Lung Cancer 78 (2012) 16–22

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Lung Cancer
journal homepage: www.elsevier.com/locate/lungcan

Rising incidence of adenocarcinoma of the lung in Canada

XiaoHong Jiang a , Margaret de Groh a,∗ , Shiliang Liu b , Hongbo Liang c , Howard Morrison a
a
Science Integration Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Canada
b
Health Surveillance and Epidemiology Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Canada
c
Chronic Disease Surveillance and Monitoring Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Canada

a r t i c l e i n f o a b s t r a c t

Article history: Background/aims: This study examines temporal trends in incidence of lung cancer in 1972–2007, tem-
Received 19 January 2012 poral trends in histological types of lung cancer in 1988–2007, and age–period–cohort effects on the
Received in revised form 17 April 2012 incidence rates of lung cancer in Canada.
Accepted 2 June 2012
Methods: Using incidence data for 1972–2007, we calculated the three-year period rates and annual
percentage change (APC): from 1988 to 2007 we were able to do this by histological types. We used
Keywords:
age–period–cohort modelling to estimate underlying effects on the observed trends in incidence of
Lung cancer
adenocarcinoma of the lung.
Incidence of adenocarcinoma
Cigarette smoking
Results: In Canada, age-adjusted incidence rates have increased by 263% in women and 4% in men from
Age–period–cohort modelling 1972 to 2007. Annual percent change in age-adjusted rates for women by histological type from 1988
to 2007 were 2.2% for adenocarcinoma, −0.9% for squamous cell carcinoma and −0.4% for small cell car-
cinoma. Age-adjusted rates decreased for men over the same 20 years: adenocarcinoma (APC: −0.6%),
squamous cell carcinoma (APC: −4.2%) and small cell carcinoma (APC: −3.2%) in men. Age-specific inci-
dence rates increased most rapidly for adenocarcinoma in those aged 75+ years (APC: women 4.3%;
APC: men 1.1%). The age–period–cohort modelling suggested that the risk of being diagnosed with
adenocarcinoma is decreasing in men and will be decreasing slowly in women.
Conclusions: The adenocarcinoma incidence trends observed are consistent with smoking trends, how-
ever, the relative risk with smoking is lower for adenocarcinoma than for squamous cell carcinoma and
small cell carcinoma. This suggests that other exposures may play a role in adenocarcinoma incidence,
such as exposure to environmental carcinogens.
Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction in exposure to environmental carcinogens [10,11]. Though there

Lung cancer is the leading cause of cancer death in both men
(28.0%) and women (27.0%) in Canada [1]. Incidence of lung cancer
continues to increase in women and decrease in men. Patterns of
histological types of lung cancer have also changed in the United
States and Canada [2–4]. Adenocarcinoma has become the most
commonly diagnosed type of lung cancer in women and men in
the United States. In contrast, squamous cell carcinoma remains
the predominant cell type in Europe [5] and was the most frequent
histological subtype in women during the study period, 1988–2007.
The changing patterns of lung cancer incidence rates by histo-
logical type have been attributed to decreased smoking rate and
changes in the types of cigarettes smoked [6–9] as well as changes
∗ Corresponding author at: Science Integration Division, Centre for Chronic Dis-
ease Prevention and Control, Public Health Agency of Canada, 7th Floor, 785 Carling
Ave, Ottawa, ON K1A 0K9, Canada. Tel.: +1 613 957 1786; fax: +1 613 941 5497.
E-mail address: Margaret.deGroh@phac-aspc.gc.ca (M. de Groh).
have been no reports on the trends in the histological types of lung
cancer in Canada, a recent report found that the rate of incidence
of lung cancer in the province of Alberta had increased between
1979 and 1998 and that the trends in histological type had also
changed [2].
The aims of this study were to (1) analyse the temporal trends in
incidence of lung cancer in Canada from 1972 to 2007, (2) examine
the changes in incidence of histological types from 1988 to 2007,
and (3) used age–period–cohort modelling to assess the potential
underlying effects on the incidence of lung cancer.
2. Materials and methods
Lung cancer incidence data for 1972–1992 were obtained from
the National Cancer Incidence Reporting System (NCIRS) and for
1992–2007 from the Canadian Cancer Registry (CCR) of Statis-
tics Canada. A detailed description of the registry, including data
sources, methodology, and accuracy, is available on the Statistics
Canada website [12]. Before 1992, types of lung cancer were coded

