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R E S E A R C H A R T I C L E Open Access
Risk of colorectal cancer among immigrants
to Ontario, Canada
Lawrence Paszat
1*
, Rinku Sutradhar
1
, Ying Liu
1
, Nancy N. Baxter
2
, Jill Tinmouth
3
and Linda Rabeneck
4
Abstract
Background: The risk of colorectal cancer (CRC) varies around the world and between females and males. We
aimed to compare the risk of CRC among immigrants to Ontario, Canada, to its general population.
Methods: We used an exposure-control matched design. We identified persons in the Immigration, Refugees and
Citizenship Canada Permanent Resident Database with first eligibility for the Ontario Health Insurance Plan between
July 1, 1991 and June 30, 2008 at age 40 years or older, and matched five controls by year of birth and sex on the
immigrant’s first eligibility date. We identified CRC from the Ontario Cancer Registry between the index date and
December 31, 2014. All analyses were stratified by sex. We calculated crude and relative rates of CRC. We estimated
risk of CRC over time by the Kaplan-Meier method and compared immigrants to controls in age and sex stratified
strata using log-rank tests. We modeled the hazard of CRC using Cox proportional hazards regression, accounting
for within-cluster correlation by a robust sandwich variance estimation approach, and assessed an interaction with
time since eligibility.
Results: Among females, 1877 cases of CRC were observed among 209,843 immigrants, and 16,517 cases among
1,049,215 controls; the crude relative rate among female immigrants was 0.623. Among males, 1956 cases of CRC
were observed among 191,792 immigrants and 18,329 cases among 958,960 controls; the crude relative rate
among male immigrants was 0.582.. Comparing immigrants to controls in all age and sex stratified strata, the log
rank test p< 0.0001 except for females aged > = 75 years at index, where p= 0.01. The age-adjusted hazard ratio
(HR) for CRC among female immigrants was 0.63 (95% CI 0.59, 0.67) during the first 10 years, and 0.66 (95% CI 0.59,
0.74) thereafter. Among male immigrants the age-adjusted HR = 0.55 (95% CI 0.52, 0.59) during the first 10 years
and increased to 0.63 (95% CI 0.57, 0.71) thereafter. The adjusted HR > = 1 only among immigrants born in Europe
and Central Asia.
Conclusions: The risk of CRC among immigrants to Ontario relative to controls varies by origin and over time since
immigration.
Keywords: Colorectal cancer, Cancer registry, Immigrants, Exposure-control matched design, Cox proprotional
hazards regression
Background
The incidence of CRC varies between males and females,
among individual nations and regions of the world, and
is associated with environmental, behavioural and gen-
etic factors [1–3]. Among nations with previously lower
incidence and current adoption of Western lifestyles, the
incidence is increasing [4–7], although India is a notable
example of an exception to this trend [8]. This trend has
also been described among immigrants to California
from previously lower incidence nations [9].
The incidence of CRC has been high in Canada com-
pared to most other countries. Crude and world age
standardized CRC incidence for Canada in 2012 are 68.5
and 35.2 per 100,000 respectively, compared to 50.7 and
27.0 per 100,000 respectively for Poland, 18.6 and 14.2
per 100,000 respectively for China, and 5.1 and 6.1 per
100,000 for India [10]. Lower risk of CRC among immi-
grants compared to non-immigrant populations with
* Correspondence: lawrence.paszat@ices.on.ca
1
University of Toronto, Institute for Clinical Evaluative Sciences, G106 2075
Bayview Avenue, Toronto, ON M4N3M5, Canada
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Paszat et al. BMC Gastroenterology (2017) 17:85
DOI 10.1186/s12876-017-0642-5
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Table 1 Description of immigrants and controls
Females Immigrants Controls
Overall count
Overall count 209,843 1,049,215
Year of index date
1991 - 1995 59,210 (28.2%) 290,050 (28.2%)
1996 - 2000 53,063 (25.3%) 265,315 (25.3%)
2001 - 2005 64,922 (30.9%) 324,610 (30.9%)
2006 - 2008 32,648 (15.6%) 163,240 (15.6%)
Person years by year of index date
1991 - 1995 940,939 person-years 5,292,802 person-years
1996 - 2000 725,818 person-years 3,915,579 person-years
2001 - 2005 646,525 person-years 3496,374 person-years
2006 - 2008 225,685 person-years 1,213,181 person-years
Followup time by year of index date
1991 - 1995
Mean (SD) 15.89 years (7.59) 17.88 years (6.03)
