Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

Tu Nguyen-Dumont; Jason A. Steen; Ingrid Winship; Daniel J. Park; Bernard J. Pope; Fleur Hammet; Maryam Mahmoodi; Helen Tsimiklis; Derrick Theys; Mark Clendenning; Graham G. Giles; John L. Hopper; Melissa C. Southey

doi:10.1007/s10689-020-00164-7

Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

Tu Nguyen-Dumont, Jason A. Steen, Ingrid Winship, Daniel J. Park, Bernard J. Pope, Fleur Hammet, Maryam Mahmoodi, Helen Tsimiklis, Derrick Theys, Mark Clendenning, Graham G. Giles, John L. Hopper, Melissa C. Southey

Medicine Monash Health

Research output: Contribution to journal › Article › Research › peer-review

7 Citations (Scopus)

Abstract

The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2) and two in 833 control-families (0.2%, one each of MLH1 and MSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.

Original language	English
Pages (from-to)	197-202
Number of pages	6
Journal	Familial Cancer
Volume	19
Issue number	3
DOIs	https://doi.org/10.1007/s10689-020-00164-7
Publication status	Published - 1 Jun 2020

Keywords

Breast cancer predisposition
DNA mismatch repair
Familial cancer
Gene panel testing
Lynch syndrome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10689-020-00164-7

Cite this

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title = "Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer",

abstract = "The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2) and two in 833 control-families (0.2%, one each of MLH1 and MSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.",

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author = "Tu Nguyen-Dumont and Steen, {Jason A.} and Ingrid Winship and Park, {Daniel J.} and Pope, {Bernard J.} and Fleur Hammet and Maryam Mahmoodi and Helen Tsimiklis and Derrick Theys and Mark Clendenning and Giles, {Graham G.} and Hopper, {John L.} and Southey, {Melissa C.}",

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T1 - Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

AU - Nguyen-Dumont, Tu

AU - Steen, Jason A.

AU - Winship, Ingrid

AU - Park, Daniel J.

AU - Pope, Bernard J.

AU - Hammet, Fleur

AU - Mahmoodi, Maryam

AU - Tsimiklis, Helen

AU - Theys, Derrick

AU - Clendenning, Mark

AU - Giles, Graham G.

AU - Hopper, John L.

AU - Southey, Melissa C.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2) and two in 833 control-families (0.2%, one each of MLH1 and MSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.

AB - The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2) and two in 833 control-families (0.2%, one each of MLH1 and MSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.

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KW - Lynch syndrome

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Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

Abstract

Keywords

UN SDGs

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Other files and links

Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis

Cite this

Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis

Cite this