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Journal Club: Tobacco and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Jiraboon Tosanguan

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Outline

• Introduction• Comparative Risk Assessment (CRA) for

smoking• Systematic Review and Meta-Analysis

on risk of lung cancer from tobacco.• Conclusion

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• Smoking has been causally associated with increased risk of premature mortality from lung cancer as well as other medical cause.

• Smoking in Thailand:– 9.49 million regular smokers (2007)– Male:Female ~ 23:1 (2007)– The majority is in the lower socioeconomic

status group

• Disease burden attributed by smoking can be an important input for policymakers to formulate strategies for improving population health and priority setting

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Comparative Risk Assessment

• “Systematic evaluation of the changes in population health which would result from modifying the population exposure to a risk factor.”

• The Population Attributable Fraction (PAF) approach is used.

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CRA Methods for Smoking

• Smoking Impact Ratio (SIR) Approach (Peto et al 1992)– Lung cancer mortality is an indicator of the

accumulative hazard of smoking and the ‘maturity’ of smoking epidemic in a population

– SIR can be used as ‘summarized’ prevalence.

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Systematic Review

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Papers identified through searches of Pubmed using keywords: “smoking AND "lung cancer” AND cohort AND risk” (n=729)

Evaluated in Details (n=32)

Excluded on basis of title and abstract if irrelevant, not about risk of LC from smoking etc. (n=695)

2 paper could not be obtained found

Excluded if1)No specific RR on Lung cancer (n=3)2)RR on LC but not comparing smokers and non-smoker (n=5)3)RR not sex-specific (n=1)4)Irrelevant (n=2)

Studies on risk of LC comparing smokers and non-smokers with sex-specific info (n=13)

Paper included in SR (M=9, FM=8, Total=10)

Excluded if data from the same cohort (n=2)

Meta-analysis performed using Review Manager 5

Included PaperReference Study Period No. of subjects

for analysisSource of subjects Event

followedCategory RR Confounding variables considered

Kenfield et al. 2010

1980-2004 102635 women

female US registered nurses aged 30-55 residing in 11 states

Mortality Female: Never Current Former

1 29.6 (24.0-36.5)6.31 (5.08-7.83)[HR]

age, history of hypertension, DM, high cholesterol, BMI, weight change, alcohol intake, physical activities, previous use of oral contraceptives, HRT, menopausal status, family history of MI

Freedman et al. 2008

1995-2003 279214 men, 184623 women

Members of American Association of Retired Persons, aged 50-71 residing in 8 states

Incidence Male CurrentFemale Current(According to dose)

20.7-54.913.4-47.3

Age, BMI, education, physical activities, alcohol intake, diet, pipe&cigar use, total energy intake.

Bae J-M et al. 2006

1993-2002 14272 men Male beneficiaries of the Korean Medical Insurance Corporation (KMIC)

incidence Male Current 4.18 (1.78-9.81) age, intake of coffee, raw fish and retinol.

Jee S H et al 2004

1992-2001 1212906 Koreans eligible for the KMIC

Mortality and incidence

Male Current (incidence)Male Current (Mortality)Female Current (Incidence)Female Current (Mortality)

4.0 (3.5-4.4)

4.6 (4.0-5.3)

2.2 (1.8-2.7)

2.5 (2.0-3.1)

age

Thun et al 1997(CPS-2)

1982-1988 1185106 friends, neighbours and acquaintances of ACS volunteers from 50 states, born between 1900-39.

mortality Male CurrentFemale Current

23.2 (19.3-27.9)12.8 (11.3-14.7)

age

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Included Paper

Reference Study Period

No. of subjects for analysis Source of subjects Event

followed Category RRConfounding

variables considered

Wakai K et al. 2007(Pooled analysis)

(4 studies)1983-2000

110002 men various cohorts from different parts of Japan

mortality Male Current 4.71 (3.76-5.89) age, and cohort

Huxley R et al 2007(Pooled Analysis)

31 studies(1966-1999)

480125 (83% Asian 34% female)

31 studies in Australia, NZ, China, Japan, Singapore, S Korea, Taiwan and other Asian countries.

Mortality Male Current (Asian)Male Current(ANZ)Female Current (Asian)Female Current (ANZ)

2.48 (1.99-3.11)

9.87 (6.04-16.12)

2.35 (1.29-4.28)

19.33 (10.0-37.3)

Wakai K et al. 2006(Meta-analysis)

22 studies(1958-2000)

8 cohorts (3 pop-based)14 case-control (all hosp-based)

Mortality and incidence

Male CurrentFemale Current

4.39 (3.92-4.92)2.79 (2.44-3.20)

Jacobs D R et al 1999(Pooled Analysis)

25 studies1964-1989

12763 men 16 cohorts in 9 countries (US, Finland, Holland, Italy, Croatia, Serbia, Greece, Japan)

Mortality Male: Current 1-9 >10

2.4 (1.40-4.08)6.5 (4.22-9.96)

age, residence, BMI, Cholesterol, BP, history of CHD.

Liu et al 1998(Retrospective proportional mortality study)

interviewed 1989-1991

family members of 1 million who died between 1986-8

98 areas of China (24 cities and 74 rural counties)

N/A Male Current>70Female Current>70

2.72 (0.05)2.47 (0.07)2.64 (0.08)2.50 (0.09)

age, resident

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• Results: Female

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• Results: Males

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Conclusion

• From the review, It has been observed about the differences between relative risk in US and Asian populations.

• The relative risks for lung cancer comparing current smokers and never-smokers were estimated to be 6.16 and 8.09 in male and female respectively.

• However, heterogeneity is high. Scope of meta-analysis may need to be reconsidered or alternative methods may be required.

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