Median (IQR) 19.76 years (9.88 - 21.55) 20.28 years (16.26 - 21.78)
1996 - 2000
Mean (SD) 13.68 years (5.18) 14.76 years (4.12)
Median (IQR) 15.40 years (13.08 - 17.27) 15.76 years (14.31 - 17.44)
2001 - 2005
Mean (SD) 9.96 years (3.48) 10.77 years (2.62)
Median (IQR) 10.84 (9.24 - 12.43) 11.19 years (9.78 - 12.56)
2006 - 2008
Mean (SD) 6.91 years (2.09) 7.43 years (1.45)
Median (IQR) 7.44 years (6.71 - 8.27) 7.64 years (7.02 - 8.35)
Age at index date
40 - 49 years 97,829 (46.6%) 489,110 (46.6%)
50 - 59 years 51,806 (24.7%) 259,489 (24.7%)
60 - 69 years 41,029 (19.6%) 204,985 (19.5%)
70 - 74 years 10,342 (4.9%) 51,447 (4.9%)
> = 75 years 8837 (4.2%) 44,184 (4.2%)
Person years by age at index date
40 - 49 years 1,235,292 person-years 6,646,937 person-years
50 - 59 years 664,305 person-years 3,624,482 person-years
60 - 69 years 470,317 person-years 2,700,938 person-years
70 - 74 years 100,008 person-years 578,455 person-years
> = 75 years 69,043.82 person-years 367,123.65 person-years
Followup time by age at index date
40 - 49 years
Mean (SD) 12.63 years (5.78) 13.59 years (5.25)
Median (IQR) 12.34 years (8.44 - 17.27) 13.17 years (9.37 - 17.83)
50 - 59 years
Mean (SD) 12.82 years (6.24) 13.97 years (5.56)
Median (IQR) 12.63 years (8.25 - 18.24) 13.56 years (9.39 - 18.82)
Table 1 Description of immigrants and controls (Continued)
60 - 69 years
Mean (SD) 11.46 years (6.46) 13.18 years (5.70)
Median (IQR) 11.42 years (6.87 - 16.66) 12.90 years (8.72 - 17.86)
70 - 74 years
Mean (SD) 9.67 years (6.16) 11.24 years (5.53)
Median (IQR) 9.32 years (4.57 - 14.15) 10.98 years (7.30 - 15.17)
> = 75 years
Mean (SD) 7.81 years (5.28) 8.31 years (5.04)
Median (IQR) 7.34 years (3.39 - 11.48) 7.89 years (4.30 - 11.70)
Males Immigrants Controls
Overall count 191,792 958,960
Year of index date
1991 - 1995 48,793 (25.4%) 243,965 (25.4%)
1996 - 2000 51,328 (26.8%) 256,640 (26.8%)
2001 - 2005 62,371 (32.5%) 311,855 (32.5%)
2006 - 2008 29,300 (15.3%) 146,500 (15.3%)
Person years by year of index date
1991 - 1995 744,331 person-years 4,121,283 person-years
1996 - 2000 685,887 person-years 3,702,915 person-years
2001 - 2005 601,385 person-years 3,273,836 person-years
2006 - 2008 196,843 person-years 1,062,171 person-years
Followup time by year of index date
1991 - 1995
Mean (SD) 15.25 years (7.73) 16.89 (6.58)
Median (IQR) 19.45 years (8.28 - 21.30) 19.78 (13.12 - 21.56)
1996 - 2000
Mean (SD) 13.36 years (5.32) 14.43 (4.34)
Median (IQR) 15.22 years (11.58 - 17.15) 15.56 (14.16 - 17.32)
2001 - 2005
Mean (SD) 9.64 years (3.69) 10.50 (2.88)
Median (IQR) 10.62 years (9.03 - 12.36) 11.04 (9.50 - 12.50)
2006 - 2008
Mean (SD) 6.72 years (2.26) 7.25 (1.66)
Median (IQR) 7.37 years (6.58 - 8.24) 7.56 (6.90 - 8.31)
Age at index date
40 - 49 years 106,112 (55.3%) 530,757 (55.3%)
50 - 59 years 40,062 (20.9%) 200,563 (20.9%)
60 - 69 years 31,575 (16.5%) 157,362 (16.4%)
70 - 74 years 8070 (4.2%) 40,492 (4.2%)
> = 75 years 5973 (3.1%) 29,786 (3.1%)
Person years by age at index date
40 - 49 years 1,289,734 person-years 7,047,301 person-years
50 - 59 years 485,469 person-years 2,620,618 person-years
60 - 69 years 344,004 person-years 1,886,805 person-years
70 - 74 years 69,618 person-years 390,565 person-years
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 2 of 11
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high prevalence of CRC has been described in Canada
[11, 12], the USA [13], and the UK [14].
We aimed to compare the risk of CRC among immi-
grants to Ontario, Canada, to its general population, and
to examine if the risk changed over time since arrival,
stratified by world region of birth and country of birth
of immigrants. Ontario recently established a CRC
screening program, ColonCancerCheck (CCC), [15],
consisting of biennial guaiac fecal occult blood testing
(gFOBT) for persons 50 - 74 without a first degree rela-
tive affected by CRC (approximately 89% of the popula-
tion of Ontario), and screening colonoscopy for those
with an affected first degree relative (approximately 11%
of the population of Ontario) [16, 17]. CCC sends letters
to all 50–74 year old residents of Ontario inviting them
to discuss CRC screening with their primary care pro-
viders, who are supplied with gFOBT sampling kits to
distribute to their eligible patients. It is already known
that immigrants to Ontario are less likely to participate
in colorectal screening than non-immigrants [18], as is
true elsewhere in North America and Europe [19–22].
