Lung Cancer (2006) 53, 23—30

avai lab le at www.sc iencedi rec t .com

journa l homepage: www.e lsev ier .com/ locate / lungcan

Changes in the distribution of lung cancercell types and patient demography in adeveloping multiracial Asian country:Experience of a university teaching hospital

Chong-Kin Liam ∗, Yong-Kek Pang, Chai-Hooi Leow,Shyamala Poosparajah, Ashoka Menon

Division of Respiratory Medicine, Department of Medicine, University of Malaya Medical Centre, Faculty of Medicine,50603 Kuala Lumpur, Malaysia

Received 1 November 2005; received in revised form 6 March 2006; accepted 8 March 2006

KEYWORDSCell types;Changes;Distribution;Patient demography

Summary A comparison of patients with lung cancer diagnosed at the University of MalayaMedical Centre, Kuala Lumpur, Malaysia from October 1991 to September 1999 with anothergroup of lung cancer patients diagnosed at the same hospital during an earlier period of1967—1976 was undertaken to determine whether there had been a change in the distribu-tion of lung cancer cell types and patient demography. The number of histologically and/orcytologically proven lung cancer cases was 583 from October 1991 to September 1999 and 278from 1967 to 1976. The mean (S.D.) age of the patients during the period 1991—1999, 60.1(12.0) years was similar to that of patients during the period 1967—1976, 60.3 (12.2) years.There was no shift of the peak age distribution of lung cancer (i.e., the 7th decade) betweenthe two periods. In the recent period, the percentage of patients with adenocarcinoma hadincreased significantly to 43.2% from 25.2% while that of large cell carcinoma had decreased to3.3% from 11.9%. The percentages of patients with squamous cell carcinoma (SCC) and smallcell lung cancer remained stable. In the period 1967—1976, SCC was the commonest cell typein men and in smokers while adenocarcinoma was the commonest cell type in women and innever smokers. In the period 1991—1999, adenocarcinoma was the commonest cell type in bothmen and women as well as in smokers and never smokers.© 2006 Elsevier Ireland Ltd. All rights reserved.

∗ Corresponding author. Tel.: +603 7950 2299; fax: +603 7955 6396.E-mail addresses: liamck@ummc.edu.my, liamck@um.edu.my

(C.-K. Liam).

1. Introduction

Lung cancer is the most common cancer in the world since1985 and it is the most common cause of death from cancer[1]. It is the most common cancer in men worldwide and it is

0169-5002/$ — see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.lungcan.2006.03.009

24 C.-K. Liam et al.

the most common male cancer in the developing countries[1]. Every year, there are more than 1.3 million new casesof lung cancer worldwide with 49.9% of cases occurring inthe developing countries [1]. With the decline in smokingrates, the incidence of lung cancer has started to subside inthe developed countries but it is on the rise in the develop-ing world because of the continuously high smoking rate indeveloping countries [2]. Lung cancer is a rapidly growingproblem in many Asian countries [3]. In Malaysia, lung can-cer accounts for 13.8% of all cancers in males and 3.8% ofall cancers in females [4]. The male to female ratio in termsof incidence is 2.8.

In recent years, an increase in the incidence of lung ade-nocarcinoma at the expense of squamous cell carcinoma hasbeen observed worldwide [5]. There are important differ-ences between the epidemiology of lung cancer in the Westand in Asia such as the high incidence of adenocarcinoma innon-smoking Asian women [6]. Little has been published onthe distribution of lung cancer cell types and the changesthat had occurred over the years in developing countriesin Asia. The National Cancer Registry of Malaysia was onlyestablished in the year 2002 and there was no comprehen-sive statistics on lung cancer for the country before this.This study was undertaken to determine whether there hadbeen a recent change compared to an earlier period from1967 to 1976 in the distribution of lung cancer cell types andcharacteristics of patients with lung cancer diagnosed in the

Histological and cell typing from the biopsy and cytol-ogy specimens, respectively were classified according to theWorld Health Organisation classification for lung cancer. Theoriginal 1967 WHO classification [8] was used in the ear-lier period while the 1981 second edition [9] was used inthe latter period. Histological typing was used wheneveravailable. When there was disagreement between histolog-ical and cytological typing, histological typing was used.Non-small cell lung cancer that could not be subtyped byhistological and/or cytological examination was classified as‘undifferentiated’.

Smoking status of the patients was obtained from thecase records. For the 1967—1976 period, information wasonly available on whether the patient was ever a smokerirrespective of the intensity of smoking. For the 1991—1999period, when more detailed information on smoking wasavailable, smokers included current and ex-smokers whohad at least a one pack-year smoking history. Never smokersincluded those who had smoked not more than 100 cigarettesin their lifetime.

