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Colorectal cancer (CRC) is the second most common cancer in Aotearoa New Zealand, second only behind prostate cancer in men and breast cancer in woman. It is the second highest cause of cancer death behind lung cancer, with approximately the same death rate as prostate and breast cancer combined.[[1]] In 2019, there were 3,318 colorectal cancers diagnosed in New Zealand[[1]] and, while the overall the rate is slowly declining, early-onset colorectal cancer (EOCRC), defined as CRC in adults under the age of 50, is on the rise.[[2]] From 1995 to 2012, early-onset rectal cancer in New Zealand men increased by 18%, and by 13% in New Zealand women.[[2]] This pattern is not confined to New Zealand, with increases reported in at least 18 other countries; however, New Zealand is seeing the second fastest increase in incidence in the world.[[3]] Moreover, the increase in EOCRC is occurring independently of late-onset CRC (LOCRC)[[3,5]] and, if current trends continue, it has been estimated that by 2030 1 in 4 rectal cancers diagnosed will be in patients under 50.[[4]]
Figure 1: Colorectal cancer incidence in Aotearoa New Zealand, 1996–2017.[[5]]
Clinical characteristics
EOCRC usually presents in the distal colon (sigmoid) or rectum and, compared to LOCRC, it has several distinct clinical and pathological characteristics. The vast majority (up to 95%) of EOCRC cases present with symptoms,[[6]] the most common being rectal bleeding, change in bowel habit and abdominal pain. These cancers are thought to show more aggressive histopathological characteristics with higher rates of mucinous or signet ring histology and poorly differentiated cancers.[[7]] EOCRC patients are more likely to present with advanced (stage 3 or 4) disease.[[8]]
Delays to diagnosis are reportedly more common in younger patients, ranging from a median time of 217 to 239 days in USA and New Zealand studies, respectively.[[11,12]] In contrast, these studies also report a median time from symptom onset to diagnosis in older patients as 29 and 122 days, respectively.[[11,12]] Moreover, this effect is likely to be larger if under 50s are subdivided out from the under 60s. That young people tend to not seek help when symptoms arise likely contributes to this delay, but another factor is when healthcare professionals do not adequately investigate symptoms in younger patients because they believe they are “too young” to have cancer. This can result in general practitioners (GPs) not referring young patients who are symptomatic, or in those referrals not been accepted by public hospitals despite evidence of rectal bleeding. Delays to CRC diagnosis made up the highest proportion of cancer-related complaints in a Health and Disability Commissioner (HDC) review in 2015, comprising nearly a third of delayed cancer diagnosis complaints.[[9]]
Optimal treatment for EOCRC remains unclear, and current major guidelines do not recommend any different management based on age alone.[[10]] However, studies show EOCRC patients receive more aggressive chemotherapy and radiation therapy regimes at every stage of disease, often without any matched survival benefit. This, in turn, raises concerns that some may be being overtreated, and at risk of harm from unnecessary treatment.[[13,14,16,17]]
The psychosocial impact of EOCRC is also different compared to that of LOCRC. Younger patients are at a different stage of their lives and have different concerns to older patients. This leads to a greater impact on quality of life and concerns around career, financial problems, sexual functioning, family functioning and emotional distress.[[18–22]] This needs to be considered when clinicians are looking after EOCRC patients, routinely enquiring about these issues, with early referral for supports when needed.
What could be driving the increasing incidence of EOCRC?
The exact reason behind the increasing incidence is not known, and it is likely multifactorial. While EOCRC patients do have a higher proportion of germline mutations than commonly seen in older patients, the majority (75–84%) of EOCRC are sporadic.[[23]] A recent study from the Memorial Sloan Kettering Cancer Center found no differences in survival, concluding that “while EOCRC are more commonly left sided…[they] are otherwise clinically and genomically indistinguishable from LOCRC”.[[24]]
The risk factors for LOCRC such as obesity, alcohol, processed meat, sugary drinks, and the “Western diet” (high fat, high meat, and low fibre) may or may not contribute to EOCRC.[[15,30–35]] An individual’s gut microbiome may also play a role. Several bacterial species have already been implicated in adenoma or CRC development.[[25,26]] While data specific to EOCRC are lacking, recent studies suggest the microbiome in patients with EOCRC is different compared that found in patients with LOCRC and healthy controls.[[27,28]] These differences may reflect early-life events and/or ongoing environmental factors, many of which emerged over the past several decades. These include caesarean delivery,[[29]] formula feeding,[[36]] antibiotic use,[[37]] changing diet, synthetic food dyes, MSG high-fructose corn syrup, or perhaps even microplastics.[[38]]
What should be done?
The biggest predictor of survival is the stage of disease at diagnosis; therefore, early detection of EOCRC is crucial.[[8]] The first step to reducing delays to diagnosis is to increase public awareness of symptoms, as exemplified by a recent study where one-third of men were unable to name a single symptom of bowel cancer.[[39]] However, while the “Never Too Young” campaign recently run by Bowel Cancer New Zealand (https://bowelcancernz.org.nz/never-too-young) is helping to increase public awareness of significance symptoms of this disease, there also needs to be timely and adequate investigation once patients present to their GPs seeking help.
New Zealand recently introduced the national bowel cancer screening programme (NBSP), but the 25-year delay to establish this program is considered by many as an embarrassment rather than a success. This program currently only includes individuals over the age of 60, although this is being lowered to 50 for Māori patients to address the inequity caused with a higher proportion of Māori patients with bowel cancer presenting before the age of 60.[[40]] While this is a very welcome move, New Zealand is still behind many other Organisation for Economic Co-operation and Development (OECD) countries with the British National Health Service (NHS),[[41]] Australia,[[42]] Canada[[43]] and Germany,[[44]] all offering bowel screening from the age of 50. Germany has been doing this for the past 20 years.[[44]] The USA preventative task force guidelines for bowel cancer screening have recently recommended to reduce screening age to 45.[[45,46]]
Alongside lowering the screening age, timely access to colonoscopy for symptomatic young patients needs to be improved. In the future, as our technology and knowledge of drivers for EOCRC improves, we may be able to selectively screen higher-risk patients based on faecal testing, polygenic risk scores and presence of known risk factors.
There is concern that our already struggling health system cannot accommodate increasing demand for colonoscopy and New Zealand has a shortage of colonoscopists, gastroenterologists[[47,48]] and surgeons. However, failure to recognise the changing epidemiology of the disease, the impact this will have on changing our clinical behaviour, and the need to incorporate this impact into health planning will only make matters worse.
Summary
Abstract
Aim
Method
Results
Conclusion
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1) New cancer registrations 2019 | Ministry of Health NZ [Internet]. [cited 2022 Sep 12]. Available from: https://www.health.govt.nz/publication/new-cancer-registrations-2019.
