A systematic review of the articles regarding the benefit of colorectal cancer genetic testing

1. BENEFIT OF COLORECTAL
CANCER GENETIC TESTING: A
SYSTEMATIC REVIEW
Abdul Rahman Ramdzan1, Faizal Madrim1, Rizal Abdul Manaf1
1 Community Health Department, National University of Malaysia
1

2. CONTENTS
• Abstract
• Introduction
• Methods
• Results
• Discussions and Conclusion
2

3. ABSTRACT
Objectives: To conduct a systematic review of the benefit of genetic testing for colorectal cancer
Data sources: PUBMED and Scopus were searched for the period 2012- 2017.
Study selection: Studies were eligible if published in a peer-reviewed journal in English, included adult with a family history
of colorectal cancer who underwent genetic testing and had either a randomised controlled trial or prospective design
Data synthesis: As there was considerable heterogeneity in populations and measures, results were summarised rather than
subjected to meta-analysis.
Results: Overall, genetic testing appear to produce benefits and effective in colorectal cancer detection. Genetic testing will
inform patient or family members have an increased risk of developing a condition later in life. The results can provide a
sense of relief from uncertainty and help people make informed decisions about managing their health care.
Conclusions: To date, the data on benefit & effectiveness after genetic testing are reassuring. Although benefits of
screening are likely to outweigh harms for populations at high risk of colorectal cancer, more information is needed about
the harmful effects of screening, the community's responses to screening and costs of screening for different healthcare
systems before widespread screening can be recommended.
Keywords: Colorectal cancer, Genetic testing, Benefit, Effectiveness
3

4. CANCER IN MALAYSIA
• A total of 103,507 new cancer cases were diagnosed in
Malaysia for the period of 2007- 2011.
45%
55%
Lifetime risk
Male : 1 in 10/10%
Lifetime risk
Female: 1 in 9/ 11%
National Cancer Registry, 2007-2011
4

5. 10 MOST COMMON CANCERS
National Cancer Registry, 2007-2011
5

6. TEN COMMON CANCERS
BY GENDER
National Cancer Registry, 2007-2011
3.4%/ 1 in
30
1.8% / 1 in 56
1.3% / 1 in 741.8% / 1 in 55
0.7% / 1 in 135
Lifetime risk :the likelihood that a person who is free of
a certain type of cancer will develop or die from that
type of cancer during his or her lifetime.
0.9% / 1 in 116
0.6% / 1 in 158
0.9% / 1 in 117
6

7. COLORECTAL CANCER
• 13,693 cases of colorectal cancer in Malaysia from 2007-
2011 (2738.6 per year)
• Male : Lifetime risk is ~1.8% (1 in 56)
- Chinese : 2.6% (1 in 39)
- Malay : 1.4% (1 in 72)
- Indian : 1.2% (1 in 82)
• Female : Lifetime risk is ~1.4% (1 in 74)
- Chinese : 2% (1 in 34)
- Indian : 1.1% (1 in 91)
- Malay : 1% (1 in 100)
National Cancer Registry, 2007-2011
8

8. COLORECTAL CANCER IN
MALAYSIA
National Cancer Registry, 2007-2011
9

9. INTERNATIONAL COMPARISONS
10

10. GENETIC
TESTING
Besides genetic testing, colonoscopy, flexible
sigmoidoscopy, stool-based screening (FOBT,
FIT), CT colonography
Genetic mutations can
have harmful, beneficial,
neutral or uncertain effects
on health.
Genetic testing looks for
mutations in a person’s
chromosomes, genes or
proteins.
Mutations that are harmful
may increase a person’s
risk of developing a
disease such as cancer.
12

11. TYPE OF GENE
• Lynch syndrome (hereditary nonpolyposis colorectal
cancer)
• Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
• Related cancer types: Colorectal, endometrial, ovarian renal
pelvis, pancreatic, small intestine, liver and biliary tract,
stomach, brain, and breast cancers
• Familial adenomatous polyposis
• Gene: APC
• Related cancer types: Colorectal cancer, multiple non-
malignant colon polyps, and both non-cancerous (benign)
and cancerous tumors in the small intestine, brain, stomach,
bone, skin, and other tissues
Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
Related cancer types: Colorectal, endometrial, ovarian, renal
pelvis, pancreatic, small intestine, liver and biliary tract, stomach,
brain, and breast cancers
Gene: APC
Related cancer types: Colorectal cancer, multiple non-malignant
colon polyps, and both non-cancerous (benign) and cancerous
tumors in the small intestine, brain, stomach, bone, skin, and
other tissues
13

12. OBJECTIVE
• General:
• To determine the benefits of genetic testing for screening
colorectal cancer
• Specific:
• To identify effectiveness of cancer genetic testing for
colorectal cancer
• To identify other types of cancer screening tools used for
colorectal cancer
To determine the benefits of genetic testing for screening
colorectal cancer
To identify effectiveness of cancer genetic testing for colorectal
cancer
To identify other types of cancer screening tools used for
colorectal cancer
14

13. METHODS
Search Protocol
• PRISMA statement
• Databases: Scopus and PubMed.
• PICO strategy: Key search terms:
• P: Elderly*/50 to 75 year*/ Between 50 and 75 year* old/
colorectal cancer patients*/ old patients/ old age
• I: Genetic testing/ Genetic screening/ colorectal cancer
screening tool/ colorectal cancer detection/ DNA testing
genome analysis/ DNA sequencing analysis
• C: No comparators
• O: Benefits/ Effectiveness/ important
• The search was restricted only study conducted for the past five
years, 2012 to present.
• English languages.
• The search was done on 24 October 2017.
• Unpublished literatures were not searched
P: Elderly*/50 to 75 year*/ Between 50 and 75 year* old/
colorectal cancer patients*/ old patients/ old age
I: Genetic testing/ Genetic screening/ colorectal cancer
screening tool/ colorectal cancer detection/ DNA testing/
genome analysis/ DNA sequencing analysis
C: No comparators
O: Benefits/ Effectiveness/ important
15

