21 Tertile 3case/controls 31/30 41/55 118/253OR (95% CI)** 1.10 (0.52, 2.32 ). 1.00 0.68 (0.40, 1.15 ) 0.003

Never smokingcase/controls 14/12 26/72 118/403OR (95% CI)** 2.34 (0.90, 6.05 ) 1.00 0.82 (0.49, 1.38) 0.024

Former smokingcase/controls 30/15 51/42 184/300OR (95% CI)** 1.53 (0.65, 3.58 ) 1.00 0.56 (0.33, 0.94) 0.001

Current smokingcase/controls 7/12 30/29 53/145OR (95% CI)** 0.39 (0.11, 1.36 ) 1.00 0.31 (0.15, 0.66) 0.058

No Drinkingcase/controls 6/14 18/34 75/211OR (95% CI)** 0.54 (0.15, 1.93) 1.00 0.64 (0.32, 1.28) 0.622

Former Drinkerscase/controls 28/10 50/26 188/161OR (95% CI)** 1.18 (0.46, 3.01 ) 1.00 0.75 (0.42, 1.34) 0.169

Current Drinkerscase/controls 16/15 39/82 91/474OR (95% CI)** 2.19 (0.91, 5.31 ) 1.00 0.45 (0.27, 0.74 ) <0.001

Association of UADT cancer stratified by risk factors


Association of UADT cancer stratified by risk factors, contLoss Stable Gain P trend

Fruit and Vegetable intake

case/controls 18/10 31/40 115/205OR (95% CI)** 1.58 (0.55, 4.58 ) 1.00 0.75 (0.39, 1.41 ) 0.092

Quartile 2case/controls 7/5 26/37 82/216OR (95% CI)** 1.58 (0.38, 6.63 ) 1.00 0.44 (0.22, 0.87 ) 0.004



Timecase/controls 12/13 17/52 80/179OR (95% CI)** 2.61 (0.86, 7.88 ) 1.00 0.32 (0.17, 0.63 ) 0.889

Quartile 2case/controls 8/9 31/29 90/221OR (95% CI)** 0.46 (0.13, 1.62 ) 1.00 0.36 (0.19, 0.68) 0.016


Quartile 4case/controls 25/12 38/34 122/271OR (95% CI)** 1.54 (0.62, 3.87 ) 1.00 0.41 (0.23, 0.73 ) <0.001


Discussion for associations between BMI Discussion for associations between BMI change and lung and UADT cancerschange and lung and UADT cancers

BMI gain is inversely associated with UADT and lung BMI gain is inversely associated with UADT and lung cancers cancers Potential reasons includePotential reasons include–– Residual confoundingResidual confounding

However, adjusted for other smoking and drinking variablesHowever, adjusted for other smoking and drinking variables–– Reverse causalityReverse causality–– Biological mechanismBiological mechanism——Smoking/drinking, weight loss antiSmoking/drinking, weight loss anti--

oxidative pathwayoxidative pathway88--OHdG levels slightly higher in smokers than nonsmokersOHdG levels slightly higher in smokers than nonsmokers88--OHdG levels increase per unit decrease in BMI (OHdG levels increase per unit decrease in BMI (MizoueMizoue, , 2007)2007)Alcohol intake can induce free radical species in mice Alcohol intake can induce free radical species in mice leukocytesleukocytes

–– LowLow--BMIBMI--highhigh--waist circumference paradoxwaist circumference paradoxObservation that smokers and possibly alcohol drinkers, tend Observation that smokers and possibly alcohol drinkers, tend to have lower BMI but greater central adiposity.to have lower BMI but greater central adiposity.

Limitations, Strengths and ConclusionsLimitations– Self-reported measures of weight– No WHR– Measure at 1 year prior to interview may not be early

enoughStrengths– Large population-based sample size– the potential to adjust for a variety of smoking and

drinking measures. Conclusions– BMI gain is inversely associated with lung and UADT

cancers – This may be due to alterations in smoking and/or

drinking behaviors– BMI change may also serve as a potential indicator of

early tumor development among a smoking and/or alcohol drinking population.

Molecular approachMeasure inflammatory markersMeasure IGF1 and IGFBP3 levelsGenotype sometimes correlates to phenotype (Cheng I, 2007; Al-ZahraniA, 2006)

Calle EE, Kaaks R. Nature, 2004

In SummaryIn SummaryThe study of anthropometric measures The study of anthropometric measures is necessary in cancer.is necessary in cancer.These measures are fairly valid, costThese measures are fairly valid, cost--effective means to measure adiposity.effective means to measure adiposity.As of now weight maintenance is an As of now weight maintenance is an effective means of prevention against effective means of prevention against obesity related cancerobesity related cancer

Future directionsInvestigating genetic and biologic relationships Investigating genetic and biologic relationships between obesity and cancer would be beneficial.between obesity and cancer would be beneficial.For questionnaire design, it would be ideal to have more than 1 measure of adult weightOne could also look into changes in adult height Measures of WHR would assist in understanding Measures of WHR would assist in understanding the observed associations between BMI change the observed associations between BMI change and cancer.and cancer.

Thank you!Thank you!

Questions?Questions?

Weight change and Upper-aerodigestive tract (UADT) Cancers › epi › faculty › zhang › courses...

Documents

Transcript of Weight change and Upper-aerodigestive tract (UADT) Cancers › epi › faculty › zhang › courses...