2.2. Statistical analysis

Simple descriptive statistics were used to describe the studypopulation. Categorical variables were compared using thechi-square (�2) test (with Yate’s correction) or Fisher’s exacttest when appropriate. For continuous variables, the stu-

University of Malaya Medical Centre (formerly known as theUniversity Hospital, Kuala Lumpur), a community teachinghospital in Kuala Lumpur, Malaysia.

2. Methods

2.1. Patients and methods

This was a retrospective review of patients with lung can-cer diagnosed at the University of Malaya Medical Centre,Kuala Lumpur, Malaysia from October 1991 to September1999 with comparison to a previously reported cohort oflung cancer patients diagnosed at the same hospital dur-ing an earlier period from 1967 to 1976 [7]. The Universityof Malaya Medical Centre, formerly known as the Univer-sity Hospital, is an 880-bed community teaching hospital.The hospital serves an urban and suburban population fromthe surrounding areas in Selangor, the most populous stateof the country, in which Kuala Lumpur, the national cap-ital city is situated. In addition, it also receives referralfrom the other states. The proportion of cases referred fromthe other states gradually declined from 1960s to 1990sas more medical centers were established in these otherstates.

All patients analysed had lung carcinoma suspected clin-ically and radiologically and proven by histological and/orcytological examination of specimens obtained at flexibleor rigid bronchoscopy; or other diagnostic procedures whichincluded sputum cytology, pleural fluid cytology, pleuralbiopsy, transthoracic needle aspiration or biopsy, open lungbiopsy, mediastinoscopy, and needle aspiration or biopsy ofan extrathoracic lesion such as a cervical lymph node. Allhistological and cytological confirmation was carried out inthe Department of Pathology of the hospital.

dent’s t-test was used to look at means. When appropriate,results of analysis were reported as odds ratios (OR) with95% confidence intervals (CI) and p-values. A p-value of lessthan 0.05 for a two-tailed test was considered statisticallysignificant. All analyses were performed using SPSS 11.0 forWindows (SPSS Inc., Chicago, IL, USA).

3. Results

3.1. Patient characteristics

Table 1 shows the characteristics of lung cancer patientsin the periods from 1967 to 1976 and from 1991 to 1999,respectively.

3.2. Age distribution

The number of histologically and/or cytologically confirmedlung cancer cases in this hospital during the period from 1967to 1976 was 278 and from October 1991 to September 1999was 583 (Table 1). The mean age of the patients during theperiod 1991—1999 was not significantly different from thatof patients during the period 1967—1976 (Table 1). Therewas also no shift in the age group of peak incidence of lungcancer (i.e., the 7th decade of life) between the two periods(Fig. 1).

3.3. Gender distribution

In the period 1967—1976, men constituted 70.5% of thepatients with a male to female ratio of 2.4 (Table 1). Themale to female ratio of lung cancer patients in the period1991—1999, 2.7, was not significantly different.

Changes in lung cancer cell types and patient demography 25

Table 1 Comparison of the characteristics of lung cancer patients in two different periods

Period p-Value OR (95% CI)

1967—1976 1991—1999

Number of patients 278 583Mean age (S.D.) (range) (year) 60.3 (12.2) (25—86) 60.1 (12.0) (21—90) 0.239

Gender (No. (%))Male 196 (70.5) 427 (73.2) 0.448 1.15 (0.82—1.59)Female 82 (29.5) 156 (26.8)

Smoking status (No. (%))Smoker 211 (75.9) 455 (78.0) 0.538 1.13 (0.79—1.60)Never smoker 67 (24.1) 128 (22.0)

Gender and smoking status (No. (%))Male

Smoker 169 (86.2) 393 (92.0) 0.034 1.85 (1.04—3.26)Never smoker 27 (13.8) 34 (8.0)

FemaleSmoker 42 (51.2) 62 (39.7) 0.119 0.63 (0.35—1.12)Never smoker 40 (48.8) 94 (60.3)

Cell type (No. (%))Adenocarcinoma 70 (25.2) 252 (43.2) <0.001Squamous cell 95 (34.1) 165 (28.3)Large cell 33 (11.9) 19 (3.3)Small cell 33 (11.9) 69 (11.8)Non-small cell (undifferentiated) 42 (15.1) 70 (12.0)Other 5 (1.8) 8 (1.4)

OR: odds ratio; CI: confidence interval.