The goal of this work is to inform CCC of the risk of
CRC stratified by origin of immigrants and time since
immigration, so that its efforts to improve screening par-
ticipation among immigrants may be tailored by this
information.
Methods
This work was approved by the Research Ethics Board of
Sunnybrook Health Sciences Centre and conducted at
the Institute for Clinical Evaluative Sciences (ICES). We
used three population-wide databases, in which each
observation is identified by an encryption of the unique
Ontario Health Insurance Number and are thereby link-
able deterministically. The Immigration, Refugees and
Citizenship Canada Permanent Resident Database
(IRCC) contains the date of arrival in Canada, the
intended province of residence in Canada, and the coun-
try of birth; permission to access the data was granted
by the Government of Canada. The Registered Persons
Database (RPDB) contains the age, sex, dates of eligiblity
for the universal, single-payer Ontario Health Insurance
Plan (OHIP), date of last contact with health care ser-
vices in Ontario, and status on the date of last contact
for each OHIP beneficiary; permission to access the data
was granted by the Ministry of Health and Long Term
Care of Ontario. The Ontario Cancer Registry (OCR)
contains the diagnosis code for invasive cancer (Inter-
national Classification of Diseases version 10) and its
date of diagnosis, for all residents of Ontario diagnosed
with a malignancy; permission to access the data was
granted by Cancer Care Ontario.
We used an exposure-control matched design. We
identified persons from the IRCC with arrival in Ontario,
and whose first eligibility for OHIP fell between July 1,
1991 and June 30, 2008 at age 40 years or older, in the
Registered Persons Database (RPDB). The first eligibility
date was labeled the index date for each immigrant.
From the IRCC, we extracted ‘country of birth’for each
immigrant, and categorized ‘country of birth’into a
modified classification of selected world regions (East
Asia and Pacific; Europe and Central Asia; Latin Amer-
ica and Caribbean, Middle East and North Africa, South
Asia, Sub-saharan Africa) [23–25]. We matched 5 con-
trols from the RPDB alive on the corresponding immi-
grant’s index date and not found in the IRCC database
between 1986 to 2010, on year of birth and sex.
We identified CRC (diagnosis codes C180, C182 -
C189, C19, C20) from the OCR among immigrants and
controls between the index date and December 31, 2014.
All immigrants and controls were followed to date of
last contact, date of CRC diagnosis, or December 31,
2014, whichever came first.
We examined the distributions of various characteris-
tics between immigrants and controls in the matched
cohort. All analyses were stratified by sex. The crude
rates of CRC (per 100,000 person-years) among immi-
grants and controls, along with the corresponding crude
relative rate of CRC, were calculated.
To examine the association between immigration
status and the hazard of CRC, the outcome was de-
fined as the time to diagnosis of CRC (from the index
date). Individuals were censored at the time of study
end or death, whichever occurred first. Kaplan Meier
methods were used to graphically examine the risk of
CRC over time among immigrants compared to
Table 1 Description of immigrants and controls (Continued)
> = 75 years 39,621 person-years 214,918 person-years
Followup time by age at index date
40 - 49 years
Mean (SD) 12.15 years (5.85) 13.28 years (5.23)
Median (IQR) 12.12 years (8.09 - 16.70) 13.09 years (9.31 - 17.36)
50 - 59 years
Mean (SD) 12.12 years (6.11) 13.07 years (5.57)
Median (IQR) 11.90 years (7.75 - 17.18) 12.61 years (8.69 - 17.70)
60 - 69 years
Mean (SD) 10.89 years (6.39) 11.99 years (5.77)
Median (IQR) 10.81 years (6.36 - 15.76) 11.65 years (7.81 - 16.43)
