Elke C Sattler1, Zulfiya Syunyaeva2, Marlene Reithmair3, Wolfram Dempke4, Ortrud K Steinlein5. 1. Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany. 2. Medizinische Klinik und Poliklinik V, German Center for Lung Research, University Hospital, LMU Munich, Munich, Germany. 3. Institute of Human Genetics, University Hospital, LMU Munich, Munich, Germany. 4. Medizinische Klinik und Poliklinik III (Hematology & Oncology), University Hospital, LMU Munich, Munich, Germany. 5. Institute of Human Genetics, University Hospital, LMU Munich, Munich, Germany. Electronic address: Ortrud.Steinlein@med.uni-muenchen.de.
Abstract
OBJECTIVE: Birt-Hogg-Dubé syndrome (BHDS) is an inherited tumour syndrome characterised by three major symptoms: lung cysts with spontaneous pneumothorax, fibrofolliculoma and renal cell cancer. The first family with this syndrome was described in 1975 and one of its members presented with adenomatous colon polyps and colorectal cancer. Since then, it has been a matter of debate whether colorectal cancer is indeed part of the BHDS spectrum and if regular screening should be recommended. DESIGN: We analysed the frequency of colorectal cancer in a large sample of BHDS families. Clinical data were available from 256 BHDS patients (male 130, female 126) belonging to 83 unrelated families. For controls, 83 index patients who attended our outpatient clinic for non-malignancy-related genetic counselling and their family members (total of 519 controls) were used. RESULTS: The patients with BHDS showed a moderately but significantly increased rate of colorectal cancer (5.1% versus 1.5%, p-value .0068). Unexpectedly, 35% of patients with colorectal cancer corresponding to eight of 82 BHDS families fulfilled the revised Bethesda criteria for HNPCC, either because colorectal cancer occurred before age 50 years or because three family members were affected by colorectal cancer. Apart from colorectal cancer, no other HNPCC-associated tumours occurred within the Bethesda criteria-positive families, an observation that argues against a concurrence of BHDS and HNPCC in these families. CONCLUSION: The results suggest that BHDS is associated with early-onset colorectal cancer, a hypothesis that might have a marked impact on preventive screening recommendations.
OBJECTIVE: Birt-Hogg-Dubé syndrome (BHDS) is an inherited tumour syndrome characterised by three major symptoms: lung cysts with spontaneous pneumothorax, fibrofolliculoma and renal cell cancer. The first family with this syndrome was described in 1975 and one of its members presented with adenomatous colon polyps and colorectal cancer. Since then, it has been a matter of debate whether colorectal cancer is indeed part of the BHDS spectrum and if regular screening should be recommended. DESIGN: We analysed the frequency of colorectal cancer in a large sample of BHDS families. Clinical data were available from 256 BHDS patients (male 130, female 126) belonging to 83 unrelated families. For controls, 83 index patients who attended our outpatient clinic for non-malignancy-related genetic counselling and their family members (total of 519 controls) were used. RESULTS: The patients with BHDS showed a moderately but significantly increased rate of colorectal cancer (5.1% versus 1.5%, p-value .0068). Unexpectedly, 35% of patients with colorectal cancer corresponding to eight of 82 BHDS families fulfilled the revised Bethesda criteria for HNPCC, either because colorectal cancer occurred before age 50 years or because three family members were affected by colorectal cancer. Apart from colorectal cancer, no other HNPCC-associated tumours occurred within the Bethesda criteria-positive families, an observation that argues against a concurrence of BHDS and HNPCC in these families. CONCLUSION: The results suggest that BHDS is associated with early-onset colorectal cancer, a hypothesis that might have a marked impact on preventive screening recommendations.
Authors: Mark R Woodford; Avgi Andreou; Masaya Baba; Irma van de Beek; Chiara Di Malta; Iris Glykofridis; Hannah Grimes; Elizabeth P Henske; Othon Iliopoulos; Masatoshi Kurihara; Romain Lazor; W Marston Linehan; Kenki Matsumoto; Stefan J Marciniak; Yukiko Namba; Arnim Pause; Neil Rajan; Anindita Ray; Laura S Schmidt; Wei Shi; Ortrud K Steinlein; Julia Thierauf; Roberto Zoncu; Anna Webb; Mehdi Mollapour Journal: Oncotarget Date: 2022-01-20