3.4. Racial distribution

Malaysia has a multiracial population. Table 2 shows theracial composition of the general Malaysian population in1970 and 1991, population in the catchments of the hospitalin 1970 and 1991, patients aged 12 years and above attend-ing the hospital during the 1967—1976 period and 1991—1999period, and our lung cancer patients for both periods. Popu-lation data for 1970 and 1991 were used because populationcensus was carried out in these two years.

During the period from 1967 to 1976, the disproportion-ately large percentage of Chinese attending the hospital wasbecause compared to the other races, there was a higherpercentage of Chinese staying in urban and suburban areasof Malaysia at that time. In 1970, the percentage of Chinesein the population of the area served by the hospital, i.e., thecombined population of the state of Selangor and the capitalcity, 46.4% was significantly higher than that of 35.5% in thegeneral Malaysian population (OR, 1.57; 95% CI, 1.31—1.89;p < 0.001). During this period, the percentage of Chinese

Fig. 1 Age distribution of lung cancer patients in the two different periods.

26 C.-K. Liam et al.

Tabl

e2

Raci

aldi

stri

buti

onof

the

gene

ralM

alay

sian

popu

lati

on,

popu

lati

onin

area

serv

edby

the

hosp

ital

and

pati

ents

atte

ndin

gth

eho

spit

al,

and

lung

canc

erpa

tien

ts(%

)

Raci

algr

oup

Peri

od

1967

—19

7619

91—

1999

Gen

eral

popu

lati

on(1

970)

a[1

0]

Popu

lati

onin

area

serv

edby

the

hosp

ital

(197

0)a

[10]

Ove

rall

hosp

ital

atte

ndan

ceb

Lung

canc

erpa

tien

tsG

ener

alpo

pula

tion

(199

1)a

[11]

Popu

lati

onin

area

serv

edby

the

hosp

ital

(199

1)a

[11]

Ove

rall

hosp

ital

atte

ndan

ceb

Lung

canc

erpa

tien

ts

Mal

ay53

.034

.520

.211

.260

.543

.840

.919

.0Ch

ines

e35

.546

.449

.180

.928

.239

.928

.470

.7In

dian

10.6

18.3

29.0

6.1

7.9

15.6

26.8

8.9

Oth

er0.

90.

81.

71.

83.

40.

73.

91.

4a

For

the

year

stat

ed.

bAv

erag

efo

rth

epe

riod

stat

edfo

rpa

tien

tsag

ed12

year

san

dab

ove.

among the overall attendance of the hospital (49.1%) was notsignificantly different from that in the population of the areaserved by the hospital (46.4%) (OR, 1.11; 95% CI, 0.93—1.33;p = 0.244). However, the percentage of Chinese among thelung cancer patients (80.9%) was significantly higher thanthat among the population of the area served by the hospi-tal (46.4%) (OR, 4.89; 95% CI, 3.98—6.01; p < 0.001) as wellas significantly higher than that among the overall atten-dance of the hospital (49.1%) (OR, 4.39; 95% CI, 3.58—5.39;p < 0.001). The percentage of Malays among the lung cancerpatients (11.2%) was significantly lower than the percentageof Malays in the population of the area served by the hospi-tal (34.5%) (OR, 0.24; 95% CI, 0.19—0.31; p < 0.001) and alsosignificantly lower than the percentage of Malays among theoverall attendance of the hospital (20.2%) (OR, 0.50; 95%CI, 0.39—0.64; p < 0.001). Similarly, the percentage of Indi-ans among the lung cancer patients (6.1%) was significantlylower than the percentage of Indians in the population ofthe area served by the hospital (18.3%) (OR, 0.29; 95% CI,0.21—0.40; p < 0.001) and also significantly lower than thepercentage of Indians among the overall attendance of thehospital (29.0%) (OR, 0.16; 95% CI, 0.12—0.22; p < 0.001).

There was a significant increase in the percentage ofMalay patients attending the hospital from 20.2% in the1967—1976 period to 40.9% in the 1991—1999 period (OR,2.73; 95% CI, 2.23—3.35; p < 0.001) (Table 2). There was asignificant decrease in the percentage of Chinese patientsattending the hospital from 49.1% in the 1967—1976 periodt0Miiabip9co4

ni1pnc0tth

3

Twmbs1

o 28.4% in the 1991—1999 period (OR, 0.41; 95% CI,.34—0.50; p < 0.001). The overtaking of the Chinese by thealays as the largest racial group attending the hospital

n the 1991—1999 period could be attributed to an overallncrease in percentage of Malays in the general populationnd a gradual rural to urban migration of Malays over timeecause of socioeconomic reasons. There was a significantncrease in the percentage of Malays in the general Malaysianopulation from 53.0% in 1970 to 60.5% in 1991 (OR, 1.36;5% CI, 1.13—1.63; p = 0.001). Similarly, there was a signifi-ant increase in the percentage of Malays in the populationf the area served by the hospital from 34.5% in 1970 to3.8% in 1991 (OR, 1.48; 95% CI, 1.23—1.78; p < 0.001).