70 - 74 years
Mean (SD) 8.63 years (5.80) 9.65 years (5.29)
Median (IQR) 8.16 years (3.81 - 12.62) 9.11 years (6.09 - 13.08)
> = 75 years
Mean (SD) 6.63 years (5.03) 7.22 years (4.66)
Median (IQR) 6.18 years (2.18 - 9.90) 6.90 years (3.39 - 10.31)
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 3 of 11
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Table 2 Crude rates of CRC among immigrants and controls and crude relative rate among immigrants
Females Immigrants CRC among
immigrants
Controls CRC among
controls
Crude rate among
immigrants
a
Crude rate
among
controls
a
Crude relative
rate among
immigrants
a
Overall 209,843 1877 1,049,215 16,517 0.203 0.325 0.623
Age at index date
40 - 49 years 97,829 (46.6%) 442 (23.5%) 489,110 (46.6%) 3180 (19.3%) 0.098 0.131 0.748
50 - 59 years 51,806 (24.7%) 428 (22.8%) 259,489 (24.7%) 4299 (26.0%) 0.177 0.325 0.543
60 - 69 years 41,029 (19.6%) 606 (32.3%) 204,985 (19.5%) 6027 (36.5%) 0.353 0.611 0.577
70 - 74 years 10,342 (4.9%) 200 (10.7%) 51,447 (4.9%) 1720 (10.4%) 0.548 0.815 0.673
> = 75 years 8837 (4.2%) 201 (10.7%) 44,184 (4.2%) 1291 (7.8%) 0.798 0.963 0.828
Selected world regions
of birth
205,469 1854 1,027,345 16,217
East Asia and Pacific 67,385 (32.8%) 748 (40.4%) 336,925 (32.8%) 5771 (35.6%) 0.253 0.345 0.731
Europe and Central
Asia
38,315 (18.7%) 599 (32.3%) 191,575 (18.7%) 3107 (19.2%) 0.340 0.331 1.027
Latin America and
the Caribbean
23,210 (11.3%) 191 (10.3%) 116,050 (11.3%) 1789 (11.0%) 0.176 0.310 0.569
Middle East and
North Africa
16,222 (7.9%) 106 (5.7%) 81,110 (7.9%) 1114 (6.9%) 0.155 0.298 0.519
South Asia 52,103 (25.4%) 162 (8.7%) 260,515 (25.4%) 3764 (23.2%) 0.072 0.308 0.233
Sub-saharan Africa 8234 (4.0%) 48 (0.3%) 41,170 (4.0%) 672 (4.1%) 0.134 0.344 0.389
Selected nations of
birth
146,545 1230 732,725 11,565
India 29,744 (20.3%) 73 (5.9%) 148,720 (20.3%) 2173 (18.8%) 0.059 0.315 0.187
Pakistan 7907 (5.4%) 18 (1.5%) 39,535 (5.4%) 435 (3.8%) 0.056 0.247 0.226
Sri Lanka 10,256 (7.0%) 48 (3.9%) 51,280 (7.0%) 893 (7.7%) 0.093 0.343 0.270
China / Hong Kong /
Taiwan
39,886 (27.2%) 535 (43.5%) 199,430 (27.2%) 3679 (31.8%) 0.308 0.364 0.845
Philippines 16,461 (11.2%) 125 (7.6%) 82,305 (11.2%) 1232 (10.7%) 0.171 0.316 0.542
Korea 4194 (2.9%) 25 (2.0%) 20,970 (2.9%) 239 (2.1%) 0.145 0.249 0.585
Iran 6754 (4.6%) 40 (3.3%) 33,770 (4.6%) 443 (3.8%) 0.139 0.287 0.484
Poland 5373 (3.7%) 83 (6.8%) 26,865 (3.7%) 544 (4.7%) 0.287 0.351 0.818
Guyana 5072 (3.5%) 30 (2.4%) 25,360 (3.5%) 447 (3.9%) 0.116 0.333 0.349
Jamaica 5012 (3.4%) 65 (5.3%) 25,060 (3.4%) 427 (3.7%) 0.260 0.332 0.783
United States of
America
3906 (2.7%) 18 (1.5%) 19,530 (2.7%) 258 (2.2%) 0.127 0.279 0.454
Russia 4686 (3.2%) 70 (5.7%) 23,430 (3.2%) 288 (2.5%) 0.352 0.283 1.244
United Kingdom 3734 (2.6%) 43 (3.5%) 18,670 (2.6%) 299 (2.6%) 0.292 0.356 0.819
Ukraine 3560 (2.4%) 57 (4.6%) 17,800 (2.4%) 208 (1.8%) 0.367 0.264 1.389
Males
Overall 191,792 1956 958,960 18,329 0.240 0.413 0.582
Age at index date
40 - 49 years 106,112 (55.3%) 580 (29.7%) 530,757 (55.3%) 4758 (26.0%) 0.123 0.185 0.666
50 - 59 years 40,062 (20.9%) 476 (24.3%) 200,563 (20.9%) 4671 (25.5%) 0.269 0.488 0.550
60 - 69 years 31,575 (16.5%) 610 (31.2%) 157,362 (16.4%) 6237 (34.0%) 0.486 0.906 0.536
70 - 74 years 8070 (4.2%) 168 (8.6%) 40,492 (4.2%) 1676 (9.1%) 0.661 1.176 0.562
> = 75 years 5973 (3.1%) 122 (6.2%) 29,786 (3.1%) 987 (5.4%) 0.844 1.258 0.670
Selected world regions
of birth
187,835 1923 939,175 17,999
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 4 of 11
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controls, and log-log plots were used to assess if the
hazard functions were proportional. Multivariable
extended Cox regression models were then imple-
mented, controlling for baseline characteristics [26].
