Relative frequency and morphology of cancers in STK11 mutation carriers

Wendy Lim, Sylviane Olschwang, Josbert J. Keller, Anne Marie Westerman, Fred H. Menko, Lisa Allyn Boardman, Rodney J. Scott, Jill Trimbath, Francis M. Giardiello, Stephen B. Gruber, Johan J P Gille, G. Johan A Offerhaus, Felix W M De Rooij, J. H Paul Wilson, Allan D. Spigelman, Robin K S Phillips, Richard S. Houlston

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Abstract

Background & Aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank χ2 = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank χ2 = 1.31; P = 0.25) or between familial and sporadic cases (log-rank χ2 = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin-gastroesophageal, small bowel, colorectal, and pancreatic-and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years. Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.

Original languageEnglish (US)
Pages (from-to)1788-1794
Number of pages7
JournalGastroenterology
Volume126
Issue number7
DOIs
StatePublished - Jun 2004

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Protein-Serine-Threonine Kinases
Mutation
Peutz-Jeghers Syndrome
Neoplasms
Germ-Line Mutation
Kaplan-Meier Estimate
Missense Mutation
Pancreatic Neoplasms
Exons
Breast Neoplasms
Incidence

ASJC Scopus subject areas

  • Gastroenterology

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Lim, W., Olschwang, S., Keller, J. J., Westerman, A. M., Menko, F. H., Boardman, L. A., ... Houlston, R. S. (2004). Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology, 126(7), 1788-1794. https://doi.org/10.1053/j.gastro.2004.03.014

Relative frequency and morphology of cancers in STK11 mutation carriers. / Lim, Wendy; Olschwang, Sylviane; Keller, Josbert J.; Westerman, Anne Marie; Menko, Fred H.; Boardman, Lisa Allyn; Scott, Rodney J.; Trimbath, Jill; Giardiello, Francis M.; Gruber, Stephen B.; Gille, Johan J P; Offerhaus, G. Johan A; De Rooij, Felix W M; Wilson, J. H Paul; Spigelman, Allan D.; Phillips, Robin K S; Houlston, Richard S.

In: Gastroenterology, Vol. 126, No. 7, 06.2004, p. 1788-1794.

Research output: Contribution to journalArticle

Lim, W, Olschwang, S, Keller, JJ, Westerman, AM, Menko, FH, Boardman, LA, Scott, RJ, Trimbath, J, Giardiello, FM, Gruber, SB, Gille, JJP, Offerhaus, GJA, De Rooij, FWM, Wilson, JHP, Spigelman, AD, Phillips, RKS & Houlston, RS 2004, 'Relative frequency and morphology of cancers in STK11 mutation carriers', Gastroenterology, vol. 126, no. 7, pp. 1788-1794. https://doi.org/10.1053/j.gastro.2004.03.014
Lim, Wendy ; Olschwang, Sylviane ; Keller, Josbert J. ; Westerman, Anne Marie ; Menko, Fred H. ; Boardman, Lisa Allyn ; Scott, Rodney J. ; Trimbath, Jill ; Giardiello, Francis M. ; Gruber, Stephen B. ; Gille, Johan J P ; Offerhaus, G. Johan A ; De Rooij, Felix W M ; Wilson, J. H Paul ; Spigelman, Allan D. ; Phillips, Robin K S ; Houlston, Richard S. / Relative frequency and morphology of cancers in STK11 mutation carriers. In: Gastroenterology. 2004 ; Vol. 126, No. 7. pp. 1788-1794.
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abstract = "Background & Aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1{\%}, 3{\%}, 19{\%}, 32{\%}, 63{\%}, and 81{\%}, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank χ2 = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank χ2 = 1.31; P = 0.25) or between familial and sporadic cases (log-rank χ2 = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin-gastroesophageal, small bowel, colorectal, and pancreatic-and the risk for these cancers at ages 30, 40, 50, and 60 years was 1{\%}, 10{\%}, 18{\%}, and 42{\%}, respectively. In women, the risk for breast cancer was substantially increased, being 32{\%} by age 60 years. Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.",
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T1 - Relative frequency and morphology of cancers in STK11 mutation carriers

AU - Lim, Wendy

AU - Olschwang, Sylviane

AU - Keller, Josbert J.

AU - Westerman, Anne Marie

AU - Menko, Fred H.

AU - Boardman, Lisa Allyn

AU - Scott, Rodney J.

AU - Trimbath, Jill

AU - Giardiello, Francis M.

AU - Gruber, Stephen B.

AU - Gille, Johan J P

AU - Offerhaus, G. Johan A

AU - De Rooij, Felix W M

AU - Wilson, J. H Paul

AU - Spigelman, Allan D.

AU - Phillips, Robin K S

AU - Houlston, Richard S.

PY - 2004/6

Y1 - 2004/6

N2 - Background & Aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank χ2 = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank χ2 = 1.31; P = 0.25) or between familial and sporadic cases (log-rank χ2 = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin-gastroesophageal, small bowel, colorectal, and pancreatic-and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years. Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.

AB - Background & Aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank χ2 = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank χ2 = 1.31; P = 0.25) or between familial and sporadic cases (log-rank χ2 = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin-gastroesophageal, small bowel, colorectal, and pancreatic-and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years. Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.

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