Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers

Daniel J. Park; Kayoko Tao; Florence Le Calvez-Kelm; Tu Nguyen-Dumont; Nivonirina Robinot; Fleur Hammet; Fabrice Odefrey; Helen Tsimiklis; Zhi L. Teo; Louise B. Thingholm; Erin L. Young; Catherine Voegele; Andrew Lonie; Bernard J. Pope; Terrell C. Roane; Russell Bell; Hao Hu; Shankaracharya; Chad D. Huff; Jonathan Ellis; Jun Li; Igor V. Makunin; Esther M. John; Irene L. Andrulis; Mary B. Terry; Mary Daly; Saundra S. Buys; Carrie Snyder; Henry T. Lynch; Peter Devilee; Graham G. Giles; John L. Hopper; Bing Jian Feng; Fabienne Lesueur; Sean V. Tavtigian; Melissa C. Southey; David E. Goldgar

doi:10.1158/2159-8290.CD-14-0212

Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers

Daniel J. Park, Kayoko Tao, Florence Le Calvez-Kelm, Tu Nguyen-Dumont, Nivonirina Robinot, Fleur Hammet, Fabrice Odefrey, Helen Tsimiklis, Zhi L. Teo, Louise B. Thingholm, Erin L. Young, Catherine Voegele, Andrew Lonie, Bernard J. Pope, Terrell C. Roane, Russell Bell, Hao Hu, Shankaracharya, Chad D. Huff, Jonathan EllisJun Li, Igor V. Makunin, Esther M. John, Irene L. Andrulis, Mary B. Terry, Mary Daly, Saundra S. Buys, Carrie Snyder, Henry T. Lynch, Peter Devilee, Graham G. Giles, John L. Hopper, Bing Jian Feng, Fabienne Lesueur, Sean V. Tavtigian, Melissa C. Southey, David E. Goldgar

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

39 Scopus citations

Abstract

Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi- dence interval (CI), 1.29-8.17; P = 0.013]. RINT1 mutation screening of probands from 798 multiplecase breast cancer families identified four additional carriers of rare genetic variants. Analysis of the incidence of first primary cancers in families of women carrying RINT1 mutations estimated that carriers were at increased risk of Lynch syndrome-spectrum cancers [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005], particularly for relatives diagnosed with cancer under the age of 60 years (SIR, 10.9; 95% CI, 4.7-21; P = 0.0003).

Original language	English
Pages (from-to)	804-815
Number of pages	12
Journal	Cancer Discovery
Volume	4
Issue number	7
DOIs	https://doi.org/10.1158/2159-8290.CD-14-0212
State	Published - Jul 2014

Keywords

Breast Neoplasms/genetics
Case-Control Studies
Cell Cycle Proteins/genetics
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
Exome
Female
Genetic Predisposition to Disease
Genetic Variation
High-Throughput Nucleotide Sequencing
Humans
Male
Mutation
Pedigree
Sequence Analysis, DNA

UN SDGs

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

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10.1158/2159-8290.CD-14-0212

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Park, D. J., Tao, K., Le Calvez-Kelm, F., Nguyen-Dumont, T., Robinot, N., Hammet, F., Odefrey, F., Tsimiklis, H., Teo, Z. L., Thingholm, L. B., Young, E. L., Voegele, C., Lonie, A., Pope, B. J., Roane, T. C., Bell, R., Hu, H., Shankaracharya, Huff, C. D., ... Goldgar, D. E. (2014). Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers. Cancer Discovery, 4(7), 804-815. https://doi.org/10.1158/2159-8290.CD-14-0212

@article{40932aadf8a1450494af765c785639fc,

title = "Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers",

abstract = "Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi- dence interval (CI), 1.29-8.17; P = 0.013]. RINT1 mutation screening of probands from 798 multiplecase breast cancer families identified four additional carriers of rare genetic variants. Analysis of the incidence of first primary cancers in families of women carrying RINT1 mutations estimated that carriers were at increased risk of Lynch syndrome-spectrum cancers [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005], particularly for relatives diagnosed with cancer under the age of 60 years (SIR, 10.9; 95% CI, 4.7-21; P = 0.0003).",

keywords = "Breast Neoplasms/genetics, Case-Control Studies, Cell Cycle Proteins/genetics, Colorectal Neoplasms, Hereditary Nonpolyposis/genetics, Exome, Female, Genetic Predisposition to Disease, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Male, Mutation, Pedigree, Sequence Analysis, DNA",