Note that since we performed exposure-control
matching, as opposed to case-control matching, the
matched characteristics are permitted in the multivar-
iable model. To account for within-cluster correlation
that may arise due to the matched design, a robust sand-
wich variance estimation approach was used. As it was
possible for the association between immigration status
and hazard of CRC to change over time, we included an
interaction between immigration status (immigrant or
non-immigrant) and time, where time was categorized
into two intervals using the point of 10 years after index
[27]. Analyses were conducted with SAS version 9.3 (SAS
Institute, Inc., Cary, NC). All statistical tests were two
sided, and Pvalues less than .05 were considered statisti-
cally significant.
Results
We identified 209,843 female immigrants with 2,538,966
person-years of follow-up to death, diagnosis of CRC, or
December 31, 2014, whichever came first. The index
date for 84.4% of female immigrants fell between July 1,
1991 and December 31, 2005 (i.e. between 9 and 23 years
prior to the last available date for records of CRC diag-
nosis). We matched them to 1,049,215 controls with
13,917,936 person-years of follow-up. We identified
191,792 male immigrants (for whom the index date fell
between July 1, 1991 and December 31, 2005 among
84.7%) with 2,228,448 person-years of follow-up and
matched them to 958,960 controls with 12,160,208
person-years of follow-up (Table 1). Mean and median
duration follow-up of followup are modestly longer for
controls compared to immigrants; this is due to higher
emigration from Ontario among immigrants compared
to controls, rather than higher mortality. The crude rela-
tive death rate among immigrants compared to controls
is 0.555 per 100,000 person-years, and is lower among
all strata of age at index and among all world regions
and countries of birth of immigrants (data not shown).
Among female immigrants, 58.2% had been born in the
East Asia and Pacific or the South Asia world regions, and
146,545 / 209,843 (69.8%) had been born in one of 14
among all 211 represented countries of birth, with 27.2%
Table 2 Crude rates of CRC among immigrants and controls and crude relative rate among immigrants (Continued)
East Asia and Pacific 56,546 (30.1%) 787 (40.9%) 282,730 (30.1%) 6209 (34.5%) 0.330 0.464 0.711
Europe and Central
Asia
32,489 (17.3%) 570 (29.6%) 162,445 (17.3%) 2968 (16.5%) 0.386 0.377 1.024
Latin America and
the Caribbean
17,474 (9.3%) 136 (7.1%) 87,370 (9.3%) 1591 (8.8%) 0.174 0.385 0.452
Middle East and
North Africa
18,355 (9.8%) 164 (8.5%) 91,775 (9.8%) 1589 (8.8%) 0.221 0.389 0.570
South Asia 54,756 (29.2%) 205 (10.7%) 273,780 (29.2%) 5025 (27.9%) 0.090 0.413 0.218
Sub-saharan Africa 8215 (4.4%) 61 (3.2%) 41,075 (4.4%) 617 (3.4%) 0.180 0.329 0.545
Selected nations of birth 133,234 1341 666,170 13,209
India 30,557 (22.9%) 98 (7.3%) 152,785 (22.9%) 3028 (22.9%) 0.079 0.450 0.177
Pakistan 10,875 (8.2%) 34 (2.5%) 54,375 (8.2%) 697 (5.3%) 0.078 0.291 0.268
Sri Lanka 8005 (6.0%) 58 (4.3%) 40,025 (6.0%) 930 (7.0%) 0.150 0.489 0.307
China / Hong Kong / Taiwan 35,957 (27.0%) 562 (41.9%) 179,785 (27.0%) 4246 (32.1%) 0.376 0.495 0.759
Philippines 11,588 (8.7%) 115 (8.6%) 57,940 (8.7%) 1152 (8.7%) 0.229 0.433 0.528
Korea 4257 (3.2%) 41 (3.1%) 21,285 (3.2%) 252 (1.9%) 0.234 0.255 0.920
Iran 7381 (5.5%) 86 (6.4%) 36,905 (5.5%) 636 (4.8%) 0.279 0.385 0.724
Poland 3343 (2.5%) 70 (5.2%) 16,715 (2.5%) 373 (2.8%) 0.383 0.377 1.017
Guyana 3601 (2.7%) 31 (2.3%) 18,005 (2.7%) 427 (3.2%) 0.176 0.471 0.374
Jamaica 3496 (2.6%) 31 (2.3%) 17,480 (2.6%) 335 (2.5%) 0.184 0.394 0.466
United States of
America
3506 (2.6%) 28 (2.1%) 17,530 (2.6%) 289 (2.2%) 0.230 0.372 0.618
Russia 3662 (2.8%) 71 (5.3%) 18,310 (2.8%) 256 (1.9%) 0.463 0.316 1.464
United Kingdom 4142 (3.1%) 62 (4.6%) 20,710 (3.1%) 370 (2.8%) 0.373 0.405 0.921
Ukraine 2864 (2.1%) 54 (4.0%) 14,320 (2.1%) 218 (1.7%) 0.437 0.344 1.269
a
per 100,000 person-years
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having been born in China / Hong Kong / Taiwan and
20.3% in India. Among male immigrants, 59.3% had been
born in the East Asia and Pacific or South Asia world re-
gions, and133,234 / 191,792 (69.5%) had been born in one
of 14 among all 213 represented countries of birth, with
27.0% having been born in China / Hong Kong / Taiwan
and 22.9% in India (Table 2). Among females, 1877 cases
of CRC were observed among immigrants and 16,517
among controls; the crude rate of CRC among female im-
migrants was 0.203 per 100,000 person-years, compared
to 0.325 per 100,000 person-years among female controls,
increased by age at index date, and varied by world region
and by country of birth Overall, the crude relative rate of
CRC among female immigrants was 0.623, ranging from
0.233 among those born in South Asia to 1.027 among
those born in Europe and Central Asia. The crude relative
rate exceeded 1.000 for those born in Russia and Ukraine.
