High Cancer Risk in Peutz-Jeghers Syndrome: A Systematic Review and Surveillance Recommendations

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
The American Journal of Gastroenterology (Impact Factor: 10.76). 06/2010; 105(6):1258-64; author reply 1265. DOI: 10.1038/ajg.2009.725
Source: PubMed


Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with increased cancer risk. Surveillance and patient management are, however, hampered by a wide range in cancer risk estimates. We therefore performed a systematic review to assess cancer risks in PJS patients and used these data to develop a surveillance recommendation.
A systematic PubMed search was performed up to February 2009, and all original articles dealing with PJS patients with confirmed cancer diagnoses were included. Data involving cancer frequencies, mean ages at cancer diagnosis, relative risks (RRs), and cumulative risks were collected.
Twenty-one original articles, 20 cohort studies, and one meta-analysis fulfilled the inclusion criteria. The cohort studies showed some overlap in the patient population and included a total of 1,644 patients; 349 of them developed 384 malignancies at an average age of 42 years. The most common malignancy was colorectal cancer, followed by breast, small bowel, gastric, and pancreatic cancers. The reported lifetime risk for any cancer varied between 37 and 93%, with RRs ranging from 9.9 to 18 in comparison with the general population. Age-related cumulative risks were given for any cancer and gastrointestinal, gynecological, colorectal, pancreatic, and lung cancers.
PJS patients are markedly at risk for several malignancies, in particular gastrointestinal cancers and breast cancer. On the basis of these elevated risks, a surveillance recommendation is developed to detect malignancies in an early phase and to remove polyps that may be premalignant and may cause complications, so as to improve the outcome.

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    • "Especially surveillance of the breast, colon and rectum and the small intestines should be established. Different guidelines and recommendations have been suggested through the past decade [8,37,38,45], however, Beggs et al. [8] compared the surveillance programs described in the literature. The authors advocate to postpone the endoscopic screening of the GI-tract until late childhood/early adolescence and suggest that a baseline colonoscopy and upper gastroscopy is performed at age 8 years, or earlier if the patient is symptomatic, and repeated every third year if polyps are detected [8]. "
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    ABSTRACT: Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as Gorlin Syndrome and multiple endocrine neoplasia syndrome 2B are sometimes referred to as HPS. HPS is characterized by the development of hamartomatous polyps in the gastrointestinal tract as well as several extra-intestinal findings such as dermatological and dysmorphic features or extra-intestinal cancer. The syndromes are rare and inherited in an autosomal dominant manner. The diagnosis of HPS has traditionally been based on clinical criteria, but can sometimes be difficult as the severity of symptoms range considerably from only a few symptoms to very severe cases - even within the same family. De novo cases are also frequent. However, because of the discovery of several associated germline-mutations as well as the rapid development in genetics it is now possible to use genetic testing more often in the diagnostic process. Management of the syndromes is different for each syndrome as extra-intestinal symptoms and types of cancers differs. Clinical awareness and early diagnosis of HPS is important, as affected patients and at-risk family members should be offered genetic counselling and surveillance. Surveillance in children with HPS might prevent or detect intestinal or extra-intestinal complications, whereas in adulthood surveillance is recommended due to an increased risk of cancer e.g. intestinal cancer or breast cancer.
    Full-text · Article · Jul 2014 · Orphanet Journal of Rare Diseases
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    • "Peutz-Jeghers syndrome is an autosomal dominantly inherited syndrome characterized by mucocutaneous pigmentation and hamartomatous polyposis [54]. In addition to an elevated risk of gastrointestinal cancers, an increased risk of cancers at other sites, such as breast [55], small bowel, pancreas, ovary, uterus, stomach, cervix, lung, and testis, has been described [56–61]. "
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    ABSTRACT: Breast cancer is the most common malignancy among females. 5%-10% of breast cancer cases are hereditary and are caused by pathogenic mutations in the considered reference BRCA1 and BRCA2 genes. As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1 and BRCA2 predisposition seems to be only a part of the story. These new findings include rare germline mutations in other high penetrant genes, the most important of which include TP53 mutations in Li-Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations in Cowden syndrome. Furthermore, more frequent, but less penetrant, mutations have been identified in families with breast cancer clustering, in moderate or low penetrant genes, such as CHEK2, ATM, PALB2, and BRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.
    Full-text · Article · Mar 2013
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    • "In our PJS patient cohort the cumulative cancer risk of any cancer was nearly 90% by age 65, which is higher than what has been reported recently [1] [4]. The cancer risk was especially elevated in female PJS patients. "
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    ABSTRACT: BACKGROUND: Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome. AIMS: To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation. METHODS: One-hundred and nineteen patients with Peutz-Jeghers syndrome, ascertained in sixteen different Italian centres, were enrolled in a retrospective cohort study. Relative and cumulative cancer risks and genotype-phenotype correlations were evaluated. RESULTS: 36 malignant tumours were found in 31/119 (29 STK11/LKB1 mutation carriers) patients. The mean age at first cancer diagnosis was 41 years. The relative overall cancer risk was 15.1 with a significantly higher risk (p<0.001) in females (22.0) than in males (8.6). Highly increased relative risks were present for gastrointestinal (126.2) and gynaecological cancers (27.7), in particular for pancreatic (139.7) and cervical cancer (55.6). The Kaplan-Meier estimates for overall cumulative cancer risks were 20%, 43%, 71%, and 89%, at age 40, 50, 60 and 65 years, respectively. CONCLUSION: Peutz-Jeghers syndrome entails markedly elevated cancer risks, mainly for pancreatic and cervical cancers. This study provides a helpful reference for improving current surveillance protocols.
    Full-text · Article · Feb 2013 · Digestive and Liver Disease
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