In both periods, the lung cancer patients were predomi-antly Chinese (Table 2). There was a significant increasen the percentage of Malay lung cancer patients from1.2% in the 1967—1976 period to 19.0% in the 1991—1999eriod (OR, 1.86; 95% CI, 1.43—2.41; p < 0.001), and a sig-ificant decrease in the percentage of Chinese lung can-er patients in the 1991—1999 period (OR, 0.57; 95% CI,.46—0.71; p < 0.001). This change could be explained byhe changes in the racial distribution of the population ofhe area served by the hospital and of patients attending theospital.

.5. Smokers versus never smokers

he percentages of lung cancer patients who were smokersere similar for both periods (Table 1). The overwhelmingajority of male lung cancer patients were smokers inoth periods. The percentage of male patients who weremokers had increased significantly from 86.2% in the967—1976 period to 92% in the 1991—1999 period while

Changes in lung cancer cell types and patient demography 27

Table 3 Smoking status and major lung cancer cell types in the two different periods

Cell type(No. (%))

Period p-Value OR (95% CI)

1967—1976 (n = 278) 1991—1999 (n = 583)

Smoker(n = 211)

Neversmoker(n = 67)

Smoker:neversmoker ratio

Smoker(n = 455)

Neversmoker(n = 128)

Smoker:neversmoker ratio

Adenocarcinoma 43 (20.4) 27 (40.3) 1.6 163 (35.8) 89 (69.5) 1.8 0.718 1.15 (0.64—2.05)Squamous cell 81 (38.4) 14 (20.9) 5.8 153 (33.6) 12 (9.4) 12.8 0.086 2.20 (0.91—5.37)Small cell 30 (14.2) 3 (4.5) 10.0 68 (14.9) 1 (0.8) 68.0 0.098 6.80 (0.59—177.10)Large cell 24 (11.4) 9 (13.4) 2.7 16 (3.5) 3 (2.3) 5.3 0.499 2.00 (0.40—11.11)

OR: odds ratio; CI: confidence interval.

the percentage of female patients who were smokers didnot change significantly (Table 1).

Females were over-represented in the groups of neversmokers with lung cancer in both periods (Table 1). In the1967—1976 period, the proportion of never smokers whowere females [40/67 (59.7%)] was significantly higher thanthe proportion of male patients who were never smokers[27/67 (40.3%)] (OR, 2.73; 95% CI, 2.23—3.35; p = 0.038).In the 1991—1999 period, the proportion of never smokerswho were females [94/128 (73.4%)] was also significantlyhigher than the proportion of male patients who were neversmokers [34/128 (26.6%)] (OR, 7.64; 95% CI, 4.24—13.87;p < 0.001).

3.6. Distribution of lung cancer cell types

Compared to the 1967—1976 period, the percentage ofpatients with adenocarcinoma in the 1991—199 period hadincreased significantly to 43.2% from 25.2% while that oflarge cell carcinoma (LCC) in the 1991—1999 period haddecreased significantly to 3.3% from 11.9% (Table 1). Thepercentages of patients with squamous cell carcinoma (SCC)and small cell lung cancer (SCLC) remained stable.

3.7. Smoking status and major lung cancer celltypes

ers and adenocarcinoma was the most frequent cell typeamong never smokers. However, in the 1991—1999 period,adenocarcinoma was the most common cell type in bothsmokers and never smokers. In both periods, the associationwith smoking was strongest for SCLC and SCC. The ratio ofsmokers to non-smokers was the lowest for adenocarcinomaand this had not changed significantly from the 1967—1976period to the 1991—1999 period. The percentage of adeno-carcinoma patients who were smokers was 61.4% (43/70) inthe 1967—1976 period and 64.7% (163/252) in the 1991—1999period. Although there was a trend to a stronger associationof both SCLC and SCC with smoking in the 1991—1999 period,the difference from that seen in the 1967—1976 period didnot reach statistical significance. The shift in the distribu-tion of cell type between the two periods was therefore, notdue to a change in the rates of smoking among patients withthe various lung cancer cell types.

3.8. Gender, smoking status and lung cancer celltypes

Table 4 shows the gender of the patients and main lungcancer cell types for the two periods. In the 1967—1976period, SCC was the commonest cell type in men while ade-nocarcinoma was the commonest cell type in women. Inthe 1991—1999 period, adenocarcinoma was the common-est cell type in both male and female patients. For the1wsp

diff

1—1

le427

(37.(32.(13.