Among males, 1956 cases of CRC were observed among
immigrants and 18,329 among controls; the crude rate
among immigrants was 0.24 per 100,000 person-
years, compared to 0.413 among controls, increased
by age at index date, and varied by world region and
country of birth. Compared to male controls, the
overall crude relative event rate among male immi-
grants was 0.582. Among world regions, the crude
relative rates of CRC for immigrants ranged from
0.218 for those born in South Asia to 1.024 for
Europe and Central Asia. The crude relative rate of
CRC exceeded 1.000 for those born in Poland,
Russia, and Ukraine (Table 2).
By the Kaplan-Meier method, the risk of colorectal
cancer diagnosis over time was consistently higher
among female controls compared to immigrants in all
age strata (log rank test p< 0.0001 except for females
Fig. 1 Forest plot for Adjusted Hazard Ratio for CRC among females by birth country
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 6 of 11
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> = 75 years of age, log rank test p= 0.01), and among
male controls compared to immigrants (log rank test
p< 0.0001 in all age strata). Examination of sex and age
stratified log-log plots of time to colorectal cancer dem-
onstrated that the hazards of CRC were proportional in
all sex and age strata. (not shown).
The age-adjusted hazard ratio (HR) for CRC among fe-
male immigrants was 0.63 (95% CI 0.59, 0.67) during the
first 10 years after arrival, and 0.66 (95% CI 0.59, 0.74)
thereafter. Among male immigrants the age-adjusted
HR = 0.55 (95% CI 0.52, 0.59) during the first 10 years,
and 0.63 (95% CI 0.57, 0.71) thereafter.
The age-adjusted HRs vary among the world regions,
and in general are significantly less than 1.00 except
among those born in Europe and Central Asia. The
point estimates of the age-adjusted HRs > 10 years after
the index date are increased compared to <= 10 years
for some regions and the respective 95% confidence in-
tervals include unity. Figures 1 and 2 display forest plots
of the stratified age-adjusted HRs for CRC for the 14
countries of birth with the largest number of immi-
grants, for females and males respectively. There are
greater differences in age-adjusted HRs among these 14
countries of birth compared to those among the seven
world regions of birth in Table 3.
Discussion
The risk of CRC among immigrants who arrived in On-
tario at the age of 40 years or older, between 1991 and
2008, is lower overall compared to age-matched controls
for more than 10 years after immigration. Their risk varies
among world regions of birth, and among the 14 countries
in which the majority of immigrants were born. All arrived
in Ontario prior to the inception of the CCC screening
Fig. 2 Forest plot for Adjusted Hazard Ratio for CRC among males by birth country
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 7 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Table 3 Adjusted cox models of CRC risk stratified by sex
Variable Females Males
Univariate HR
(95% CI)
Multivariate HR
(95% CI)
Multivariate HR
(95% CI) with
interaction
Univariate HR
(95% CI)
Multivariate HR
(95% CI)
Multivariate HR
(95% CI) with
interaction
Overall
Immigrant 0.63 (0.60, 0.66) 0.64 (0.61, 0.67) 0.59 (0.56, 0.62) 0.59 (0.56, 0.62)
Nonimmigrant controls Reference Reference Reference Reference
Age at index
40 - 49 Reference Reference Reference Reference Reference Reference
50 - 59 2.35 (2.25, 2.45) 2.35 (2.25, 2.45) 2.35 (2.25, 2.45) 2.59 (2.50, 2.70) 2.60 (2.50, 2.70) 2.60 (2.50, 2.70)
60 - 69 4.54 (4.36, 4.73) 4.53 (4.35, 4.72) 4.53 (4.35, 4.72) 4.94 (4.77, 5.12) 4.94 (4.77, 5.12) 4.94 (4.77, 5.12)
70 - 74 6.54 (6.19, 6.91) 6.52 (6.17, 6.88) 6.52 (6.17, 6.88) 6.99 (6.62, 7.37) 6.98 (6.62, 7.37) 6.98 (6.62, 7.37)
> = 75 8.63 (8.11, 9.17) 8.63 (8.12, 9,17) 8.63 (8.12, 9.17) 8.46 (7.93, 9.03) 8.47 (7.94, 9.04) 8.47 (7.94, 9.04)
Immigrant < = 10 years
since index date
0.62 (0.58, 0.66) 0.63 (0.59, 0.67) 0.55 (0.52, 0.59) 0.55 (0.52, 0.59)
Controls <= 10 years since
index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.65 (0.58, 0.73) 0.66 (0.59, 0.74) 0.64 (0.57, 0.72) 0.63 (0.57, 0.71)
Controls <= 10 years since
index date
Reference Reference Reference Reference
Age adjusted models for
world region of birth
East Asia and Pacific
Immigrant < = 10
years since index date
0.70 (0.63, 0.78) 0.72 (0.65, 0.80) 0.70 (0.64, 0.78) 0.72 (0.65, 0.79)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10
years since index date
0.79 (0.66, 0.95) 0.80 (0.67, 0.96) 0.74 (0.62, 0.89) 0.73 (0.61, 0.87)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Europe and Central Asia
Immigrant< = 10
years since index date