0169-5002/$ – see front matter. Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.lungcan.2012.06.002
 X. Jiang et al. / Lung Cancer 78 (2012) 16–22
120
100
Incidence rate per 100 000
80
60
40
20
Years
Fig. 1. Age-adjusted incidence rates of lung cancer by sex, Canada, 1972–2007.
according to the International Classification of Diseases, Ninth
Revision (ICD-9), and from 1992 according to the International
Classification of Diseases for Oncology, Third Edition (ICD-O-3)
[13]. We categorized the cases of lung cancer into three major
types: adenocarcinoma (M8140, 8211, 8230–8231, 8250–8260,
8323, 8480–8490, 8550–8560, 8570–8572), squamous cell car-
cinoma (M8050–8076), small cell carcinoma (M8040–8045), as
well as other and unknown types [2,14]. In total, there were
385,469 cases of invasive lung and bronchus cancer (ICD-O-3 C34)
between 1988 and 2007: 50,233 (32.9%) cases of adenocarcinomas,
22,290 (14.6%) of squamous cell carcinomas, and 20,318 (13.3%)
of small cell carcinomas in women, and 56,907 (24.4%) cases of
adenocarcinomas, 59,613 (25.6%) of squamous cell carcinomas, and
27,622 (11.9%) of small cell carcinomas in men. Cases of other and
unknown types of lung cancer were 39.2% in women and 38.2% in
men.
First, the average 3-year age-adjusted incidence rates for the
period 1988–1990 were contrasted with that for 2005–2007, for
men and women separately. The incidence rates by histologi-
cal type were then compared for six specific age groups 35–44,
45–54, 55–64, 65–74, 75–85+, 0–85+ years. Temporal trends in
the incidence of lung cancer by histological type were evaluated
through linear regression models using logarithms of the annual
age-standardized rates for all ages as well as for the six age groups.
The annual percentage changes (APC) for histological types dur-
ing the study period were derived from the regression coefficients
to demonstrate the differences in the periods 1988–1990 and
2005–2007. All age-adjusted incidence rates were calculated using
the 1991 Canadian population data as the standard [15].
To analyse the time trends in adenocarcinoma of the lung cancer
incidence in more detail, an age–period–cohort model was fitted to
the data [16]. In analyses integrating age at diagnosis, time period of
diagnosis, and birth cohort, age was grouped into 12 five-year age
groups (25–29, 30–34, 35–39, 40–44, 45–49, 50–54, 55–59, 60–64,
65–69, 70–74, 75–79, and 80–84 years), and 4 five-year time peri-
ods (1988–1992, 1993–1997, 1998–2002 and 2003–2007). Based
on the period and age groups, we calculated 15 overlapping 10-year
birth cohorts.
A Poisson regression model was used to estimate the age, period,
and cohort effects in adenocarcinoma. The model assumes that the
number of cancer cases follows a Poisson distribution and the inci-
dence rates are a multiplicative function of the model parameters,
making the logarithm of the rates an additive function of the
17
Male
Female
parameters [17,18]. For example, the form of the
age–period–cohort model was given by
 
