Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Abstract

Background: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/ LKB1 (serine/threonine kinase) mutation status are limited. Experimental Design: We analyzed the incidence of cancer in 419 individuals with PeutzJeghers syndrome, and 297 had documented STK11/LKB1 mutations. Results: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis 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%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference m 2 = 0.62; 1 df ; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. Conclusions:The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

A role for LKB1 gene in human cancer beyond the Peutz–Jeghers syndrome

“…However, among the most important associated health-related concerns is the increased risk of cancer development (Giardiello et al, 2000). Gastrointestinal tumors are the most commonly diagnosed malignancies in PJS patients, but the risk of developing cancer from other origins is also significantly higher (Figure 1b) (Giardiello et al, 2000;Hearle et al, 2006a). To some extent, the pattern of tumor susceptibility in PJS patients recapitulates the expression of LKB1 in normal adult and embryonic tissues.…”

“…These differences are puzzling because lung cancer risk is higher but is not among the commonest tumors that occur in PJS. Before ruling out the LKB1 tumor-suppressor role in sporadic tumors other than in lung, the obstacles associated with the detection of mutations in tumors need to be b Stomach a LKB1 PROTEIN EXPRESSION (Luuko et al 1999;Rowan et al 2000Conde et al 2007 (Giardiello et alet al 2000;Lim et al 2004;Hearle et al 2006a) …”

LKB1; linking cell structure and tumor suppression

“…Although there is a possibility that these could transform to become carcinomas, there are several lines of evidence suggesting otherwise and that this aspect of PJS might be functionally separate from the role of LKB1 in suppressing malignant transformation (see below; 'Benign and malignant tumorigenesis'). A markedly increased incidence of carcinomas of the gastrointestinal tract including stomach, small bowel, colon and pancreatic cancer, as well as breast, ovary, uterus, cervix, lung and testis cancer has been observed through longitudinal studies of affected kindreds (Giardiello et al, 1987(Giardiello et al, , 2000Spigelman et al, 1989;Gruber et al, 1998;Lim et al, 2004;Hearle et al, 2006). In addition, rare tumors have been associated with PJS including those of a reproductive origin-including testicular and ovarian sex cord tumors, Sertoli cell tumors and adenoma malignum of the cervix-as well as non-adenocarcinoma pancreatic tumors, including pancreatic intraductal papillary mucinous neoplasia and serous cystadenomas (Podczaski et al, 1991;Young et al, 1995;Tomlinson and Houlston, 1997;Su et al, 1999;Sato et al, 2001;Yee et al, 2003).…”

An Overview of Autosomal Dominant Tumour Syndromes with Prominent Features in the Oral and Maxillofacial Region

“…Peutz-Jeghers syndrome is associated with an increased risk of malignancy in the upper gastrointestinal tract, lower gastrointestinal tract as well at extra-gastrointestinal sites [69,70]. Some large series have shown an increased risk of malignancy in the pancreas, gynecological tract and female Characteristic prominent mucocutaneous pigmentation with a family history of the syndrome 4 a Any number of Peutz-Jeghers polyps and characteristic prominent mucocutaneous pigmentation breast [69][70][71][72].…”

“…Some large series have shown an increased risk of malignancy in the pancreas, gynecological tract and female Characteristic prominent mucocutaneous pigmentation with a family history of the syndrome 4 a Any number of Peutz-Jeghers polyps and characteristic prominent mucocutaneous pigmentation breast [69][70][71][72]. There is also an association with Sertoli cell neoplasia of the testes [73].…”