2) Gandhi J, Davidson C, Hall C, Pearson J, Eglinton T, Wakeman C, et al. Population-based study demonstrating an increase in colorectal cancer in young patients. Br J Surgery. 2017 Jul 1;104(8):1063-8.
3) Siegel RL, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut [Internet]. 2019;68:2179-85. Available from: http://dx.doi.org/10.1136/gutjnl-2019-319511.
4) Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1) doi:10.1001/ jamasurg.2014.1756. 2015. p. 17-22.
5) te Aho o Te Kahu. He Pūrongo Mate Pukupuku o Aotearoa 2020, The State of Cancer in New Zealand 2020. (revised march 2021) [Internet]. Te Aho o Te Kahu, Cancer control agency. 2021 [cited 2022 Sep 26]. Available from: https://teaho.govt.nz/reports/cancer-state.
6) Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar 1;7(3):262-74.
7) O’Connell JB, Maggard MA, Liu JH, Etzioni DA, Livingston EH, Ko CY. Do Young Colon Cancer Patients Have Worse Outcomes?. 2004; Available from: www.seer.cancer.gov/seerstat.
8) Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer [Internet]. 2016 Mar 15 [cited 2022 Jul 8];122(6):929-34. Available from: https://onlinelibrary-wiley-com.ezproxy.surgeons.org/doi/full/10.1002/cncr.29716.
9) Royal New Zealand College of General Practitioners. Delayed diagnosis of cancer: in perspective. Policy brief. RNZCGP.org. 2015.
10) NCCN guidelines 2022. Treatment by Cancer Type [Internet]. [cited 2022 Sep 13]. Available from: https://www.nccn.org/guidelines/category_1.
11) Scott RB, Rangel LE, Osler TM, Hyman NH. Rectal cancer in patients under the age of 50 years: the delayed diagnosis. Am J Surg [Internet]. 2016 Jun 1 [cited 2021 Sep 2];211(6):1014-8. Available from: http://www.americanjournalofsurgery.com/article/S0002961015005942/fulltext.
12) Blackmore T, Lao C, Chepulis L, Page B, Lawrenson R. The characteristics and outcomes of patients with colorectal cancer in New Zealand, analysed by Cancer Network. N Z Med J. 2020;133(1513):42-52.
13) Kolarich A, George TJ, Hughes SJ, Delitto D, Allegra CJ, et al. Rectal Cancer Patients Younger Than 50 Years Lack a Survival Benefit From NCCN Guideline-Directed Treatment for Stage II and III Disease. Cancer. 2018 Sep 1;124(17):3510-3519. doi: 10.1002/cncr.31527.
14) O’Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, et al. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol and Hepatol. W.B. Saunders; 2021.
15) Kneuertz PJ, Chang GJ, Hu CY, Rodriguez-Bigas MA, Eng C, Vilar ; Eduardo, et al. Overtreatment of Young Adults With Colon Cancer More Intense Treatments With Unmatched Survival Gains. JAMA Surg [Internet]. 2015;150(5):402-9. Available from: https://jamanetwork.com/.
16) Bliggenstorfer JT, Bingmer K, Ofshteyn A, Stein SL, Charles R, Steinhagen E. Neoadjuvant radiation above NCCN guidelines for rectal cancer is associated with age under 50 and early clinical stage. Surg Endosc [Internet]. 2022;36:2925-35. Available from: https://doi.org/10.1007/s00464-021-08585-w.
17) Burnett-Hartman AN, David Powers · J, Chubak J, Corley DA, Ghai NR, Carmit ·, et al. Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network. Cancer Causes & Control [Internet]. 2019 [cited 2022 Sep 13];30:747-55. Available from: https://doi.org/10.1007/s10552-019-01181-3.
18) Downing A, Morris EJAEJA, Richards M, Corner J, Wright P, Sebag-Montefiore D, et al. Health-related quality of life after colorectal cancer in England: A patient-reported outcomes study of individuals 12 to 36 months after diagnosis. J Clin Oncol. 2015 Feb 20;33(6):616-24.
19) Mack JW, Cronin A, Fasciano K, Block SD, Keating NL. Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age. Psychooncology [Internet]. 2016 Sep 1 [cited 2022 Apr 21];1091(September 2015):1085-91. Available from: /pmc/articles/PMC4775442/.
20) de Wind A, Tamminga SJSJ, Bony CAGCAG, Diether M, Ludwig MAM, Velthuis MJMJ, et al. Loss of paid employment up to 4 years after colorectal cancer diagnosis—a nationwide register-based study with a population-based reference group. Cancers (Basel). 2021;13(12):2868.
21) Adams S v., Ceballos R, Newcomb PA. Quality of life and mortality of long-term colorectal cancer survivors in the seattle colorectal cancer family registry. PLoS One. 2016 Jun 1;11(6).
22) Seguin L, Touzani R, Bouhnik ADAD, Charif ABAB, Marino P, Bendiane MKMK, et al. Deterioration of sexual health in cancer survivors five years after diagnosis: Data from the french national prospective vican survey. Cancers (Basel) [Internet]. 2020;12(11):1-21. Available from: www.mdpi.com/journal/cancers.
23) Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. N Engl J Med. 2022 Apr 21;386(16):1547-58.
24) Cercek A, Chatila WK, Yaeger R, Walch H, Fernandes GDS, Krishnan A, etal. A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers. J Natl Cancer Inst. 2021 Aug 18;113(12):1683–92. doi: 10.1093/jnci/djab124. Epub ahead of print. PMID: 34405229; PMCID: PMC8634406.
25) Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol [Internet]. 2019; Available from: https://doi.org/10.1038/.
26) Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017 Feb 2; 12(2):e0171602. doi:10.1371/journal.pone.0171602.
27) Abdullah M, Sukartini Saskia Aziza Nursyirwan Rabbinu Rangga Pribadi Hasan Maulahela Amanda Pitarini Utari Virly Nanda Muzellina Agustinus Wiraatmadja Kaka Renaldi N. Gut Microbiota Profiles in Early- and Late-Onset Colorectal Cancer: A Potential Diagnostic Biomarker in the Future. Digestion [Internet]. 2021;102:823-32. Available from: www.karger.com/dig.
28) Kong C, Liang L, Liu G, Du L, Yang Y, Liu J, et al. Gut microbiota Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer. Gut. 2022;0:1-14.
29) Sandall J, Tribe RM, Avery L, Mola G, Visser GH, Homer CS, et al. Short-term and long-term effects of caesarean section on the health of women and children. The Lancet. 2018 Oct 13;392(10155):1349-57.
30) Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M, et al. Association of Obesity with Risk of Early-Onset Colorectal Cancer among Women. JAMA Oncol. 2019 Jan 1;5(1):37-44.
31) Hur J, Otegbeye E, Joh HK, Nimptsch K, Ng K, Ogino S, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021 Dec 1;70(12):2330-6.
32) Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine [Internet]. 2022 Jul 1 [cited 2022 Aug 31];49:101460. Available from: http://www.thelancet.com/article/S2589537022001900/fulltext.
33) Low EE, Demb J, Liu L, Earles A, Bustamante R, Williams CD, et al. Risk Factors for Early-Onset Colorectal Cancer. Gastroenterol [Internet]. 2020;159(2):492-501.e7. Available from: https://doi.org/10.1053/j.gastro.2020.01.004.
34) Carroll KL, Frugé AD, Heslin MJ, Lipke EA, Greene MW. Diet as a Risk Factor for Early-Onset Colorectal Adenoma and Carcinoma: A Systematic Review. Front Nutr [Internet]. 2022 Jun 9 [cited 2022 Jul 8];9. Available from: https://pubmed.ncbi.nlm.nih.gov/35757246/.
35) Li H, Boakye D, Chen X, Hoffmeister M, Brenner H. Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis. 2021; Available from: http://links.lww.com/AJG/C128,http://links.lww.com/AJG/C129,http://links.lww.com/AJG/C130,http://links.lww.com/AJG/C131AmJGastroenterol2021;116:2173-2183.https://doi.org/10.14309/ajg.0000000000001393.
36) Farver M, smilowitz J. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants Supplementary Issue: Parental Nutritional Metabolism and Health and Disease of Offspring. Nutr Metab Insights [Internet]. 2015(8). Available from: http://www.cdc.gov/breastfeeding/.
37) McDowell R, Perrott S, Murchie P, Cardwell C, Hughes C, Samuel L. Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database. Br J Cancer 2021 126:6 [Internet]. 2021 Dec 17 [cited 2022 Aug 31];126(6):957-67. Available from: https://www.nature.com/articles/s41416-021-01665-7.
38) Hofseth LJ, Hebert JR, Chanda A, Chen H, Love BL, Pena MM, et al. Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol [Internet]. [cited 2022 Apr 12]; Available from: https://doi.org/10.1038/.
39) Thomas RJS, Clarke VA. Community (mis) understanding of colorectal cancer treatment. Aust N Z J Surg [Internet]. 1998 May [cited 2022 Jul 1];68(5):328-30. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1445-2197.1998.tb04764.x.
40) Bowel screening age for Māori and Pasifika lowered - Bowel Cancer NZ [Internet]. [cited 2022 Sep 12]. Available from: https://bowelcancernz.org.nz/new/bowel-screening-age-for-maori-and-pasifika-lowered/.
41) Bowel cancer screening - NHS [Internet]. [cited 2022 Sep 13]. Available from: https://www.nhs.uk/conditions/bowel-cancer-screening/.
42) National Bowel Cancer Screening Program | Australian Government Department of Health and Aged Care [Internet]. [cited 2022 Sep 13]. Available from: https://www.health.gov.au/initiatives-and-programs/national-bowel-cancer-screening-program.
43) Screening for colorectal cancer | Canadian Cancer Society [Internet]. [cited 2022 Sep 13]. Available from: https://cancer.ca/en/cancer-information/cancer-types/colorectal/screening.
44) Niedermaier T, Balavarca Y, Brenner H. Screening for Colorectal Cancer - A German Perspective. Vol. 116, American Journal of Gastroenterology. Wolters Kluwer Health; 2021. p. 841.
45) Knudsen AB, Rutter CM, Peterse EFP, Lietz AP, Seguin CL, Meester RGS, et al. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Colorectal Cancer Screening: An Updated Decision Analysis for the US Preventive Services Task Force [Internet]. 2021 [cited 2022 Sep 13]; (AHRQ Publication No. 20-05271-EF-2). Available from: https://www.ncbi.nlm.nih.gov/books/NBK570833/.
46) Medical Association A. Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement. 2021; Available from: https://jamanetwork.com/.
47) Stamm R, Aluzaite K, Arnold M, Caspritz T, White C, Schultz M. Challenges for the future: the gastroenterology specialist workforce in New Zealand. N Z Med J [Internet]. 2020 [cited 2022 Sep 12];133:1519. Available from: www.nzma.org.nz/journal.
48) A Critical Analysis of the gastroenterology specialist workforce in New Zealand | New Zealand Doctor [Internet]. [cited 2022 Sep 12]. Available from: https://www.nzdoctor.co.nz/article/undoctored/critical-analysis-gastroenterology-specialist-workforce-new-zealand.
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Colorectal cancer (CRC) is the second most common cancer in Aotearoa New Zealand, second only behind prostate cancer in men and breast cancer in woman. It is the second highest cause of cancer death behind lung cancer, with approximately the same death rate as prostate and breast cancer combined.[[1]] In 2019, there were 3,318 colorectal cancers diagnosed in New Zealand[[1]] and, while the overall the rate is slowly declining, early-onset colorectal cancer (EOCRC), defined as CRC in adults under the age of 50, is on the rise.[[2]] From 1995 to 2012, early-onset rectal cancer in New Zealand men increased by 18%, and by 13% in New Zealand women.[[2]] This pattern is not confined to New Zealand, with increases reported in at least 18 other countries; however, New Zealand is seeing the second fastest increase in incidence in the world.[[3]] Moreover, the increase in EOCRC is occurring independently of late-onset CRC (LOCRC)[[3,5]] and, if current trends continue, it has been estimated that by 2030 1 in 4 rectal cancers diagnosed will be in patients under 50.[[4]]
Figure 1: Colorectal cancer incidence in Aotearoa New Zealand, 1996–2017.[[5]]
Clinical characteristics
EOCRC usually presents in the distal colon (sigmoid) or rectum and, compared to LOCRC, it has several distinct clinical and pathological characteristics. The vast majority (up to 95%) of EOCRC cases present with symptoms,[[6]] the most common being rectal bleeding, change in bowel habit and abdominal pain. These cancers are thought to show more aggressive histopathological characteristics with higher rates of mucinous or signet ring histology and poorly differentiated cancers.[[7]] EOCRC patients are more likely to present with advanced (stage 3 or 4) disease.[[8]]
Delays to diagnosis are reportedly more common in younger patients, ranging from a median time of 217 to 239 days in USA and New Zealand studies, respectively.[[11,12]] In contrast, these studies also report a median time from symptom onset to diagnosis in older patients as 29 and 122 days, respectively.[[11,12]] Moreover, this effect is likely to be larger if under 50s are subdivided out from the under 60s. That young people tend to not seek help when symptoms arise likely contributes to this delay, but another factor is when healthcare professionals do not adequately investigate symptoms in younger patients because they believe they are “too young” to have cancer. This can result in general practitioners (GPs) not referring young patients who are symptomatic, or in those referrals not been accepted by public hospitals despite evidence of rectal bleeding. Delays to CRC diagnosis made up the highest proportion of cancer-related complaints in a Health and Disability Commissioner (HDC) review in 2015, comprising nearly a third of delayed cancer diagnosis complaints.[[9]]
Optimal treatment for EOCRC remains unclear, and current major guidelines do not recommend any different management based on age alone.[[10]] However, studies show EOCRC patients receive more aggressive chemotherapy and radiation therapy regimes at every stage of disease, often without any matched survival benefit. This, in turn, raises concerns that some may be being overtreated, and at risk of harm from unnecessary treatment.[[13,14,16,17]]
The psychosocial impact of EOCRC is also different compared to that of LOCRC. Younger patients are at a different stage of their lives and have different concerns to older patients. This leads to a greater impact on quality of life and concerns around career, financial problems, sexual functioning, family functioning and emotional distress.[[18–22]] This needs to be considered when clinicians are looking after EOCRC patients, routinely enquiring about these issues, with early referral for supports when needed.