6 (3.

Table 3 shows the smoking status of the patients and mainlung cancer cell types for the two periods. In the 1967—1976period, SCC was the most frequent cell type among smok-

Table 4 Gender and major lung cancer cell types in the two

Cell type(No. (%))

Period

1967—1976 (n = 278) 199

Male(n = 196)

Female(n = 82)

Male:femaleratio

Ma(n =

Adenocarcinoma 45 (23.0) 25 (30.5) 1.8 159Squamous cell 71 (36.2) 24 (29.3) 3.0 139Small cell 25 (12.8) 8 (9.8) 3.1 56Large cell 23 (11.7) 10 (12.2) 2.3 1

OR: odds ratio; CI: confidence interval.

967—1976 period, the male to female ratios of patientsith the different major cell types of lung cancer were not

ignificantly different (p = 0.463) while for the 1991—1999eriod, the male to female ratio of patients with adenocarci-

erent periods

p-Value OR (95% CI)

999 (n = 583)

)Female(n = 156)

Male:femaleratio

2) 93 (59.6) 1.7 0.966 0.95 (0.53—1.71)6) 26 (16.7) 5.4 0.087 1.81 (0.93—3.53)1) 13 (8.3) 4.3 0.712 1.38 (0.45—4.15)7) 3 (1.9) 5.3 0.328 2.32 (0.47—12.72)

28 C.-K. Liam et al.

Table 5 Major lung cancer cell types according to gender and smoking status of patients in the two periods

Cell type Gender p-Value OR (95% CI)

Male Female

Smoker Neversmoker

Smoker:neversmoker ratio

Smoker Neversmoker

Smoker:neversmoker ratio

1967—1976Adenocarcinoma 34 11 3.1 9 16 0.6 0.003 5.49 (1.69—18.48)Squamous cell 65 6 10.8 16 8 2.0 0.008 5.42 (1.43—21.04)Small cell 24 1 24.0 6 2 3.0 0.139 8.00 (0.44—271.78)Large cell 19 4 4.8 5 5 1.0 0.090 4.75 (0.71—34.83)

1991—1999Adenocarcinoma 137 22 6.2 26 67 0.4 <0.001 16.05 (8.10—32.12)Squamous cell 135 4 33.8 18 8 2.3 <0.001 15.00 (3.59—67.20)Small cell 55 1 55.0 13 0 ∞ 1.000 0.00 (0.00—79.93)Large cell 15 1 15.0 1 2 0.5 0.077 30.00 (0.83—5793.86)

OR: odds ratio; CI: confidence interval.

noma was significantly lower than the other major cell types(p < 0.001). However, the male to female ratios of patientswith the different cell types of lung cancer did not changesignificantly between the two periods. Table 5 shows themajor lung cancer cell types according to the gender andsmoking status of the patients for the two periods. In men,adenocarcinoma was associated with smoking although lessstrongly so compared to SCC, SCLC and LCC in both periods.For both periods, the majority of females with adenocar-cinoma were never smokers. In the 1967—1976 period, 16(64.0%) of the 25 females with adenocarcinoma were neversmokers while in the 1991—1999 period, 67 (72.0%) of the93 females with adenocarcinoma were never smokers (OR,1.45; 95% CI, 0.51—4.04; p = 0.593).

3.9. Age of patients according to gender, smokingstatus and lung cancer cell type in the 1991—1999period

The mean age (S.D.) of the lung cancer patients in the1991—1999 period was 60.1 (12.0) years. Although the meanage (S.D.) of female patients at 58.7 (13.0) years wasyounger than that of the male patients [60.6 (11.6) years]the difference was not statistically significant (mean differ-ence, 2.0 years; 95% CI, −0.2 to 4.1 years; p = 0.083). Neversmokers [mean (S.D.) age, 54.7 (14.5) years] were signifi-cantly younger than smokers [mean (S.D.) age, 61.6 (10.7)ypya9sc(y

wyw

noma were significantly younger than those with other celltypes (mean difference, 3.4 years; 95% CI, 1.4—5.3 years;p = 0.001).

4. Discussion

In this study conducted in a university teaching hospital inMalaysia, we have shown that in the 1990s, the proportion oflung cancer of the adenocarcinoma cell type had increasedsignificantly while that of LCC had decreased compared tothe 1960s and 1970s. The proportions of lung cancer of squa-mous cell and small cell types, however, had remained stableover this period. This shift in the distribution of histologi-cal cell types in which adenocarcinoma is becoming moreprevalent has been noted worldwide [5]. Our study showedthat in the more recent period, adenocarcinoma had becomethe commonest cell type in both male and female patientsas well as in smokers and never smokers. A recent MayoClinic series has similarly demonstrated that adenocarci-noma is the most frequent histological subtype regardlessof the patient’s gender or smoking status [12].

