2009 Vienna - European Society of Human Genetics

Cancer genetics
(rs16260) polymorphism have higher frequency in affected cases versus
their healthy related subject. Variation in allelic frequency in this
study in contrast to other population studies, suggests that this SNP
may be a good marker along with other SNPs.
Key words: Gastric cancer, polymorphism, CDH1-160, Iran
P06.036
Gastric and breast cancer occurrence in cDH1 mutated families
L. Huiart 1 , F. Eisinger 1 , V. Bourdon 2 , L. Mansuy 3 , L. Faivre 4 , B. Buecher 5 ,
M. Blayau 6 , O. Caron 7 , J. Flejou 8 , J. Gendre 9 , A. Schielke 10 , A. Sezeur 11 , S.
Olschwang 2 ;
1 Department of Genetic Oncology, INSERM U912(SE4S), IPC, Marseille,
France, 2 Department of Genetic Oncology, IPC, Marseille, France, 3 Department
of Genetic Oncology, CAV, Vandoeuvre-les-Nancy, France, 4 Department of
Genetic, CHU, Dijon, France, 5 Department of Genetic Oncology, HEGP, Paris,
France, 6 Department of Biology, CHU, Rennes, France, 7 Department of Genetic
Oncology, IGR, Villejuif, France, 8 Department of Pathology, AP-HP, Paris,
France, 9 Department of Gastroenterology, AP-HP, Paris, France, 10 Department
of Surgery, Hôpital des Diaconesses, Paris, France, 11 Department of Surgery,
Hôpital des Diaconesses, Paris, France.
Age-dependent penetrance of CDH1 mutations and relevance of clinical
management guidelines are currently debated. Our objective was
therefore to describe variabilities in CDH1-related carcinomas.
Sixteen families were identified with a deleterious CDH1 mutation between
1998 and 2008 in our laboratory. One mutation was found in 4
unrelated families, all others were unique. Fourteen index cases had a
gastric cancer: 9 of diffuse type and 5 unspecified. Ages at diagnosis
ranged from 21 to 63 years (mean = 38). Two index cases were free of
gastric cancer but tested because of a bilateral lobular breast cancer
at age 42 in one case, and a rectal linitis at 23 years of age in the other
case. No family history of gastric cancer was found for 5 mutation carriers.
Associated breast cancer was reported in 3 families (2 cases were
specified as lobular breast cancer). In one family, 6 of 10 mutation
carriers underwent prophylactic gastrectomy; all showed both invasive
and in situ signet cell foci. However the oldest mutation carrier who
declined gastrectomy was clinically asymptomatic at 64 years of age.
In a second family, 13 members were tested for the familial mutation,
and 2 of the 4 mutation carriers were free of cancer at ages 65 and 49
respectively.
The intrafamilial phenotype variability observed in our series indicates
the need for international consortium to provide reliable data on penetrance
of CDH1 mutations before validate guidelines for clinical management.
P06.037
IL-1β -511 T/C polymorphism does not contribute to GEP-NEt
susceptibility
M. Cigrovski Berkovic1 , V. Zjacic-Rotkvic1 , S. Kapitanovic2 ;
1 2 University Hospital “Sestre milosrdnice”, Zagreb, Croatia, Institute Rudjer
Boskovic, Zagreb, Croatia.
GEP-NETs represent a heterogeneous group of tumors, arising from
diffuse endocrine system of gut and pancreas. Tumors are either
solitary, or occur as a part of MEN-1 syndrome. The genetic basis of
GEP-NETs is still largely unknown, but there is growing evidence that
chronic inflammation through proinflammatory cytokines contributes to
patients’ susceptibility to acquire tumors. The role of IL-1β in the gastrointestinal
tract inflammation and cancerosis has been extensively
studied and T allele at -511-IL-1β promotor region was associated with
aggravated inflammatory reaction measured through elevated IL-1β
serum levels, higher gastric cancer susceptibility and worse prognosis.
The aim of our study was to estimate allelic frequency for -511 promotor
SNP in IL-1ß gene in patients with GEP-NETs. DNAs obtained from
101 GEP-NET patients and 150 unrelated healthy volunteers were
genotyped for the IL-1ß -511 SNP using real-time PCR TaqMan ® SNP
genotyping assays. To compare the frequencies χ2 test was used and
results were significant if p