What could be driving the increasing incidence of EOCRC?
The exact reason behind the increasing incidence is not known, and it is likely multifactorial. While EOCRC patients do have a higher proportion of germline mutations than commonly seen in older patients, the majority (75–84%) of EOCRC are sporadic.[[23]] A recent study from the Memorial Sloan Kettering Cancer Center found no differences in survival, concluding that “while EOCRC are more commonly left sided…[they] are otherwise clinically and genomically indistinguishable from LOCRC”.[[24]]
The risk factors for LOCRC such as obesity, alcohol, processed meat, sugary drinks, and the “Western diet” (high fat, high meat, and low fibre) may or may not contribute to EOCRC.[[15,30–35]] An individual’s gut microbiome may also play a role. Several bacterial species have already been implicated in adenoma or CRC development.[[25,26]] While data specific to EOCRC are lacking, recent studies suggest the microbiome in patients with EOCRC is different compared that found in patients with LOCRC and healthy controls.[[27,28]] These differences may reflect early-life events and/or ongoing environmental factors, many of which emerged over the past several decades. These include caesarean delivery,[[29]] formula feeding,[[36]] antibiotic use,[[37]] changing diet, synthetic food dyes, MSG high-fructose corn syrup, or perhaps even microplastics.[[38]]
What should be done?
The biggest predictor of survival is the stage of disease at diagnosis; therefore, early detection of EOCRC is crucial.[[8]] The first step to reducing delays to diagnosis is to increase public awareness of symptoms, as exemplified by a recent study where one-third of men were unable to name a single symptom of bowel cancer.[[39]] However, while the “Never Too Young” campaign recently run by Bowel Cancer New Zealand (https://bowelcancernz.org.nz/never-too-young) is helping to increase public awareness of significance symptoms of this disease, there also needs to be timely and adequate investigation once patients present to their GPs seeking help.
New Zealand recently introduced the national bowel cancer screening programme (NBSP), but the 25-year delay to establish this program is considered by many as an embarrassment rather than a success. This program currently only includes individuals over the age of 60, although this is being lowered to 50 for Māori patients to address the inequity caused with a higher proportion of Māori patients with bowel cancer presenting before the age of 60.[[40]] While this is a very welcome move, New Zealand is still behind many other Organisation for Economic Co-operation and Development (OECD) countries with the British National Health Service (NHS),[[41]] Australia,[[42]] Canada[[43]] and Germany,[[44]] all offering bowel screening from the age of 50. Germany has been doing this for the past 20 years.[[44]] The USA preventative task force guidelines for bowel cancer screening have recently recommended to reduce screening age to 45.[[45,46]]
Alongside lowering the screening age, timely access to colonoscopy for symptomatic young patients needs to be improved. In the future, as our technology and knowledge of drivers for EOCRC improves, we may be able to selectively screen higher-risk patients based on faecal testing, polygenic risk scores and presence of known risk factors.
There is concern that our already struggling health system cannot accommodate increasing demand for colonoscopy and New Zealand has a shortage of colonoscopists, gastroenterologists[[47,48]] and surgeons. However, failure to recognise the changing epidemiology of the disease, the impact this will have on changing our clinical behaviour, and the need to incorporate this impact into health planning will only make matters worse.
Summary
Abstract
Aim
Method
Results
Conclusion
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1) New cancer registrations 2019 | Ministry of Health NZ [Internet]. [cited 2022 Sep 12]. Available from: https://www.health.govt.nz/publication/new-cancer-registrations-2019.
2) Gandhi J, Davidson C, Hall C, Pearson J, Eglinton T, Wakeman C, et al. Population-based study demonstrating an increase in colorectal cancer in young patients. Br J Surgery. 2017 Jul 1;104(8):1063-8.
3) Siegel RL, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut [Internet]. 2019;68:2179-85. Available from: http://dx.doi.org/10.1136/gutjnl-2019-319511.
4) Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1) doi:10.1001/ jamasurg.2014.1756. 2015. p. 17-22.
5) te Aho o Te Kahu. He Pūrongo Mate Pukupuku o Aotearoa 2020, The State of Cancer in New Zealand 2020. (revised march 2021) [Internet]. Te Aho o Te Kahu, Cancer control agency. 2021 [cited 2022 Sep 26]. Available from: https://teaho.govt.nz/reports/cancer-state.
6) Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar 1;7(3):262-74.
7) O’Connell JB, Maggard MA, Liu JH, Etzioni DA, Livingston EH, Ko CY. Do Young Colon Cancer Patients Have Worse Outcomes?. 2004; Available from: www.seer.cancer.gov/seerstat.
8) Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer [Internet]. 2016 Mar 15 [cited 2022 Jul 8];122(6):929-34. Available from: https://onlinelibrary-wiley-com.ezproxy.surgeons.org/doi/full/10.1002/cncr.29716.
9) Royal New Zealand College of General Practitioners. Delayed diagnosis of cancer: in perspective. Policy brief. RNZCGP.org. 2015.
10) NCCN guidelines 2022. Treatment by Cancer Type [Internet]. [cited 2022 Sep 13]. Available from: https://www.nccn.org/guidelines/category_1.
11) Scott RB, Rangel LE, Osler TM, Hyman NH. Rectal cancer in patients under the age of 50 years: the delayed diagnosis. Am J Surg [Internet]. 2016 Jun 1 [cited 2021 Sep 2];211(6):1014-8. Available from: http://www.americanjournalofsurgery.com/article/S0002961015005942/fulltext.
12) Blackmore T, Lao C, Chepulis L, Page B, Lawrenson R. The characteristics and outcomes of patients with colorectal cancer in New Zealand, analysed by Cancer Network. N Z Med J. 2020;133(1513):42-52.