dij
log =  + ˛i + ˇj + k
pij
where log(dij /pij ) is the rate of interest with dij denoting the num-
ber of the cases in the ith age group and jth period and pij is the
population at risk in the ith age group and jth period;  is the
intercept term; ˛i is the effect of the ith age group; ˇj is the effect
of jth period category; and  k is the effect of the kth cohort cat-
egory (k = I − i + j when i = 1, 2, . . ., I). Inherent in the three-factor
age–period–cohort model is the well-known non-identifiability
problem: parameters for age, period, and cohort cannot be uniquely
estimated because of the exact linear dependence of the regression
variables (cohort = period − age) [19,20].
Age, period, and birth cohort for each sex were first evaluated
by a log-linear Poisson model. Age, period, and cohort factors were
included in the model. The likelihood ratio statistic and its degree
of freedom were derived from the differences in deviances and
in degrees of freedom, respectively, between the APC model and
each two-factor model. Parameters of the models were estimated
by means of the maximum likelihood method with SAS procedure
GENMOD (release SAS Enterprise Guide 4, SAS Institute Inc.).
3. Results
A total of 558,888 newly diagnosed cases of lung cancer were
reported between 1972 and 2007 in Canada, 363 903 (65%) in men
and 194,985 (35%) in women. Fig. 1 shows the temporal increase
in lung cancer incidence since 1972. The overall age-adjusted inci-
dence rate increased from 13.1 per 100,000 in 1972–1974 to 47.5
per 100,000 in 2005–2007 (APC: 3.9) in women; in the same time
period, the age-adjusted incidence rate increased slightly from 66.5
to 69.3 per 100,000 (APC: −0.1) in men. The age-adjusted incidence
rate reached its peak of 96.9 per 100,000 in 1984 and thereafter
rates began to fall. In 1972, the rate of incidence in men was approx-
imately 5 times that in women, whereas during the most recent
years this ratio fell to below 1.5.
Fig. 2A and B shows the temporal trends in histologi-
cal types of diagnosed lung cancer. Between1988–1990 and
2005–2007, male age-adjusted incidence rates of squamous cell
carcinoma decreased by 51% (from 28.4 to 13.9 per 100,000); of
18 X. Jiang et al. / Lung Cancer 78 (2012) 16–22

A 35

30

Incidence rate per 100 000 25

20

15

10

Time per iod (Years )

M-SQC M-ADC M-SCLC

B 18

16
Incidence rate per 100 000

14

12

10

Time period (Years)

F-SQC F-ADC F-SCLC

Fig. 2. (A) Age-adjusted incidence rate per 100,000 of squamous cell carcinoma, adenocarcinoma and small cell carcinoma of the lung in men, Canada, 1988–2007. (B)
Age-adjusted incidence rate per 100,000 of squamous cell carcinoma, adenocarcinoma and small cell carcinoma of the lung in women, Canada, 1988–2007.

adenocarcinoma decreased by 5% (from 18.7 to 17.8 per 100,000);
and of small cell carcinoma decreased by 41% (from 12.2 to 7.2
per 100,000). In comparison, in the same timeframe 1988–1990
to 2005–2007, female age-adjusted incidence rates of squamous
cell carcinoma decreased by 13% (from 6.4 to 5.6 per 100,000); of
adenocarcinoma increased by 51% (from 10.9 to 16.4 per 100,000);
and of small cell carcinoma decreased by 3% (from 5.8 to 5.6 per
100,000).
Table 1 shows the results of age-specific incidence rates by his-
tological type of lung cancer between 1988 and 2007. Women in
the 75–85+ year age group had the most rapid increase in incidence
of squamous cell carcinoma (APC: 1.6), adenocarcinoma (APC: 4.3),
and small cell carcinoma (APC: 2.2). Men aged 75–85+ years had
the highest increase of adenocarcinoma (APC: 1.1).
Tables 2A and 2B show the deviance of the age–period–cohort
model was smaller than that of both the age–period model and
of the age–cohort model, indicating a better fit of the data. Thus,
the full model was considered satisfactory for the time trends in
incidence of adenocarcinoma in men and in women (Table 2A);
all sex–curvature interactions with age, time period, and birth
cohort were statistically significant (P < 0.05), indicating that time
trends in men differ significantly from those of women in terms
of age at diagnosis, time period, and birth cohort curvature effects
(Table 2B).
The rates of squamous and small cell carcinoma have levelled
off during this study period. However, the rates of adenocarcinoma
have been increasing. Fig. 3 shows the different patterns of inci-
dence of adenocarcinoma for men and for women obtained from
fitting an age–period–cohort. These results suggest that the risk of
adenocarcinoma is decreasing in men and will be decreasing slowly
in women.
4. Discussion
The incidence of lung cancer in Canadian women increased sig-
nificantly, while in Canadian men, it increased until 1984, and
has since decreased to levels only slightly above those noted for
1972. The data shows that differing incidence patterns by tumour
 X. Jiang et al. / Lung Cancer 78 (2012) 16–22 19

Table 1
Age-specific incidence rate of histological sub-type of lung cancer and annual percent change (APC) in Canada, 1988–2007.