14. METHODS
Selection
• Two stages by a pair of reviewers.
• First stage:
• A pair of reviewers will independently screen part of the
titles and abstracts for inclusion of all the potential studies
that had been identified as a result of the search and code
them as 'retrieve' (eligible or potentially eligible/unclear) or
'do not retrieve'.
• Second stage:
• the full-text study reports/publication will be retrieved & a
pair of reviewers will independently screen the full-text and
identify studies for inclusion
• identify and record reasons for exclusion of the ineligible
studies.
• Any disagreement solved by the third author.
16

15. METHODS
Data extraction
• Standardized form
• Type of article
• Study design
• Country involved
• Target population
• Sampling method, sample size
• Diagnostic method
• Benefit / effectiveness
17

16. RESULTS
Flow of included papers
• The electronic search PubMed and Scopus
• Identification of 43 papers
• Abstract reviews  12 papers related
• Full text review and assessment for eligibility  Total of 6
papers to be excluded
• 37 papers were rejected due to a couple of reasons
• 16 papers – not related to colorectal cancer
• 14 paper – not fulfilled the objective
• 2 paper – review article, not original article
• 5 papers – full article cannot be retrieved
• Total of 6 papers included in the study
16 papers – not related to colorectal cancer
14 paper – not fulfilled the objective
2 paper – review article, not original article
5 papers – full article cannot be retrieved
18

17. LITERATURE SEARCH
BASED ON PRISMA
Records identified through database searching
(n=43)
PUBMED: 29
SCOPUS: 14
Duplicates records removed (n=0)
Level 1 (title and abstract) screened (n=43)
Full text articles assessed for eligibility (n=12)
Studies included for qualitative synthesis (n= 6)
Irrelevant records excluded in the
basic of title and abstract review
(n=31)
Records excluded (n=6)
Reasons:
full article cannot be retrieved
(n=5)
review article, not original article
(n=1)
19

18. RESULTS
Study characteristics
• Data about the following countries:
• 2 USA, 2 Europe, China, Japan
• All studies are original article
• Mostly: cross-sectional study design (4), case control (2).
• Objective:
• Mostly to determine benefit or effectiveness of colorectal
cancer genetic testing
• Some to compare genetic testing with other screening tools
• Diagnostic methods:
• Mostly genetic testing either MSI or genotyping
• Some colonoscopy & SER Spectroscopy.
20

19. STUDY CHARACTERISTICS
6 articles assessing the benefit of genetic testing
2 article comparing with
other screening tool
4 articles assessing the effectiveness of
colorectal cancer genetic testing
Study design
• 2 articles experimental design:
case-control
• No randomized controlled trials
(RCT)
4 observational design: cross-
sectional
21

20. STUDY POPULATION,
LOCATION, SAMPLE SIZE
Study location
2 Europe 2 America Japan China
Study population
• Majority of study population were
colorectal cancer patient with their
relative
some of residents aged 50
years and older
Sample size
• Range from the least: 83 samples & the greatest of samples: 1477 samples
22

21. 23

22. DISCUSSION
The results can provide a sense of relief from
uncertainty and help people make informed
decisions about managing their health care.
It can help diagnose a
genetic condition.
Genetic testing has potential
benefits whether the results
are positive or negative for a
gene mutation.
When a patient has an
accurate diagnosis, the
appropriate treatment can
be given.
Grosse et al, 2012. Bridge et al, 2015.
Johnson et al, 2016
24

23. DISCUSSION
A negative result can eliminate the need for
unnecessary check-ups and screening tests
in some cases.
A positive result can direct a person
toward available prevention,
monitoring and treatment options.
Genetic testing will inform patient or
family members have an increased
risk of developing a condition later in
life.
It will be more
regular follow up
& keep the risk
to a minimum.
Grosse et al, 2012. Marshal et al, 2014.
Walsh et al, 2016
25

24. DISCUSSION
Knowing having an increased risk of having a child
with a genetic condition might give the opportunity
to be more mentally and practically prepared.
Genetic testing able to
inform about human
genetic makeup.
The results of a genetic test
can provide useful
information when planning
for future children.
Neonatal screening can
identify genetic disorders
early in life so treatment
can be started ASAP
Riley et al, 2012. Wang et al, 2014. Vasen et
al, 2016
26

25. RISK
Many of the risks associated with genetic
testing involve the emotional, social or
financial consequences of the test results.
Patient & family members will feel
angry, depressed, anxious or guilty
about their results.
Genetic testing creates tension within
a family because the results can
reveal information about other family
members.
The possibility of genetic
discrimination in
employment or insurance
is also a concern.
Burke et al, 2013. Robson et al, 2014.
William et al, 2016
27

26. • To date, the data on benefit & effectiveness after genetic testing are
reassuring.
• Benefits of screening are likely to outweigh harms for populations at
high risk of colorectal cancer.
• More information is needed about
• the harmful effects of screening,
• the community's responses to screening
• costs of screening for different healthcare systems
• before widespread screening can be recommended.
Conclusion
28

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