13) Kolarich A, George TJ, Hughes SJ, Delitto D, Allegra CJ, et al. Rectal Cancer Patients Younger Than 50 Years Lack a Survival Benefit From NCCN Guideline-Directed Treatment for Stage II and III Disease. Cancer. 2018 Sep 1;124(17):3510-3519. doi: 10.1002/cncr.31527.
14) O’Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, et al. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol and Hepatol. W.B. Saunders; 2021.
15) Kneuertz PJ, Chang GJ, Hu CY, Rodriguez-Bigas MA, Eng C, Vilar ; Eduardo, et al. Overtreatment of Young Adults With Colon Cancer More Intense Treatments With Unmatched Survival Gains. JAMA Surg [Internet]. 2015;150(5):402-9. Available from: https://jamanetwork.com/.
16) Bliggenstorfer JT, Bingmer K, Ofshteyn A, Stein SL, Charles R, Steinhagen E. Neoadjuvant radiation above NCCN guidelines for rectal cancer is associated with age under 50 and early clinical stage. Surg Endosc [Internet]. 2022;36:2925-35. Available from: https://doi.org/10.1007/s00464-021-08585-w.
17) Burnett-Hartman AN, David Powers · J, Chubak J, Corley DA, Ghai NR, Carmit ·, et al. Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network. Cancer Causes & Control [Internet]. 2019 [cited 2022 Sep 13];30:747-55. Available from: https://doi.org/10.1007/s10552-019-01181-3.
18) Downing A, Morris EJAEJA, Richards M, Corner J, Wright P, Sebag-Montefiore D, et al. Health-related quality of life after colorectal cancer in England: A patient-reported outcomes study of individuals 12 to 36 months after diagnosis. J Clin Oncol. 2015 Feb 20;33(6):616-24.
19) Mack JW, Cronin A, Fasciano K, Block SD, Keating NL. Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age. Psychooncology [Internet]. 2016 Sep 1 [cited 2022 Apr 21];1091(September 2015):1085-91. Available from: /pmc/articles/PMC4775442/.
20) de Wind A, Tamminga SJSJ, Bony CAGCAG, Diether M, Ludwig MAM, Velthuis MJMJ, et al. Loss of paid employment up to 4 years after colorectal cancer diagnosis—a nationwide register-based study with a population-based reference group. Cancers (Basel). 2021;13(12):2868.
21) Adams S v., Ceballos R, Newcomb PA. Quality of life and mortality of long-term colorectal cancer survivors in the seattle colorectal cancer family registry. PLoS One. 2016 Jun 1;11(6).
22) Seguin L, Touzani R, Bouhnik ADAD, Charif ABAB, Marino P, Bendiane MKMK, et al. Deterioration of sexual health in cancer survivors five years after diagnosis: Data from the french national prospective vican survey. Cancers (Basel) [Internet]. 2020;12(11):1-21. Available from: www.mdpi.com/journal/cancers.
23) Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. N Engl J Med. 2022 Apr 21;386(16):1547-58.
24) Cercek A, Chatila WK, Yaeger R, Walch H, Fernandes GDS, Krishnan A, etal. A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers. J Natl Cancer Inst. 2021 Aug 18;113(12):1683–92. doi: 10.1093/jnci/djab124. Epub ahead of print. PMID: 34405229; PMCID: PMC8634406.
25) Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol [Internet]. 2019; Available from: https://doi.org/10.1038/.
26) Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017 Feb 2; 12(2):e0171602. doi:10.1371/journal.pone.0171602.
27) Abdullah M, Sukartini Saskia Aziza Nursyirwan Rabbinu Rangga Pribadi Hasan Maulahela Amanda Pitarini Utari Virly Nanda Muzellina Agustinus Wiraatmadja Kaka Renaldi N. Gut Microbiota Profiles in Early- and Late-Onset Colorectal Cancer: A Potential Diagnostic Biomarker in the Future. Digestion [Internet]. 2021;102:823-32. Available from: www.karger.com/dig.
28) Kong C, Liang L, Liu G, Du L, Yang Y, Liu J, et al. Gut microbiota Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer. Gut. 2022;0:1-14.
29) Sandall J, Tribe RM, Avery L, Mola G, Visser GH, Homer CS, et al. Short-term and long-term effects of caesarean section on the health of women and children. The Lancet. 2018 Oct 13;392(10155):1349-57.
30) Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M, et al. Association of Obesity with Risk of Early-Onset Colorectal Cancer among Women. JAMA Oncol. 2019 Jan 1;5(1):37-44.
31) Hur J, Otegbeye E, Joh HK, Nimptsch K, Ng K, Ogino S, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021 Dec 1;70(12):2330-6.
32) Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine [Internet]. 2022 Jul 1 [cited 2022 Aug 31];49:101460. Available from: http://www.thelancet.com/article/S2589537022001900/fulltext.
33) Low EE, Demb J, Liu L, Earles A, Bustamante R, Williams CD, et al. Risk Factors for Early-Onset Colorectal Cancer. Gastroenterol [Internet]. 2020;159(2):492-501.e7. Available from: https://doi.org/10.1053/j.gastro.2020.01.004.
34) Carroll KL, Frugé AD, Heslin MJ, Lipke EA, Greene MW. Diet as a Risk Factor for Early-Onset Colorectal Adenoma and Carcinoma: A Systematic Review. Front Nutr [Internet]. 2022 Jun 9 [cited 2022 Jul 8];9. Available from: https://pubmed.ncbi.nlm.nih.gov/35757246/.
35) Li H, Boakye D, Chen X, Hoffmeister M, Brenner H. Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis. 2021; Available from: http://links.lww.com/AJG/C128,http://links.lww.com/AJG/C129,http://links.lww.com/AJG/C130,http://links.lww.com/AJG/C131AmJGastroenterol2021;116:2173-2183.https://doi.org/10.14309/ajg.0000000000001393.
36) Farver M, smilowitz J. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants Supplementary Issue: Parental Nutritional Metabolism and Health and Disease of Offspring. Nutr Metab Insights [Internet]. 2015(8). Available from: http://www.cdc.gov/breastfeeding/.
37) McDowell R, Perrott S, Murchie P, Cardwell C, Hughes C, Samuel L. Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database. Br J Cancer 2021 126:6 [Internet]. 2021 Dec 17 [cited 2022 Aug 31];126(6):957-67. Available from: https://www.nature.com/articles/s41416-021-01665-7.
38) Hofseth LJ, Hebert JR, Chanda A, Chen H, Love BL, Pena MM, et al. Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol [Internet]. [cited 2022 Apr 12]; Available from: https://doi.org/10.1038/.
39) Thomas RJS, Clarke VA. Community (mis) understanding of colorectal cancer treatment. Aust N Z J Surg [Internet]. 1998 May [cited 2022 Jul 1];68(5):328-30. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1445-2197.1998.tb04764.x.