1.10 (0.98, 1.23) 1.09 (0.97, 1.22) 1.02 (0.90, 1.15) 1.01 (0.90, 1.14)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.96 (0.77, 1.18) 0.96 (0.78, 1.19) 1.05 (0.85, 1.30) 1.04 (0.84, 1.29)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Latin America and the
Caribbean
Immigrant < = 10
years since index date
0.58 (0.47, 0.71) 0.59 (0.48, 0.72) 0.45 (0.35, 0.57) 0.46 (0.36, 0.58)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.56 (0.39, 0.81) 0.58 (0.41, 0.84) 0.46 (0.30, 0.71) 0.46 (0.30, 0.71)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Middle East and North
Africa
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 8 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
program and many of those diagnosed with CRC received
the diagnosis prior to its inception. It is already known
that immigrants to Ontario are less likely to participate in
CRC screening [18]. In its future efforts to improve par-
ticipation in CRC screening by immigrants, CCC should
include tailored approaches to the sizable numbers of im-
migrants from countries of birth for which the age-
adjusted risks of CRC are close to, or equivalent to, those
of the non-immigrant controls.
This is an important study comprising a large popula-
tion of 401,635 immigrants from 213 countries. The
available data elements are appropriate for a time-to-
event analytic approach, that is more powerful and illu-
minating than crude rates and incidence ratios, and it
was possible to examine the potential interaction be-
tween status as an immigrant and time since immigra-
tion. Prior studies of the risk of CRC among immigrants
have substantial weaknesses compared to this work. A
national study among immigrants to Canada from 1980
to 1990, using probabilistic rather than deterministic
linkage, with followup for CRC among other cancer
types to 1998, had fewer immigrants despite being
nation-wide, 90.8% of whom were <= 44 years of age at
the time of immigration [11]. The young age distribution
is reflected in the low number of cases of CRC observed
among immigrants (n= 71 compared to n= 3833); the
low number of cases prevented the use of time to event
analytic methods and stratification by country of birth.
Other Canadian studies of small numbers of immigrants
were unable to use to time to event methods and did
not examine the worldwide distribution of origin of im-
migrants [12, 28]. Studies from the US [13] and the UK
[14] examined relative rates between immigrants from a
limited number of origins.
A limitation of the study is the inability to match im-
migrants to controls on comorbidity or past medical his-
tory on the matching date. Although immigrants and
controls hypothetically could be linked to census-level
ecologic measures of socio-economic status by postal
code on the matching date, we doubt that those mea-
sures at the time of the arrival of immigrants in Ontario
would be valid descriptors of socio-economic influences
on the health of the immigrants up to the time of their
arrival. A further limitation is the lack of data about the
risks of CRC beyond two decades since arrival, which
might plausbility increase as observed among certain
ethnic groups in California [9]. We are unable to com-
ment on the association of colorectal screening with im-
migration status, or the association between colorectal
screening among immigrants and their risk of colorectal
Table 3 Adjusted cox models of CRC risk stratified by sex (Continued)
Immigrant< = 10
years since index date
0.52 (0.40, 0.67) 0.52 (0.40, 0.68) 0.49 (0.39, 0.61) 0.48 (0.38, 0.60)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.54 (0.33, 0.87) 0.54 (0.34, 0.88) 0.72 (0.49, 1.07) 0.70 (0.47, 1.03)
Controls <= 10 years
since index date
Reference Reference Reference Reference
South Asia
Immigrant < = 10
years since index date
0.23 (0.19, 0.28) 0.24 (0.19, 0.29) 0.17 (0.14, 0.21) 0.18 (0.14, 0.22)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.24 (0.17, 0.35) 0.25 (0.17, 0.37) 0.28 (0.20, 0.40) 0.28 (0.20, 0.40)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Sub-saharan Africa
Immigrant < = 10
years since index date
0.27 (0.17, 0.43) 0.27 (0.17, 0.43) 0.39 (0.26, 0.59) 0.38 (0.25, 0.57)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Immigrant > 10 years
since index date
0.56 (0.26, 1.18) 0.56 (0.26, 1.18) 0.78 (0.40, 1.53) 0.75 (0.38, 1.48)
Controls <= 10 years
since index date
Reference Reference Reference Reference
Paszat et al. BMC Gastroenterology (2017) 17:85 Page 9 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
cancer in this study, because the population-based CRC
screening programme in Ontario was introduced near
the end of the observation period.