Age group (years) Histological sub-type Male Female

1988–1990 2005–2007 APC % (95% CI) 1988–1990 2005–2007 APC % (95% CI)

35–44 SQC 2.25 0.55 −7.95 (−9.37 to −6.51)** 1.15 0.34 −6.15 (−8.78 to −3.44)**
ADC 2.86 1.87 −3.05 (−4.66 to −1.42) 4.20 3.52 −1.12 (−2.66 to −0.44)
SCLC 1.31 0.49 −5.86 (−7.54 to −4.15) 1.13 0.53 −4.33 (−6.48 to −2.13)**

45–54 SQC 17.49 5.59 −6.60 (−7.11 to −6.08) 6.22 3.31 −4.02 (−5.11 to −2.92)**
ADC 18.53 12.63 −2.33 (−2.78 to −1.88) 17.73 21.34 0.59 (0.01 to 1.17)*
SCLC 12.44 4.60 −5.82 (−6.49 to −5.16)** 7.84 5.37 −2.45 (−2.98 to −1.91)

55–64 SQC 82.85 30.65 −5.78 (−6.09 to −5.47)** 20.70 14.45 −2.18 (2.72 to −1.65)**
ADC 61.32 46.19 −1.81 (−2.41 to −1.22) 38.66 52.23 1.57 (0.95 to 2.19)**
SCLC 40.23 19.75 −4.28 (−4.65 to −3.90)** 22.25 17.03 −1.87 (−2.50 to −1.24)*

65–74 SQC 172.32 84.99 −4.13 (−4.44 to −3.81)** 37.29 34.70 −0.58 (1.17 to 0.01)**
ADC 102.83 104.35 −0.26 (−0.77 to −0.25)** 49.69 86.63 3.05 (2.55 to 3.56)*
SCLC 69.11 43.72 −2.83 (−3.19 to −2.47)** 31.08 34.45 0.54 (0.04 to 1.03)**

75–85+ SQC 157.50 102.94 −2.64 (3.05 to −2.23)** 26.43 35.10 1.56 (1.02 to 2.10)**
ADC 85.51 104.94 1.07 (0.57 to 1.56)** 33.21 67.96 4.26 (3.78 to 4.74)**
SCLC 53.74 41.64 −1.51 (−1.84 to −1.18)** 16.54 23.19 2.23 (1.56 to 2.90)**

00–85+ SQC 28.41 13.87 −4.22 (−4.49 to −3.95)* 6.41 5.64 −0.90 (−1.31 to −0.48)**
ADC 18.74 17.75 −0.61 (−1.07 to −0.15)** 10.93 16.44 2.20 (1.70 to 2.61)**
SCLC 12.22 7.18 −3.22 (−3.46 to −2.98)* 5.84 5.55 −0.41 (−0.79 to −0.03)*

Abbreviations: ADC, Adenocarcinoma; APC, Annual Percent Change; P, linear statistical significance; SQC, squamous cell carcinoma; SCLC, small cell carcinoma.
Note: Rates were adjusted to the 1991 Canadian population. The APC were estimated by linear regression models of the logarithms of the age-standardized.
*
P < .05.
**
P < .01.

Table 2A
Comparison and evaluation of age–period–cohort modelling of Adenocarcinoma of the lung for ages 25–84 years, 1988–2007.