40) Bowel screening age for Māori and Pasifika lowered - Bowel Cancer NZ [Internet]. [cited 2022 Sep 12]. Available from: https://bowelcancernz.org.nz/new/bowel-screening-age-for-maori-and-pasifika-lowered/.
41) Bowel cancer screening - NHS [Internet]. [cited 2022 Sep 13]. Available from: https://www.nhs.uk/conditions/bowel-cancer-screening/.
42) National Bowel Cancer Screening Program | Australian Government Department of Health and Aged Care [Internet]. [cited 2022 Sep 13]. Available from: https://www.health.gov.au/initiatives-and-programs/national-bowel-cancer-screening-program.
43) Screening for colorectal cancer | Canadian Cancer Society [Internet]. [cited 2022 Sep 13]. Available from: https://cancer.ca/en/cancer-information/cancer-types/colorectal/screening.
44) Niedermaier T, Balavarca Y, Brenner H. Screening for Colorectal Cancer - A German Perspective. Vol. 116, American Journal of Gastroenterology. Wolters Kluwer Health; 2021. p. 841.
45) Knudsen AB, Rutter CM, Peterse EFP, Lietz AP, Seguin CL, Meester RGS, et al. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Colorectal Cancer Screening: An Updated Decision Analysis for the US Preventive Services Task Force [Internet]. 2021 [cited 2022 Sep 13]; (AHRQ Publication No. 20-05271-EF-2). Available from: https://www.ncbi.nlm.nih.gov/books/NBK570833/.
46) Medical Association A. Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement. 2021; Available from: https://jamanetwork.com/.
47) Stamm R, Aluzaite K, Arnold M, Caspritz T, White C, Schultz M. Challenges for the future: the gastroenterology specialist workforce in New Zealand. N Z Med J [Internet]. 2020 [cited 2022 Sep 12];133:1519. Available from: www.nzma.org.nz/journal.
48) A Critical Analysis of the gastroenterology specialist workforce in New Zealand | New Zealand Doctor [Internet]. [cited 2022 Sep 12]. Available from: https://www.nzdoctor.co.nz/article/undoctored/critical-analysis-gastroenterology-specialist-workforce-new-zealand.
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Colorectal cancer (CRC) is the second most common cancer in Aotearoa New Zealand, second only behind prostate cancer in men and breast cancer in woman. It is the second highest cause of cancer death behind lung cancer, with approximately the same death rate as prostate and breast cancer combined.[[1]] In 2019, there were 3,318 colorectal cancers diagnosed in New Zealand[[1]] and, while the overall the rate is slowly declining, early-onset colorectal cancer (EOCRC), defined as CRC in adults under the age of 50, is on the rise.[[2]] From 1995 to 2012, early-onset rectal cancer in New Zealand men increased by 18%, and by 13% in New Zealand women.[[2]] This pattern is not confined to New Zealand, with increases reported in at least 18 other countries; however, New Zealand is seeing the second fastest increase in incidence in the world.[[3]] Moreover, the increase in EOCRC is occurring independently of late-onset CRC (LOCRC)[[3,5]] and, if current trends continue, it has been estimated that by 2030 1 in 4 rectal cancers diagnosed will be in patients under 50.[[4]]
Figure 1: Colorectal cancer incidence in Aotearoa New Zealand, 1996–2017.[[5]]
Clinical characteristics
EOCRC usually presents in the distal colon (sigmoid) or rectum and, compared to LOCRC, it has several distinct clinical and pathological characteristics. The vast majority (up to 95%) of EOCRC cases present with symptoms,[[6]] the most common being rectal bleeding, change in bowel habit and abdominal pain. These cancers are thought to show more aggressive histopathological characteristics with higher rates of mucinous or signet ring histology and poorly differentiated cancers.[[7]] EOCRC patients are more likely to present with advanced (stage 3 or 4) disease.[[8]]
Delays to diagnosis are reportedly more common in younger patients, ranging from a median time of 217 to 239 days in USA and New Zealand studies, respectively.[[11,12]] In contrast, these studies also report a median time from symptom onset to diagnosis in older patients as 29 and 122 days, respectively.[[11,12]] Moreover, this effect is likely to be larger if under 50s are subdivided out from the under 60s. That young people tend to not seek help when symptoms arise likely contributes to this delay, but another factor is when healthcare professionals do not adequately investigate symptoms in younger patients because they believe they are “too young” to have cancer. This can result in general practitioners (GPs) not referring young patients who are symptomatic, or in those referrals not been accepted by public hospitals despite evidence of rectal bleeding. Delays to CRC diagnosis made up the highest proportion of cancer-related complaints in a Health and Disability Commissioner (HDC) review in 2015, comprising nearly a third of delayed cancer diagnosis complaints.[[9]]
Optimal treatment for EOCRC remains unclear, and current major guidelines do not recommend any different management based on age alone.[[10]] However, studies show EOCRC patients receive more aggressive chemotherapy and radiation therapy regimes at every stage of disease, often without any matched survival benefit. This, in turn, raises concerns that some may be being overtreated, and at risk of harm from unnecessary treatment.[[13,14,16,17]]
The psychosocial impact of EOCRC is also different compared to that of LOCRC. Younger patients are at a different stage of their lives and have different concerns to older patients. This leads to a greater impact on quality of life and concerns around career, financial problems, sexual functioning, family functioning and emotional distress.[[18–22]] This needs to be considered when clinicians are looking after EOCRC patients, routinely enquiring about these issues, with early referral for supports when needed.
What could be driving the increasing incidence of EOCRC?
The exact reason behind the increasing incidence is not known, and it is likely multifactorial. While EOCRC patients do have a higher proportion of germline mutations than commonly seen in older patients, the majority (75–84%) of EOCRC are sporadic.[[23]] A recent study from the Memorial Sloan Kettering Cancer Center found no differences in survival, concluding that “while EOCRC are more commonly left sided…[they] are otherwise clinically and genomically indistinguishable from LOCRC”.[[24]]
The risk factors for LOCRC such as obesity, alcohol, processed meat, sugary drinks, and the “Western diet” (high fat, high meat, and low fibre) may or may not contribute to EOCRC.[[15,30–35]] An individual’s gut microbiome may also play a role. Several bacterial species have already been implicated in adenoma or CRC development.[[25,26]] While data specific to EOCRC are lacking, recent studies suggest the microbiome in patients with EOCRC is different compared that found in patients with LOCRC and healthy controls.[[27,28]] These differences may reflect early-life events and/or ongoing environmental factors, many of which emerged over the past several decades. These include caesarean delivery,[[29]] formula feeding,[[36]] antibiotic use,[[37]] changing diet, synthetic food dyes, MSG high-fructose corn syrup, or perhaps even microplastics.[[38]]
What should be done?