The variability of the risk of CRC among immigrants
to Ontario relative to controls, by region or country of
origin, has implications for colorectal screening in On-
tario. Efforts to improve screening participation among
immigrants may be tailored by this information. Further-
more, the risk of CRC should be monitored during the
period beyond two decades since arrival.
Conclusions
The risk of CRC among immigrants to Ontario varies by
length of time residing in Ontario and birthplace, and,
with the exception of those born in the Europe andCen-
tral Asia region, and in the individual countries of Russia
and Ukraine, is lower than that for non-immigrants for
up to two decades after arrival.
Abbreviations
CCC: Colon Cancer Check; CI: Confidence interval; CRC: Colorectal cancer;
HR: Hazard ratio; ICES: Institute for Clinical Evaluative Sciences;
IRCC: Immigration, Refugees and Citizenship Canada; OCR: Ontario Cancer
Registry; OHIP: Ontario Health Insurance Plan
Acknowledgements
This study is based on data and information from the Government of
Canada (Immigration, Refugees and Citizenship Canada (IRCC)'s Permanent
Resident Database), the Ministry of Health and Long Term Care of Ontario
(RPDB and OHIP), and Cancer Care Ontario (OCR). The opinions, results, view,
and conclusions reported in this paper are those of the authors and do not
necessarily reflect those of the Government of Canada, the Ministry of Health
and Long Term Care of Ontario or Cancer Care Ontario. No endorsement by
the Government of Canada, the Ministry of Health and Long Term Care of
Ontario, or Cancer Care Ontario is intended or should be inferred.
Funding
This work was funded by an Applied Cancer Research Unit grant from
Cancer Care Ontario to Lawrence Paszat. Cancer Care Ontario had no role in
the design of the study and collection, analysis, and interpretation of data
and in writing the manuscript. This study was supported by the Institute for
Clinical Evaluative Sciences (ICES), which is funded by an annual grant from
the Ontario Ministry of Health and Long-Term Care (MOHLTC).
Availability of data and materials
The data set from this study is held securely in coded form at the Institute for
Clinical Evaluative Sciences (ICES). While data sharing agreements prohibit ICES
from making the data set publicly available, access may be granted to those
who meet pre-specified criteria for confidential access (www.ices.on.ca/DAS).
The full data set creation plan is available from the authors upon request. The
data that support the findings of this study are available from the Government
of Canada (Immigration, Refugees and Citizenship Canada Permanent Resident
Database), the Ontario Ministry of Health and Long Term Care (Ontario Health
Insurance Plan and Registered Person’s Database), and Cancer Care Ontario
(Ontario Cancer Registry) but restrictions apply to the availability of these data,
which were used under license for the current study, and so are not publicly
available. Data are however available from the Government of Canada, the
Ontario Ministry of Health and Long Term Care, and Cancer Care Ontario
respectively, to qualified and approved investigators.
Authors’contributions
This research was designed by LP, RS, NB, JT and LR. The data were extracted
and analyzed by YL under the supervision of LP and RS. The data were
interpreted by LP, RS, NB, JT and LR. The manuscript was drafted by LP. All
authors read and approved the final manuscript.
Ethics approval and consent to participate
This research was approved by the Research Ethics Board of Sunnybrook
Health Sciences Centre. All data had been previously stripped of personal
identifiers so that consent to participate was not required.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional affiliations.
Author details
1
University of Toronto, Institute for Clinical Evaluative Sciences, G106 2075
Bayview Avenue, Toronto, ON M4N3M5, Canada.
2
University of Toronto, St
Michael’s Hospital, 30 Bond Street, Toronto, ON M5B1W8, Canada.
3
University
of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue,
Toronto, ON M4N3M5, Canada.
4
University of Toronto, Prevention and
Cancer Control, Cancer Care Ontario, 620 University Avenue, Toronto, ON
M4, Canada.
Received: 3 March 2017 Accepted: 29 June 2017
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