A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

Jon Ambæk Durhuus; Michael Galanakis; Thomas Maltesen; Christina Therkildsen; Susanne Rosthøj; Louise Laurberg Klarskov; Charlotte Kvist Lautrup; Ove Andersen; Mef Christina Nilbert

doi:10.1016/j.tranon.2024.102013

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

Jon Ambæk Durhuus^*, Michael Galanakis, Thomas Maltesen, Christina Therkildsen, Susanne Rosthøj, Louise Laurberg Klarskov, Charlotte Kvist Lautrup, Ove Andersen, Mef Christina Nilbert

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin - Klinisk Genetisk afdeling

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4–2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5–6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1–17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1–1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2–5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8–4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2–37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8–15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.

Originalsprog	Engelsk
Artikelnummer	102013
Tidsskrift	Translational Oncology
Vol/bind	46
ISSN	1944-7124
DOI	https://doi.org/10.1016/j.tranon.2024.102013
Status	Udgivet - aug. 2024

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10.1016/j.tranon.2024.102013Licens: CC BY-NC-ND

Citationsformater

Durhuus, J. A., Galanakis, M., Maltesen, T., Therkildsen, C., Rosthøj, S., Klarskov, L. L., Lautrup, C. K., Andersen, O., & Nilbert, M. C. (2024). A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals. Translational Oncology, 46, Artikel 102013. https://doi.org/10.1016/j.tranon.2024.102013

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title = "A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals",

abstract = "Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4–2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5–6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1–17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1–1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2–5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8–4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2–37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8–15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.",

keywords = "Colorectal cancer, DNA mismatch repair, Immunohistochemistry, Lynch syndrome, Reflex testing",

author = "Durhuus, {Jon Amb{\ae}k} and Michael Galanakis and Thomas Maltesen and Christina Therkildsen and Susanne Rosth{\o}j and Klarskov, {Louise Laurberg} and Lautrup, {Charlotte Kvist} and Ove Andersen and Nilbert, {Mef Christina}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2024",

month = aug,

doi = "10.1016/j.tranon.2024.102013",

language = "English",

volume = "46",

journal = "Translational Oncology",

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Durhuus, JA, Galanakis, M, Maltesen, T, Therkildsen, C, Rosthøj, S, Klarskov, LL, Lautrup, CK, Andersen, O & Nilbert, MC 2024, 'A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals', Translational Oncology, bind 46, 102013. https://doi.org/10.1016/j.tranon.2024.102013

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals. / Durhuus, Jon Ambæk; Galanakis, Michael; Maltesen, Thomas et al.
I: Translational Oncology, Bind 46, 102013, 08.2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

AU - Durhuus, Jon Ambæk

AU - Galanakis, Michael

AU - Maltesen, Thomas

AU - Therkildsen, Christina

AU - Rosthøj, Susanne

AU - Klarskov, Louise Laurberg

AU - Lautrup, Charlotte Kvist

AU - Andersen, Ove

AU - Nilbert, Mef Christina

PY - 2024/8

Y1 - 2024/8

N2 - Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4–2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5–6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1–17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1–1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2–5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8–4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2–37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8–15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.

AB - Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4–2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5–6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1–17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1–1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2–5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8–4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2–37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8–15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.

KW - Colorectal cancer

KW - DNA mismatch repair

KW - Immunohistochemistry

KW - Lynch syndrome

KW - Reflex testing

U2 - 10.1016/j.tranon.2024.102013

DO - 10.1016/j.tranon.2024.102013

M3 - Journal article

C2 - 38824875

AN - SCOPUS:85194922496

SN - 1944-7124

VL - 46

JO - Translational Oncology

JF - Translational Oncology

M1 - 102013

ER -

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

Abstract

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