The biggest predictor of survival is the stage of disease at diagnosis; therefore, early detection of EOCRC is crucial.[[8]] The first step to reducing delays to diagnosis is to increase public awareness of symptoms, as exemplified by a recent study where one-third of men were unable to name a single symptom of bowel cancer.[[39]] However, while the “Never Too Young” campaign recently run by Bowel Cancer New Zealand (https://bowelcancernz.org.nz/never-too-young) is helping to increase public awareness of significance symptoms of this disease, there also needs to be timely and adequate investigation once patients present to their GPs seeking help.
New Zealand recently introduced the national bowel cancer screening programme (NBSP), but the 25-year delay to establish this program is considered by many as an embarrassment rather than a success. This program currently only includes individuals over the age of 60, although this is being lowered to 50 for Māori patients to address the inequity caused with a higher proportion of Māori patients with bowel cancer presenting before the age of 60.[[40]] While this is a very welcome move, New Zealand is still behind many other Organisation for Economic Co-operation and Development (OECD) countries with the British National Health Service (NHS),[[41]] Australia,[[42]] Canada[[43]] and Germany,[[44]] all offering bowel screening from the age of 50. Germany has been doing this for the past 20 years.[[44]] The USA preventative task force guidelines for bowel cancer screening have recently recommended to reduce screening age to 45.[[45,46]]
Alongside lowering the screening age, timely access to colonoscopy for symptomatic young patients needs to be improved. In the future, as our technology and knowledge of drivers for EOCRC improves, we may be able to selectively screen higher-risk patients based on faecal testing, polygenic risk scores and presence of known risk factors.
There is concern that our already struggling health system cannot accommodate increasing demand for colonoscopy and New Zealand has a shortage of colonoscopists, gastroenterologists[[47,48]] and surgeons. However, failure to recognise the changing epidemiology of the disease, the impact this will have on changing our clinical behaviour, and the need to incorporate this impact into health planning will only make matters worse.
Summary
Abstract
Aim
Method
Results
Conclusion
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Acknowledgements
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Competing Interests
1) New cancer registrations 2019 | Ministry of Health NZ [Internet]. [cited 2022 Sep 12]. Available from: https://www.health.govt.nz/publication/new-cancer-registrations-2019.
2) Gandhi J, Davidson C, Hall C, Pearson J, Eglinton T, Wakeman C, et al. Population-based study demonstrating an increase in colorectal cancer in young patients. Br J Surgery. 2017 Jul 1;104(8):1063-8.
3) Siegel RL, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut [Internet]. 2019;68:2179-85. Available from: http://dx.doi.org/10.1136/gutjnl-2019-319511.
4) Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1) doi:10.1001/ jamasurg.2014.1756. 2015. p. 17-22.
5) te Aho o Te Kahu. He Pūrongo Mate Pukupuku o Aotearoa 2020, The State of Cancer in New Zealand 2020. (revised march 2021) [Internet]. Te Aho o Te Kahu, Cancer control agency. 2021 [cited 2022 Sep 26]. Available from: https://teaho.govt.nz/reports/cancer-state.
6) Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar 1;7(3):262-74.
7) O’Connell JB, Maggard MA, Liu JH, Etzioni DA, Livingston EH, Ko CY. Do Young Colon Cancer Patients Have Worse Outcomes?. 2004; Available from: www.seer.cancer.gov/seerstat.
8) Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer [Internet]. 2016 Mar 15 [cited 2022 Jul 8];122(6):929-34. Available from: https://onlinelibrary-wiley-com.ezproxy.surgeons.org/doi/full/10.1002/cncr.29716.
9) Royal New Zealand College of General Practitioners. Delayed diagnosis of cancer: in perspective. Policy brief. RNZCGP.org. 2015.
10) NCCN guidelines 2022. Treatment by Cancer Type [Internet]. [cited 2022 Sep 13]. Available from: https://www.nccn.org/guidelines/category_1.
11) Scott RB, Rangel LE, Osler TM, Hyman NH. Rectal cancer in patients under the age of 50 years: the delayed diagnosis. Am J Surg [Internet]. 2016 Jun 1 [cited 2021 Sep 2];211(6):1014-8. Available from: http://www.americanjournalofsurgery.com/article/S0002961015005942/fulltext.
12) Blackmore T, Lao C, Chepulis L, Page B, Lawrenson R. The characteristics and outcomes of patients with colorectal cancer in New Zealand, analysed by Cancer Network. N Z Med J. 2020;133(1513):42-52.
13) Kolarich A, George TJ, Hughes SJ, Delitto D, Allegra CJ, et al. Rectal Cancer Patients Younger Than 50 Years Lack a Survival Benefit From NCCN Guideline-Directed Treatment for Stage II and III Disease. Cancer. 2018 Sep 1;124(17):3510-3519. doi: 10.1002/cncr.31527.
14) O’Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, et al. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol and Hepatol. W.B. Saunders; 2021.
15) Kneuertz PJ, Chang GJ, Hu CY, Rodriguez-Bigas MA, Eng C, Vilar ; Eduardo, et al. Overtreatment of Young Adults With Colon Cancer More Intense Treatments With Unmatched Survival Gains. JAMA Surg [Internet]. 2015;150(5):402-9. Available from: https://jamanetwork.com/.
16) Bliggenstorfer JT, Bingmer K, Ofshteyn A, Stein SL, Charles R, Steinhagen E. Neoadjuvant radiation above NCCN guidelines for rectal cancer is associated with age under 50 and early clinical stage. Surg Endosc [Internet]. 2022;36:2925-35. Available from: https://doi.org/10.1007/s00464-021-08585-w.
17) Burnett-Hartman AN, David Powers · J, Chubak J, Corley DA, Ghai NR, Carmit ·, et al. Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network. Cancer Causes & Control [Internet]. 2019 [cited 2022 Sep 13];30:747-55. Available from: https://doi.org/10.1007/s10552-019-01181-3.
18) Downing A, Morris EJAEJA, Richards M, Corner J, Wright P, Sebag-Montefiore D, et al. Health-related quality of life after colorectal cancer in England: A patient-reported outcomes study of individuals 12 to 36 months after diagnosis. J Clin Oncol. 2015 Feb 20;33(6):616-24.
19) Mack JW, Cronin A, Fasciano K, Block SD, Keating NL. Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age. Psychooncology [Internet]. 2016 Sep 1 [cited 2022 Apr 21];1091(September 2015):1085-91. Available from: /pmc/articles/PMC4775442/.
20) de Wind A, Tamminga SJSJ, Bony CAGCAG, Diether M, Ludwig MAM, Velthuis MJMJ, et al. Loss of paid employment up to 4 years after colorectal cancer diagnosis—a nationwide register-based study with a population-based reference group. Cancers (Basel). 2021;13(12):2868.
21) Adams S v., Ceballos R, Newcomb PA. Quality of life and mortality of long-term colorectal cancer survivors in the seattle colorectal cancer family registry. PLoS One. 2016 Jun 1;11(6).
