Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome

W Lim; N Hearle; B Shah; V Murday; S V Hodgson; A Lucassen; D Eccles; I Talbot; K Neale; A G Lim; J O'Donohue; A Donaldson; R C Macdonald; I D Young; M H Robinson; P W R Lee; B J Stoodley; I Tomlinson; D Alderson; A G Holbrook; S Vyas; E T Swarbrick; A A M Lewis; R K S Phillips; R S Houlston

doi:10.1038/sj.bjc.6601030

Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome

W Lim, N Hearle, B Shah, V Murday, S V Hodgson, A Lucassen, D Eccles, I Talbot, K Neale, A G Lim, J O'Donohue, A Donaldson, R C Macdonald, I D Young, M H Robinson, P W R Lee, B J Stoodley, I Tomlinson, D Alderson, A G HolbrookS Vyas, E T Swarbrick, A A M Lewis, R K S Phillips, R S Houlston

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

Abstract / Description of output

Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

Original language	English
Pages (from-to)	308-13
Number of pages	6
Journal	British Journal of Cancer
Volume	89
Issue number	2
DOIs	https://doi.org/10.1038/sj.bjc.6601030
Publication status	Published - 21 Jul 2003

Keywords / Materials (for Non-textual outputs)

Adult
Aged
Breast Neoplasms/genetics
Female
Follow-Up Studies
Gastrointestinal Neoplasms/genetics
Genetic Predisposition to Disease
Genotype
Germ-Line Mutation
Humans
Male
Middle Aged
Peutz-Jeghers Syndrome/complications
Phenotype
Protein-Serine-Threonine Kinases/genetics
Risk Factors

Access to Document

10.1038/sj.bjc.6601030

Cite this

Lim, W., Hearle, N., Shah, B., Murday, V., Hodgson, S. V., Lucassen, A., Eccles, D., Talbot, I., Neale, K., Lim, A. G., O'Donohue, J., Donaldson, A., Macdonald, R. C., Young, I. D., Robinson, M. H., Lee, P. W. R., Stoodley, B. J., Tomlinson, I., Alderson, D., ... Houlston, R. S. (2003). Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. British Journal of Cancer, 89(2), 308-13. https://doi.org/10.1038/sj.bjc.6601030

@article{f8ded085604741b5b6909d0761d79f6c,

title = "Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome",

abstract = "Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.",

keywords = "Adult, Aged, Breast Neoplasms/genetics, Female, Follow-Up Studies, Gastrointestinal Neoplasms/genetics, Genetic Predisposition to Disease, Genotype, Germ-Line Mutation, Humans, Male, Middle Aged, Peutz-Jeghers Syndrome/complications, Phenotype, Protein-Serine-Threonine Kinases/genetics, Risk Factors",

author = "W Lim and N Hearle and B Shah and V Murday and Hodgson, {S V} and A Lucassen and D Eccles and I Talbot and K Neale and Lim, {A G} and J O'Donohue and A Donaldson and Macdonald, {R C} and Young, {I D} and Robinson, {M H} and Lee, {P W R} and Stoodley, {B J} and I Tomlinson and D Alderson and Holbrook, {A G} and S Vyas and Swarbrick, {E T} and Lewis, {A A M} and Phillips, {R K S} and Houlston, {R S}",

year = "2003",

month = jul,

day = "21",

doi = "10.1038/sj.bjc.6601030",

language = "English",

volume = "89",

pages = "308--13",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "2",

}

Lim, W, Hearle, N, Shah, B, Murday, V, Hodgson, SV, Lucassen, A, Eccles, D, Talbot, I, Neale, K, Lim, AG, O'Donohue, J, Donaldson, A, Macdonald, RC, Young, ID, Robinson, MH, Lee, PWR, Stoodley, BJ, Tomlinson, I, Alderson, D, Holbrook, AG, Vyas, S, Swarbrick, ET, Lewis, AAM, Phillips, RKS & Houlston, RS 2003, 'Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome', British Journal of Cancer, vol. 89, no. 2, pp. 308-13. https://doi.org/10.1038/sj.bjc.6601030

TY - JOUR

T1 - Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome

AU - Lim, W

AU - Hearle, N

AU - Shah, B

AU - Murday, V

AU - Hodgson, S V

AU - Lucassen, A

AU - Eccles, D

AU - Talbot, I

AU - Neale, K

AU - Lim, A G

AU - O'Donohue, J

AU - Donaldson, A

AU - Macdonald, R C

AU - Young, I D

AU - Robinson, M H

AU - Lee, P W R

AU - Stoodley, B J

AU - Tomlinson, I

AU - Alderson, D

AU - Holbrook, A G

AU - Vyas, S

AU - Swarbrick, E T

AU - Lewis, A A M

AU - Phillips, R K S

AU - Houlston, R S

PY - 2003/7/21

Y1 - 2003/7/21

N2 - Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

AB - Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

KW - Adult

KW - Aged

KW - Breast Neoplasms/genetics

KW - Female

KW - Follow-Up Studies

KW - Gastrointestinal Neoplasms/genetics

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Germ-Line Mutation

KW - Humans

KW - Male

KW - Middle Aged

KW - Peutz-Jeghers Syndrome/complications

KW - Phenotype

KW - Protein-Serine-Threonine Kinases/genetics

KW - Risk Factors

U2 - 10.1038/sj.bjc.6601030

DO - 10.1038/sj.bjc.6601030

M3 - Article

C2 - 12865922

SN - 0007-0920

VL - 89

SP - 308

EP - 313

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Cite this