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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Relative frequency and morphology of cancers in STK11 mutation carriers.

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 chi(2) = 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 chi(2) = 1.31; P = 0.25) or between familial and sporadic cases (log-rank chi(2) = 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.[1]

References

  1. Relative frequency and morphology of cancers in STK11 mutation carriers. Lim, W., Olschwang, S., Keller, J.J., Westerman, A.M., Menko, F.H., Boardman, L.A., Scott, R.J., Trimbath, J., Giardiello, F.M., Gruber, S.B., Gille, J.J., Offerhaus, G.J., de Rooij, F.W., Wilson, J.H., Spigelman, A.D., Phillips, R.K., Houlston, R.S. Gastroenterology (2004) [Pubmed]
 
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