Better pathological methods for typing cancers and diag-nostic advances such as improved stains for detecting mucinin adenocarcinoma in recent years as well as revision of theWHO classification could have resulted in a decrease in theproportion of cancers classified as undifferentiated and alsoresulted in many tumours formerly classified as large cellcHdvonias[omt

ears] (mean difference, 6.9 years; 95% CI, 4.6—9.2 years;< 0.001). Male never smokers [mean age (S.D.), 53.9 (15.9)ears] were significantly younger than male smokers [meange (S.D.), 61.2 (10.9) years] (mean difference, 7.2 years;5% CI, 3.2—11.2 years; p < 0.001). Similarly, female nevermokers [mean age (S.D.), 55.0 (14.1) years] were signifi-antly younger than female smokers [mean age (S.D.), 64.28.9) years] (mean difference, 9.2 years; 95% CI, 5.2—13.1ears; p < 0.001).

The mean age (S.D.) of patients with adenocarcinomaas 58.2 (13.2) years, patients with SCC was 62.8 (9.7)ears, patients with SCLC was 62.8 (10.2) years and patientsith LCC was 61.6 (13.2) years. Patients with adenocarci-

arcinoma being now classified as adenocarcinoma [13—16].owever, most observers do not feel that the changes iniagnostic practices and classification of lung cancers pro-ide the full explanation for the shift in cell type distributionver time [17,18] and others have shown that the rise in ade-ocarcinoma incidence in the West antedated the diagnosticnnovations [19]. This trend of increase in adenocarcinomat the expense of SCC has been attributed to the switch frommoking high-tar to low-tar filtered cigarette over the years19—21]. To compensate for the low tar and nicotine yieldf the cigarettes smokers change their smoking pattern toore frequent and deeper inhalation apart from increasing

he number of cigarettes they smoke. More intense smoking

Changes in lung cancer cell types and patient demography 29

and deeper inhalation of tobacco smoke and higher deliv-ery of carcinogens such as nitrogen oxides and nitrosatedcompounds which are found in larger amounts in filteredcigarettes to the lung periphery are thought to be the causeof the increasing incidence of adenocarcinomas in smokers[22,23].

The change in the distribution of lung cancer cell typesin our patients over the two periods was unlikely to be dueto a change in the smoking rate in our patients since theproportions of our lung cancer patients during the two peri-ods who smoked were similar although for pragmatic reasonsthe criteria for defining smoking status were slightly differ-ent in the two periods. This shift in the distribution of celltypes might be due to a switch to smoking low-tar filteredcigarette over the years as explained by others [19—21].However, changes in cigarette design and smoking behaviourcould not have account for the increased incidence of ade-nocarcinoma in our non-smoking patients and in our femalepatients the majority of whom were never smokers. Pas-sive inhalation of sidestream smoke from cigarettes has beenproposed as a risk factor for adenocarcinoma in non-smokersbecause sidestream smoke, which contains many gaseouscomponents, can reach the deeper parts of the lung morereadily than can mainstream smoke which contains moreparticulates [24]. As information on passive smoking was notroutinely elicited from our patients and inadequately docu-mented, we were not able to determine whether exposure toenvironmental tobacco smoke in our non-smoking patients

pital in the two periods is noteworthy. Even during the periodfrom 1991 to 1997 when the Malays constituted the largestracial group attending the hospital, lung cancer was stillmost common among the Chinese. Furthermore, statisticsfrom the national cancer registry which was started in theyear 2002 show that the age-standardised incidence of lungcancer for the Chinese is more than twice that of the Malaysand Indians for both sexes [4]. The Chinese was also reportedto be the predominant racial group with lung cancer in Sin-gapore which has a multiracial population comprising ofChinese, Malays and Indians like Malaysia [30]. The reasonfor this racial difference in predisposition to lung cancer isunclear. It is possible that environmental risk factors, suchas diet, may condition the risk in the Chinese, or perhapsthere are racial differences in the way in which tobacco ismetabolised as suggested by Wagenknecht et al. [31].

