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Colorectal cancer in the young, many questions, few answers

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Colorectal cancer in the young

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Colorectal Cancer In The Young

REFERENCES 1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: [PMID: DOI: 10.1002/ijc.25516] 2 American Cancer Society. Global Cancer Facts and Figures. 2nd ed. Atlanta: American Cancer Soc...

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colorectal cancer in the young many questions fe
1 ferlay j shin hr bray f forman d mathers c

Institution Colorectal cancer in the young
Course Colorectal cancer in the young

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Submit a Manuscript: http://www.wjgnet.com/esps/ World J Gastrointest Oncol 2016 June 15; 8(6): 481-488
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1948-5204 (online)
DOI: 10.4251/wjgo.v8.i6.481 © 2016 Baishideng Publishing Group Inc. All rights reserved.

TOPIC HIGHLIGHT

2016 Colorectal Cancer: Global view
Colorectal cancer in the young, many questions, few
answers

Kemal I Deen, Hiroshi Silva, Raeed Deen, Pramodh C Chandrasinghe

Kemal I Deen, Consultant in Colon and Rectal Surgery, The disease predominantly of developed nations, is showing a
Asiri Surgical Hospital, Colombo 11600, Sri Lanka decline in those 50 years of age and older, data from the
West is showing a rising incidence of this cancer in young
Hiroshi Silva, Pramodh C Chandrasinghe, The University of
individuals. Central to this has been the 75% increase
Kelaniya Medical School, Ragama 11600, Sri Lanka
in rectal cancer incidence in the last four decades.
Raeed Deen, The University of Sydney Medical School, Sydney Furthermore, predictive data based on mathematical
NSW 2006, Australia modelling indicates a 124 percent rise in the incidence of
rectal cancer by the year 2030 - a statistic that calls for
Author contributions: All authors equally contributed to this collective global thought and action. While predominance
paper with conception and design, literature review and analysis, of colorectal cancer (CRC) is likely to be in that part of
drafting and critical revision and editing, and final approval of the the large bowel distal to the splenic flexure, which makes
final version.
flexible sigmoidoscopic examination an ideal screening
Conflict-of-interest statement: No potential conflicts of interest tool, the cost and benefit of mass screening in young
relevant to this article were reported. people remain unknown. In countries where the incidence
of young CRC is as high as 35% to 50%, the available
Open-Access: This article is an open-access article which was data do not seem to indicate that the disease in young
selected by an in-house editor and fully peer-reviewed by external people is one of high red meat consuming nations only.
reviewers. It is distributed in accordance with the Creative Improvement in our understanding of genetic pathways
Commons Attribution Non Commercial (CC BY-NC 4.0) license,
in the aetiology of CRC, chiefly of the MSI, CIN and CIMP
which permits others to distribute, remix, adapt, build upon this
work non-commercially, and license their derivative works on pathway, supports the notion that up to 30% of CRC is
different terms, provided the original work is properly cited and genetic, and may reflect a familial trait or environmentally
the use is non-commercial. See: http://creativecommons.org/ induced changes. However, a number of other ger-
licenses/by-nc/4.0/ mline and somatic mutations, some of which remain
unidentified, may play a role in the genesis of this cancer
Correspondence to: Kemal I Deen, MD, MS, FRCS, FACRSI, and stand in the way of a clear understanding of CRC in
FNat, Ac Sci, Consultant in Colon and Rectal Surgery, The the young. Clinically, a proportion of young persons with
Asiri Surgical Hospital, No.21 Kirimandala Mawatha, Colombo
11600, Sri Lanka. CRC die early after curative surgery, presumably from
Telephone: +94-777-746158 aggressive tumour biology, compared with the majority
in whom survival after operation will remain unchanged
Received: January 4, 2016 for five years or greater. The challenge in the future will
Peer-review started: January 5, 2016 be to determine, by genetic fingerprinting or otherwise,
First decision: January 30, 2016 those at risk of developing CRC and the determinants of
Revised: February 29, 2016 survival in those who develop CRC. Ultimately, prevention
Accepted: March 14, 2016
and early detection, just like for those over 50 years
Article in press: March 16, 2016
Published online: June 15, 2016 with CRC, will determine the outcome of CRC in young
persons. At present, aside from those with an established
familial tendency, there is no consensus on screening
young persons who may be at risk. However, increasing
awareness of this cancer in the young and the established
Abstract benefit of prevention in older persons, must be a message
At a time where the incidence of colorectal cancer, a that should be communicated with medical students,

WJGO|www.wjgnet.com 481 June 15, 2016|Volume 8|Issue 6|

, Deen KI et al . Colorectal cancer in the young

primary health care personnel and first contact doctors.
The latter constitutes a formidable challenge.
EPIDEMIOLOGY/PREVALENCE
Historically, CRC in young patients was highest in
Key words: Colon cancer; Young age; Rectal cancer; proportional prevalence from the Asian region. Studies
Colorectal cancer; Young patients; Survival; Early onset have reported a high young cancer prevalence of 38%
in Egypt , 18% in Turkey , 39% in India , 29% in
[7] [8] [9]