22) Seguin L, Touzani R, Bouhnik ADAD, Charif ABAB, Marino P, Bendiane MKMK, et al. Deterioration of sexual health in cancer survivors five years after diagnosis: Data from the french national prospective vican survey. Cancers (Basel) [Internet]. 2020;12(11):1-21. Available from: www.mdpi.com/journal/cancers.
23) Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. N Engl J Med. 2022 Apr 21;386(16):1547-58.
24) Cercek A, Chatila WK, Yaeger R, Walch H, Fernandes GDS, Krishnan A, etal. A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers. J Natl Cancer Inst. 2021 Aug 18;113(12):1683–92. doi: 10.1093/jnci/djab124. Epub ahead of print. PMID: 34405229; PMCID: PMC8634406.
25) Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol [Internet]. 2019; Available from: https://doi.org/10.1038/.
26) Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017 Feb 2; 12(2):e0171602. doi:10.1371/journal.pone.0171602.
27) Abdullah M, Sukartini Saskia Aziza Nursyirwan Rabbinu Rangga Pribadi Hasan Maulahela Amanda Pitarini Utari Virly Nanda Muzellina Agustinus Wiraatmadja Kaka Renaldi N. Gut Microbiota Profiles in Early- and Late-Onset Colorectal Cancer: A Potential Diagnostic Biomarker in the Future. Digestion [Internet]. 2021;102:823-32. Available from: www.karger.com/dig.
28) Kong C, Liang L, Liu G, Du L, Yang Y, Liu J, et al. Gut microbiota Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer. Gut. 2022;0:1-14.
29) Sandall J, Tribe RM, Avery L, Mola G, Visser GH, Homer CS, et al. Short-term and long-term effects of caesarean section on the health of women and children. The Lancet. 2018 Oct 13;392(10155):1349-57.
30) Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M, et al. Association of Obesity with Risk of Early-Onset Colorectal Cancer among Women. JAMA Oncol. 2019 Jan 1;5(1):37-44.
31) Hur J, Otegbeye E, Joh HK, Nimptsch K, Ng K, Ogino S, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021 Dec 1;70(12):2330-6.
32) Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine [Internet]. 2022 Jul 1 [cited 2022 Aug 31];49:101460. Available from: http://www.thelancet.com/article/S2589537022001900/fulltext.
33) Low EE, Demb J, Liu L, Earles A, Bustamante R, Williams CD, et al. Risk Factors for Early-Onset Colorectal Cancer. Gastroenterol [Internet]. 2020;159(2):492-501.e7. Available from: https://doi.org/10.1053/j.gastro.2020.01.004.
34) Carroll KL, Frugé AD, Heslin MJ, Lipke EA, Greene MW. Diet as a Risk Factor for Early-Onset Colorectal Adenoma and Carcinoma: A Systematic Review. Front Nutr [Internet]. 2022 Jun 9 [cited 2022 Jul 8];9. Available from: https://pubmed.ncbi.nlm.nih.gov/35757246/.
35) Li H, Boakye D, Chen X, Hoffmeister M, Brenner H. Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis. 2021; Available from: http://links.lww.com/AJG/C128,http://links.lww.com/AJG/C129,http://links.lww.com/AJG/C130,http://links.lww.com/AJG/C131AmJGastroenterol2021;116:2173-2183.https://doi.org/10.14309/ajg.0000000000001393.
36) Farver M, smilowitz J. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants Supplementary Issue: Parental Nutritional Metabolism and Health and Disease of Offspring. Nutr Metab Insights [Internet]. 2015(8). Available from: http://www.cdc.gov/breastfeeding/.
37) McDowell R, Perrott S, Murchie P, Cardwell C, Hughes C, Samuel L. Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database. Br J Cancer 2021 126:6 [Internet]. 2021 Dec 17 [cited 2022 Aug 31];126(6):957-67. Available from: https://www.nature.com/articles/s41416-021-01665-7.
38) Hofseth LJ, Hebert JR, Chanda A, Chen H, Love BL, Pena MM, et al. Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol [Internet]. [cited 2022 Apr 12]; Available from: https://doi.org/10.1038/.
39) Thomas RJS, Clarke VA. Community (mis) understanding of colorectal cancer treatment. Aust N Z J Surg [Internet]. 1998 May [cited 2022 Jul 1];68(5):328-30. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1445-2197.1998.tb04764.x.
40) Bowel screening age for Māori and Pasifika lowered - Bowel Cancer NZ [Internet]. [cited 2022 Sep 12]. Available from: https://bowelcancernz.org.nz/new/bowel-screening-age-for-maori-and-pasifika-lowered/.
41) Bowel cancer screening - NHS [Internet]. [cited 2022 Sep 13]. Available from: https://www.nhs.uk/conditions/bowel-cancer-screening/.
42) National Bowel Cancer Screening Program | Australian Government Department of Health and Aged Care [Internet]. [cited 2022 Sep 13]. Available from: https://www.health.gov.au/initiatives-and-programs/national-bowel-cancer-screening-program.
43) Screening for colorectal cancer | Canadian Cancer Society [Internet]. [cited 2022 Sep 13]. Available from: https://cancer.ca/en/cancer-information/cancer-types/colorectal/screening.
44) Niedermaier T, Balavarca Y, Brenner H. Screening for Colorectal Cancer - A German Perspective. Vol. 116, American Journal of Gastroenterology. Wolters Kluwer Health; 2021. p. 841.
45) Knudsen AB, Rutter CM, Peterse EFP, Lietz AP, Seguin CL, Meester RGS, et al. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Colorectal Cancer Screening: An Updated Decision Analysis for the US Preventive Services Task Force [Internet]. 2021 [cited 2022 Sep 13]; (AHRQ Publication No. 20-05271-EF-2). Available from: https://www.ncbi.nlm.nih.gov/books/NBK570833/.
46) Medical Association A. Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement. 2021; Available from: https://jamanetwork.com/.
47) Stamm R, Aluzaite K, Arnold M, Caspritz T, White C, Schultz M. Challenges for the future: the gastroenterology specialist workforce in New Zealand. N Z Med J [Internet]. 2020 [cited 2022 Sep 12];133:1519. Available from: www.nzma.org.nz/journal.
48) A Critical Analysis of the gastroenterology specialist workforce in New Zealand | New Zealand Doctor [Internet]. [cited 2022 Sep 12]. Available from: https://www.nzdoctor.co.nz/article/undoctored/critical-analysis-gastroenterology-specialist-workforce-new-zealand.
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Early-onset colorectal cancer: Never too young
Colorectal cancer (CRC) is the second most common cancer in Aotearoa New Zealand, second only behind prostate cancer in men and breast cancer in woman. It is the second highest cause of cancer death behind lung cancer, with approximately the same death rate as prostate and breast cancer combined.
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