Our data from the 1991—1999 period showed that in bothmales and females, never smokers were diagnosed with lungcancer at a significantly younger mean age than smokers.Other authors had also reported that non-smokers were diag-nosed to lung cancer at a mean age which was younger thanthat of smokers in Asian countries like Japan, Taiwan, HongKong and Singapore [6,26,32,33]. This is in contrast to West-ern populations where smokers are more likely to have lungcancer at a younger age than non-smokers because of thedose-response relationship between smoking exposure andlung cancer [34]. In addition, our patients with adenocarci-noma were diagnosed to have the disease at a younger agetan[

actt

5

Ihlplhpostaistna

R

could have contributed to the shift of cell types.For the year 2000, it is estimated that 85% of lung cancer

in men and 47% of lung cancer in women is the consequenceof tobacco smoking [1]. The smoking prevalence rates in theMalaysian population based on a 1996 survey are 49.2% formale subjects and 3.5% for female subjects aged 18 yearsand above [25]. The overwhelming majority of our male lungcancer patients were smokers and the percentage of smok-ers among our male patients had increased in the recentperiod. Our female patients constituted about 60—70% ofour patients who were never smokers. It has been notedby others that women are considerably over-representedin the group of non-smokers with lung cancer particularlyin Asian populations [6,26]. In our patients, the associationwith smoking was the strongest for SCLC and SCC and muchless pronounced for adenocarcinoma and this association hasbeen well described in the literature [27,28]. However, ourdata for both the periods showed there were gender dif-ferences. While the association with smoking was true forSCLC, SCC, LCC and adenocarcinoma in our male patients; itwas true only for SCLC and SCC in our female patients as themajority of our female adenocarcinoma patients were neversmokers. Even though adenocarcinoma is the most commoncell type in non-smokers, it is estimated that 86% of adeno-carcinomas are caused by cigarette smoking [29]. However,only slightly more than 60% of our patients with adenocar-cinoma in both periods were smokers. The high incidenceof female non-smokers with adenocarcinoma often seenonly in the Asian population has been reported by others[6].

The disproportionately high proportion of our lung cancerpatients who were Chinese compared to the racial compo-sition of the urban and suburban population served by thehospital and racial breakdown of patients attending our hos-

han those with the other lung cancer cell types. This is ingreement with other studies which show that adenocarci-oma is the predominant cell type among younger patients11,21,33,35].

A high percentage of non-smoking female patients withdenocarcinoma and a younger age of diagnosis of adenocar-inoma and in non-smokers suggest that risk factors otherhan active smoking may be involved in carcinogenesis inhese patients and in lung adenocarcinoma.

. Conclusion

n conclusion, the mean age of patients with lung cancerad not changed and the age group of peak incidence ofung cancer remained the 7th decade of life for the twoeriods. Compared to the racial composition of the popu-ation served by our hospital and of patients attending theospital, a disproportionately high percentage of Chineseatients with lung cancer was observed during both peri-ds. Females were over-represented in the groups of nevermokers with lung cancer in both periods. In recent years,he proportion of cases of adenocarcinoma had increasednd adenocarcinoma had become the commonest cell typen both men and women as well as in smokers and nevermokers. Patients with adenocarcinoma were younger thanhose with other cell types. Lung cancer was diagnosed inever smokers at a younger age than smokers in both malesnd females.

eferences

[1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002. CA Cancer J Clin 2005;55:74—108.

30 C.-K. Liam et al.

[2] Boffetta P, Parkin DM. Cancer in developing countries. CA Can-cer J Clin 1994;4:81—91.

[3] Yang SP, Luh KT. Primary lung cancer in Asia. Bronchus1986;2:6—8.

[4] Second Report of the National Cancer Registry, Cancer inci-dence in Malaysia, 2003, National Cancer Registry, Malaysia(http://www.crc.gov.my/ncr).

[5] Rivera MP, Detterbeck FC, Loomis DP. Epidemiology and classi-fication of lung cancer. In: Detterbeck FC, Rivera MP, SocinskiMA, Rosenma JG, editors. Diagnosis and treatment of lungcancer. 1st ed. Philadelphia: WB Saunders Co.; 2001. p. 45—72.

[6] Koo LC, Ho JH. Worldwide epidemiological patterns of lung can-cer in nonsmokers. Int J Epidemiol 1990;19:S14—23.

[7] Menon MA, Saw HS. Lung cancer in Malaysia. Thorax 1979;34:269—73.

[8] World Health Organization: histological typing of lung tumours.1st ed Geneva: World Health Organization; 1967.

[9] World Health Organization: histological typing of lung tumours.2nd ed. Geneva: World Health Organization; 1981.

[10] Social Statistics Bulletin, Peninsular Malaysia, 1978—1979,Department of Statistics, Malaysia 1978—1979.

[11] Social Statistics Bulletin, Malaysia 1991, Department of Statis-tics, Malaysia 1991.