Terms in model Male Female

df Deviance a P-value b df Deviance a P-value b

Age 36 868.9 36 1314.1

Age–period 33 603.7 0.001 33 423.5 0.0001
Age–cohort 22 243.4 0.01 22 88.3 0.001
Age–period–cohort 20 239.1 20 35.8

Abbreviations: df, degrees of freedom; P-value representing statistical significance.

a
Deviance from the standard Poisson model.
b
P-values based on chi-square tests refer to comparison between two-factor model with the full age–period–cohort model.

histology and that the rates of squamous cell carcinoma and have increased substantially in women over the last three decades
small cell carcinoma have levelled off in men. The overall age- in Canada. Our analysis of the effects of age, period, and birth cohort
adjusted incidence rates of lung cancer for all histological types on time trends in lung cancer incidence suggests that birth cohort

2 Men

Women
1

0
Estimated Effects

-1

-2

-3

-4

-5

-6
1988
1993
1998
2003

1908
1913
1918
1923
1928
1933
1938
1943
1948
1953
1958
1963
1968
1973
1978
25
30
35
40
45
50
55
60
65
70
75
80

Age Period Cohort

Fig. 3. Age, period and cohort effects on incidence of adenocarcinoma of the lung in men (dashed line) and women (solid line) estimated by a three-factor model with
interaction terms for sex.
20 X. Jiang et al. / Lung Cancer 78 (2012) 16–22

Table 2B Statistics Canada [22]. Our analysis observed a downward trend

Significance tests for interaction between sex and curvature effects from
of daily smoking: the proportion of daily smokers was highest in
age–period–cohort modelling for incidence of adenocarcinoma of the lung,
1988–2007. women aged 20–34 years at 30.1% in 1994, and this decreased to
15.3% by 2009; in men, the proportion of daily smokers was highest
Source Likelihood ratio tests
in the 35–44-year age group at 32.8% in 1994, and this decreased to
df Adjusted deviance P 19.8% by 2009 (Fig. 4A and B). One study found that average daily
Age curvature 10 88.06 <0.001 cigarette consumption among smokers also decreased from 16.4 in
Period curvature 2 16.24 0.003 1999 to 13.6 in 2006 [23]. At equal levels of cigarette smoking expo-
Cohort curvature 13 61.61 <0.001 sure, women have higher risks of lung cancer than do men [24–28].
Our results show that adenocarcinoma was the most common his-
tological type of lung cancer in women, while in men squamous
effects have played a major role. Several factors may have affected cell carcinomas were the most common until about 1999, when
the observed trends for lung cancer and histological types. These adenocarcinomas became more common (Fig. 2A and B). It has
include (1) changes in the smoking rate in the population and the been suggested that switching from non-filter to filter cigarettes
type of cigarettes smoked; (2) changes in exposure to new environ- could explain why women have a sharper increase in lung cancer,
mental carcinogens; and (3) changes in the criteria and advanced especially of adenocarcinoma than do men [29]. Epidemiological
diagnosis technology for the histopathology diagnosis of lung can- studies have found that the use of filter cigarettes and of low-tar
cer. and low-nicotine cigarettes may be a risk factor for adenocarci-
Epidemiological studies suggest that cigarette smoking is asso- noma [5]. The tar and nicotine levels have fallen steadily for the
ciated with all major histological types of lung cancer [21]. Lung past 50 years from 38.4 mg in 1956 to 14 mg by 1980s [30], and
cancer rates have been decreasing in men since 1984, and this declined further to 0.85 mg of nicotine in 1990s [31]. Filter use could
change reflects changes in smoking patterns in Canada. Data on also result in taking larger puffs and keeping the smoke longer in
daily smoking since 1994 are available from the National Popula- the lungs to compensate for the lower yield of these cigarettes.
tion Health Survey and the Canadian Community Health Survey at This may cause an increase in the amount of smoke inhaled into