© The Author(s) 2016. Published by Baishideng Publishing Nepal , 23% from Saudi Arabia , 19.7% from Sri
[10] [11]

Group Inc. All rights reserved. Lanka , 52% from a single institution in Pakistan and
[12] [13]

10.1% from Taiwan . Most significantly, a recent study
[14]

Core tip: This review of colorectal cancer in the young from the United States , where the authors evaluated
[19]

focuses on new data that reveal CRC to be more a left the records of 393241 patients over a 15-years period,
sided cancer than previously thought and the predicted revealed an overall decline in CRC by 0.92% - the effect
rise by the year 2030. The article outlines the genetics of
attributed to screening. While this was true for those
colorectal cancer (CRC) and discusses limitation in current
over 50 years old with CRC, the study observed an
knowledge in establishing a fingerprint for sporadic CRC.
alarming increase in CRC in those less than 50 years,
Aside from diet in its aetiology, luminal alkalinity and
specifically, in young patients less than 35 years. Using
the colonic microbiome may be contributory and require
further research. The review discusses the need for statistical modelling, the authors predicted an increase
increased awareness of CRC in the young and the need in colon cancer by 90% in patients aged 20 to 34 years
for global consensus on screening young people at risk. and 27.7% in those 35 to 49 years old by the year 2030.
For rectal cancer, the predicted percentage increase in
cancer prevalence for these two age groups was 124.2%
Deen KI, Silva H, Deen R, Chandrasinghe PC. Colorectal cancer and 46% respectively. Gender based analysis of CRC in
in the young, many questions, few answers. World J Gastrointest young patients revealed an equal prevalence in young
Oncol 2016; 8(6): 481-488 Available from: URL: http://www. men and women contradicting the theory that female
[22]

wjgnet.com/1948-5204/full/v8/i6/481.htm DOI: http://dx.doi. hormones are protective of colon and rectal cancer.
org/10.4251/wjgo.v8.i6.481 Furthermore, a 1991 study of young patients in North
America showed that the disease occurred in 34% more
black men and 45% more black women compared with
white Caucasian counterparts . Most young patients
[23]

[22]
INTRODUCTION did not report a family history of CRC; O’Connell et al
Colorectal cancer (CRC) is now the fourth most common revealed that only 23% of young patients with CRC
cause of cancer deaths, with 600000 deaths reported reported the presence of cancer in a family member.
[1,2]
worldwide annually - about 8% of all cancer deaths .
It is the third most common cancer in men and the
FAMILY HISTORY
second most common cancer in women. The sporadic
form, known to affect individuals in their fifth and sixth Contrary to previous knowledge, a current estimate
decades of life , arises from a pre-existing polyp which
[3] of the proportion of CRC likely to have a major here-
[24]
progresses to cancer through the adenoma-dysplasia- ditary component is between 15% and 30% . The
carcinoma sequence; a pathological process which, common heritable syndromes in CRC are either familial
in general, takes five to ten years , and lends itself
[4] adenomatous polyposis (FAP) or hereditary non-
polyposis colorectal cancer (HNPCC)
[25-27]
to prevention by screening . CRC is a disease of de-
[5,6] known to be
veloped nations, and screening by faecal occult blood found in 2 to 5 percent of all patients with CRC. Familial
testing and colonoscopy has stemmed its incidence in adenomatous polyposis is defined by phenotype if an
those over 50 years . By contrast, CRC in the young,
[6] individual has multiple colonic polyps, usually over 100, in
was a disease prevalent in the developing world
[7-14] association with loss of the tumour suppressor gene -the
compared with Australia, New Zealand and the West, adenomatous polyposis coli-APC gene-located on the
long arm of chromosome 5 (5q21) . Most FAP patients
[25]
where its prevalence in young individuals was low
[11,15,16]
.
However, more recently, there has been an increase will develop CRC by age 40 years, while in a minority,
in the number of reports of CRC in the young from the cancer will manifest in the fifth decade or after, due to the
developed world
[17-19]
. This is of concern because the presence of the attenuated FAP gene. In contrast to FAP,
incidence of rectal cancer has risen by 75% in the last HNPCC, first described by Henry Lynch, is characterised
, contributing chiefly to the overall rise in
[20-22]
40 years by the presence of fewer colonic polyps or cancer that is
cancer prevalence. Furthermore, this disease affects indistinguishable from sporadic CRC. In both conditions,
people in the prime of their life, and unlike cancer in which are of autosomal dominant inheritance, family
older individuals, there is limited knowledge about the history is of prime importance. For HNPCC, an affected
aetiology and pathogenesis of CRC in the young. The aim member or members of a family should have had
of this review is to present the current status of CRC in either CRC (Lynch type 1-site specific) or other extra-
the young and to highlight areas for future research. intestinal cancers (Lynch type 2), in association with

WJGO|www.wjgnet.com 482 June 15, 2016|Volume 8|Issue 6|

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