[12] Yang P, Allen MS, Aubry MC, Wampfler JA, Marks RS, EdellES, et al. Clinical features of 5,628 primary lung cancerpatients: experience at Mayo Clinic from 1997 to 2003. Chest2005;128:452—62.

[13] Wu AH, Henderson BE, Thomas DC, Mack T. Secular trends inhistologic types of lung cancer. J Natl Cancer Inst 1986;77:

[

[

[

[

[

[19] Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, HeathJr CW. Cigarette smoking and changes in the histopathology oflung cancer. J Natl Cancer Inst 1997;89:1580—6.

[20] Levi F, Franceschi S, La Vecchia C, Randimbison L, Te VC.Lung cancer trends by histologic type in Vaud and Neuchatel,1974—1994, Switzerland. Cancer 1997;79:906—14.

[21] Kreuzer M, Kreienbrock L, Muller KM, Gerken M, WickmannE. Histologic types of lung cancer and age at onset. Cancer1999;85:1958—65.

[22] Hoffman D, Rivenson A, Hecht SS. The biological significance oftobacco-specific N-nitrosamines, smoking and adenocarcinomaof the lung. Crit Rev Toxicol 1996;26:199—221.

[23] Wynder EL, Muscat JE. The changing epidemiology of smok-ing and lung cancer histology. Environ Health Perspect1995;103:143—8.

[24] Wynder EL, Goodman MT. Smoking and lung cancer: some unre-solved issues. Epidemiol Rev 1983;5:177—207.

[25] Report of the Second National Health and Morbidity Survey,Public Health Institute, Ministry of Health, Malaysia, 1997.

[26] Tok CK, Wong EH, Lim WT, Leong SS, Fong KW, Wee J, et al.The impact of smoking status on the behavior and survival out-come of patients with advanced non-small cell lung cancer: aretrospective analysis. Chest 2004;126:1750—6.

[27] Lubin JH, Blot WJ. Assessment of lung cancer risk factors byhistologic category. J Natl Cancer Inst 1984;73:383—9.

[28] Holmes EC. Lung cancer. In: Simmons DH, editor. Current Pul-monology. Boston, Mass: Houghton Miffin; 1979. p. 239—50.

[29] Brownson RC, Chang JC, Davis JR. Gender and histologic typevariations in smoking-related risk of lung cancer. Epidemiology1992;3:61—4.

[

[

[

[

[

[

53—6.14] Kung ITM, So KF, Lam TH. Lung cancer in Hong Kong Chi-

nese: mortality and histological types, 1973—1982. Br J Cancer1984;50:381—8.

15] Vincent RG, Pickren JW, Lane WW, Bross I, Takita H, Houten L,et al. The changing histopathology of lung cancer: a review of1682 cases. Cancer 1977;39:1647—55.

16] Ikeda T, Kurita Y, Inutsuka S, Tanaka K, Nakanishi Y, ShigematsuN, et al. The changing pattern of lung cancer by histologi-cal type—–a review of 1151 cases from a university hospitalin Japan, 1970—1989. Lung Cancer 1991;7:157—64.

17] Churg A. Lung cancer cell type and occupational exposure. In:Samet JM, editor. Epidemiology of lung cancer. New York, NY:Marcel Dekker; 1994. p. 413—36.

18] Charloux A, Quoix E, Wolkove N, Small D, Pauli G, KreismanH. The increasing incidence of lung adenocarcinoma: realityor artefact? A review of the epidemiology of lung adenocarci-noma. Int J Epidemiol 1997;26:14—23.

30] Shanmugaratnam K. Epidemiological studies of lung cancer inSingapore. In: Hirayama T, editor. Cancer in Asia. Baltimore:University Park Press; 1976. p. 153.

31] Wagenknecht LE, Cutter GR, Haley NJ, Sidney S, Manolio TA,Hughes GH, et al. Racial differences in serum cotinine lev-els among smokers in the coronary artery risk development in(young) adults study. Am J Public Health 1990;80:1053—6.

32] Sekine I, Nishiwaki Y, Yokose T, Nagai K, Suzuki K, Kodama T.Young lung cancer patients in Japan: different characteristicsbetween the sexes. Ann Thorac Surg 1999;67:1451—5.

33] Tsai CM, Perng RP, Huang WL. Lung cancer in young Chinese.Cancer Detect Prev 1988;11:235—8.

34] Loeb LA, Ernster VL, Warner KE, Abbotts J, Laszlo J. Smok-ing and lung cancer: an overview. Cancer Res 1984;44:5940—58[Erratum in Cancer Res, 1986; 46:5453].

35] Kuo CW, Chen YM, Chao JY, Tsai CM, Perng RP. Non-smallcell lung cancer in very young and very old patients. Chest2000;117:354—7.