Fig. 4. (A) Prevalence of daily smoker by age group in Canada Females, 1994–2010. (B) Prevalence of daily smoker by age group in Canada Males, 1994–2010.
 X. Jiang et al. / Lung Cancer 78 (2012) 16–22
secondary and tertiary bronchi and consequently increased
deposits of smoke particles in the small airways [19]. Previous stud-
ies have also suggested that in the United States, the average nitrate
content of the blended cigarette tobacco increased gradually from
less than 0.5% in the 1950s to 1.2–1.5% in 1980s [32]. Increased
nitrate content is a factor for the increased formation of an organ-
specific carcinogen [32]. The agent has potentially contributed to
the risk of developing adenocarcinoma of the lung.
Previous studies suggested that long-term exposure to some
components of polluted air, especially nitrous oxides from the
emission of motor vehicles, may play a role in the increase of
lung cancer in developed countries [33,34]. Chen et al. [10] found
that motor vehicle density is associated with lung cancer: risks
for adenocarcinoma and squamous cell carcinoma are 136% and
68% higher for men living in areas with 937 motor vehicles per
square mile compared with those living in areas with about one
motor vehicle per square mile. Research has also shown that there
is increased incidence of adenocarcinoma in women in association
with exposure to indoor nitrous oxides is produced by fuel burn-
ing stoves, furnaces and fireplaces [35]. Recent Canadian studies
also suggested an increased risk of lung cancer in associated with
exposure to diesel emissions [36], particularly for squamous and
large cell carcinoma subtypes [37]. A 2004 Finnish study found that
exposure to motor vehicles (which use mainly gasoline) at young
ages was associated with an increasing risk of lung cancer only
in women [38]. Epidemiologic studies have reported that radon is
a human carcinogen and when it accumulates in closed spaces it
is a risk factor of lung cancer. Case-control studies have found an
increase in lung cancer risk of 10% per 100 Bq/m3 of measured radon
in North America and 8.4% per 100 Bq/m3 in radon levels in Europe
[39,40].
Advances in diagnostic technology may have had some effects
on the apparent increasing incidence of adenocarcinoma over the
study period. It is possible that some peripheral adenocarcinomas
invade and obliterate bronchi before diagnosis, leading to a mis-
diagnosis of bronchial carcinoma. Adenocarcinoma is not usually
bronchogenic but rather develops in the peripheral parenchyma of
the lung [19]. Changes in histological classification and improve-
ments in diagnostic techniques that increase access to the lung
periphery by, for example, using of the transthoracic aspiration
needle biopsy, may also increase number of adenocarcinoma cases
diagnosed [9,19].
Earlier research has found a positive BMI-lung cancer relation-
ship in never and former smokers [41,42]. This could be because
obese persons tend to have higher levels of estrogens, which are
converted from androgens in fat tissue [41]. High estrogen levels
may promote cancer cell growth [43]. Obese people have higher
circulating levels of insulin that also may act as a growth factor
on cancer cells [41]. The highest level of waist circumference has
been positively associated with risk of lung cancer for small cell
and squamous cell carcinoma of the lung [42]. It is likely, therefore,
that waist circumference is positively associated with these types
of lung cancer. An early detection artefact identified as a cohort
effect could reflect lifestyle factors or carcinogenic exposures dur-
ing early life and would affect the cohort throughout their whole
lifetime.
In conclusion, the underlying birth–cohort pattern observed
for lung cancer incidence in the Canadian population suggests
the effects of changes in smoking habits, cigarette design, and
manufacture and of changes in exposure to environmental car-
cinogens [19]. The observed results for adenocarcinoma incidence
trends are consistent with smoking trends over time, partic-
ularly differential patterns in smoking prevalence in men and
women. However, the relative risk with smoking is lower for ade-
nocarcinoma than with squamous cell carcinoma and small cell
carcinoma. This suggests that other exposures may play a role
21
in adenocarcinoma incidence, such as exposure to environmental
carcinogens.
Conflict of interest statement
The authors report no conflict of interest.
Acknowledgements
We would like to thank the following from which we obtained
data: the Canadian Cancer Registry, formerly the National Cancer
Incidence Reporting System. We gratefully acknowledge the coop-
eration of the provincial and territorial cancer registries that supply
the data to Statistics Canada. The authors also particularly thank Mr.
Robert Semenciw for his critical review of the manuscript.
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