author = "Park, {Daniel J.} and Kayoko Tao and {Le Calvez-Kelm}, Florence and Tu Nguyen-Dumont and Nivonirina Robinot and Fleur Hammet and Fabrice Odefrey and Helen Tsimiklis and Teo, {Zhi L.} and Thingholm, {Louise B.} and Young, {Erin L.} and Catherine Voegele and Andrew Lonie and Pope, {Bernard J.} and Roane, {Terrell C.} and Russell Bell and Hao Hu and Shankaracharya and Huff, {Chad D.} and Jonathan Ellis and Jun Li and Makunin, {Igor V.} and John, {Esther M.} and Andrulis, {Irene L.} and Terry, {Mary B.} and Mary Daly and Buys, {Saundra S.} and Carrie Snyder and Lynch, {Henry T.} and Peter Devilee and Giles, {Graham G.} and Hopper, {John L.} and Feng, {Bing Jian} and Fabienne Lesueur and Tavtigian, {Sean V.} and Southey, {Melissa C.} and Goldgar, {David E.}",

note = "{\textcopyright}2014 American Association for Cancer Research.",

year = "2014",

month = jul,

doi = "10.1158/2159-8290.CD-14-0212",

language = "English",

volume = "4",

pages = "804--815",

journal = "Cancer Discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research Inc.",

number = "7",

}

Park, DJ, Tao, K, Le Calvez-Kelm, F, Nguyen-Dumont, T, Robinot, N, Hammet, F, Odefrey, F, Tsimiklis, H, Teo, ZL, Thingholm, LB, Young, EL, Voegele, C, Lonie, A, Pope, BJ, Roane, TC, Bell, R, Hu, H, Shankaracharya, Huff, CD, Ellis, J, Li, J, Makunin, IV, John, EM, Andrulis, IL, Terry, MB, Daly, M, Buys, SS, Snyder, C, Lynch, HT, Devilee, P, Giles, GG, Hopper, JL, Feng, BJ, Lesueur, F, Tavtigian, SV, Southey, MC & Goldgar, DE 2014, 'Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers', Cancer Discovery, vol. 4, no. 7, pp. 804-815. https://doi.org/10.1158/2159-8290.CD-14-0212

TY - JOUR

T1 - Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers

AU - Park, Daniel J.

AU - Tao, Kayoko

AU - Le Calvez-Kelm, Florence

AU - Nguyen-Dumont, Tu

AU - Robinot, Nivonirina

AU - Hammet, Fleur

AU - Odefrey, Fabrice

AU - Tsimiklis, Helen

AU - Teo, Zhi L.

AU - Thingholm, Louise B.

AU - Young, Erin L.

AU - Voegele, Catherine

AU - Lonie, Andrew

AU - Pope, Bernard J.

AU - Roane, Terrell C.

AU - Bell, Russell

AU - Hu, Hao

AU - Shankaracharya,

AU - Huff, Chad D.

AU - Ellis, Jonathan

AU - Li, Jun

AU - Makunin, Igor V.

AU - John, Esther M.

AU - Andrulis, Irene L.

AU - Terry, Mary B.

AU - Daly, Mary

AU - Buys, Saundra S.

AU - Snyder, Carrie

AU - Lynch, Henry T.

AU - Devilee, Peter

AU - Giles, Graham G.

AU - Hopper, John L.

AU - Feng, Bing Jian

AU - Lesueur, Fabienne

AU - Tavtigian, Sean V.

AU - Southey, Melissa C.

AU - Goldgar, David E.

PY - 2014/7

Y1 - 2014/7

N2 - Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi- dence interval (CI), 1.29-8.17; P = 0.013]. RINT1 mutation screening of probands from 798 multiplecase breast cancer families identified four additional carriers of rare genetic variants. Analysis of the incidence of first primary cancers in families of women carrying RINT1 mutations estimated that carriers were at increased risk of Lynch syndrome-spectrum cancers [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005], particularly for relatives diagnosed with cancer under the age of 60 years (SIR, 10.9; 95% CI, 4.7-21; P = 0.0003).

AB - Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi- dence interval (CI), 1.29-8.17; P = 0.013]. RINT1 mutation screening of probands from 798 multiplecase breast cancer families identified four additional carriers of rare genetic variants. Analysis of the incidence of first primary cancers in families of women carrying RINT1 mutations estimated that carriers were at increased risk of Lynch syndrome-spectrum cancers [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005], particularly for relatives diagnosed with cancer under the age of 60 years (SIR, 10.9; 95% CI, 4.7-21; P = 0.0003).

KW - Breast Neoplasms/genetics

KW - Case-Control Studies

KW - Cell Cycle Proteins/genetics

KW - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics

KW - Exome

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Male

KW - Mutation

KW - Pedigree

KW - Sequence Analysis, DNA

UR - http://www.scopus.com/inward/record.url?scp=84904049854&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-14-0212

DO - 10.1158/2159-8290.CD-14-0212

M3 - Article

C2 - 25050558

AN - SCOPUS:84904049854

SN - 2159-8274

VL - 4

SP - 804

EP - 815

JO - Cancer Discovery

JF - Cancer Discovery

IS - 7

ER -

Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers

Abstract

Keywords

UN SDGs

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