2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
for BRCA2 gene . We found 21 different sequence variants in BRCA1
(2 novel) and 36 variants in BRCA2 gene (7 novel) .
We analyzed the distribution and occurrence of sequence variants
in BRCA1 and BRCA2 genes on a healthy population of women in
Croatia in an attempt to distinguish non-tumorigenic from tumorigenic
changes in genomic sequences of BRCA1 and BRCA2 genes . This
may contribute to easier distinction of potentially dangerous from
harmless changes in patients with family history of breast cancer .
P07.020
DNA-repair genetic polymorphisms and breast cancer risk
among cypriot women
M. Loizidou 1 , T. Michael 1 , Y. Marcou 2 , M. Daniel 2 , E. Kakouri 2 , P. Papadopoulos
2 , S. Malas 3 , K. Kyriacou 1 , A. Hadjisavvas 1 ;
1 The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2 Bank of
Cyprus Oncology Centre, Nicosia, Cyprus, 3 Limassol General Hospital, Limassol,
Cyprus.
Breast cancer is the most common malignancy which affects women
worldwide . In an attempt to identify genetic variants which modify
breast cancer risk we are contacting a case-control genetic epidemiology
study using a cohort of 2286 Cypriot women (1109 breast cancer
patients and 1177 age-matched healthy controls) . In the present study
we genotyped 11 single nucleotide polymorphisms (SNPs) in BRCA2,
ERCC2, FANCA, MLH1, MRE11A, MSH2, OGG1, p53, RAD51 and
RAD52 genes which are all involved in the DNA repair pathway . The
prevalence of the 11 SNPs was compared between cases and controls
. Genotype frequencies were compared across groups using the
chi square test and the Mantel-Haenzel test for linear trend . The association
between breast cancer and each SNP was examined using
logistic regression with the SNP genotype tested under models of
complete dominance and recessive inheritance . Three SNPs showed
significant associations with breast cancer. For the most significant
SNPs, the estimated ORs were 0 .74 (95%CI 0 .59-0 .93) and 1 .41
(95%CI 1 .08-1 .83) under a dominant inheritance model, with a combined
Ptrend 0 .0087 and 0 .0076 respectively . These results suggest
that a proportion of the SNPs under study are modifying breast cancer
risk . Large numbers of samples will be needed to verify our results
in other populations . We are currently expanding our analysis to include
a greater number of SNPs and to evaluate potential underlying
gene-gene or gene-environment interactions, in order to advance our
knowledge on the effect of genetic polymorphisms on breast cancer
susceptibility in Cypriot women .
P07.021
Variants in the vitamin D receptor gene and breast cancer
E. Barroso1 , L. P. Fernández1 , R. L. Milne1 , G. Pita1 , P. Zamora2 , J. I. Arias3 , J.
Benítez1 , G. Ribas1 ;
1 2 3 CNIO, Madrid, Spain, La Paz Hospital, Madrid, Spain, Monte Naranco Hospital,
Oviedo, Spain.
Breast cancer is the most commonly occurring cancer among women,
constituting 23% of all cancers . 5-10% of all breast cancers are caused
by germ-line mutations in BRCA1 and BRCA2 . Multiple low-risk genes
with variants common in the general population are thought to produce
a mild susceptibility risk to sporadic breast cancer .
The vitamin D receptor (VDR) gene is a key mediator in the vitamin D
pathway, and has been of long interest in breast cancer aetiology, since
vitamin D exposure has been reported to reduce breast cancer risk . In
the present study we have explored the implication of VDR in sporadic
breast cancer, in the Spanish population since previous studies have
been done in different populations than South European ones .
A total of 576 healthy controls from the Spanish population and 576
consecutive and non-related sporadic breast cancer cases, collected
from different hospitals in Spain, were used in this study . Genotyping
studies were carried out over four SNPs within the VDR gene, located
on exons, in the putative promoter region or in untranslated regions .
Genotyping was performed using TaqMan .
We detected associations for two of the selected SNPs: rs10735810
with OR=1 .49 (95% C .I . 1 .01-2 .21; p=0 .045), and rs731236 with
OR=0 .72 (95% C .I . 0 .51-1 .02; p=0 .064) . We also studied both haplotype
and diplotype using PHASE v2 .0, and detected associations with
disease that were considered with the genotype results . Additionally,
VDR proliferation parameters such as tumor differentiation grade and
tumor aggressiveness will be discussed .
P07.022
mutations in cARD15 and smoking confer susceptibility to
crohn´s disease in the Danish population
A. Ernst1 , I. S. Pedersen1 , H. Okkels1 , M. Ostergaard2 , B. A. Jakobsen1 , N.
Thorsgaard3 , E. Dagiliene1 , V. Andersen2 , A. M. Drewes1 , H. B. Krarup1 ;
1 2 Aalborg Hospital, Aalborg, Denmark, Viborg Hospital, Viborg, Denmark,
3Herning Hospital, Herning, Denmark.
INTRODUCTION: Three mutations in the CAspase Recruitment Domain
gene (CARD15) predispose to Crohn´s disease (CD) in Caucasian
populations .
The frequencies of the three most common CARD15 mutations differ
greatly between ethnic groups . Heterogeneity even exists between the
European countries .
AIMS & METHODS: The aim of this study was to investigate the mutation
frequency in patients with inflammatory bowel disease and healthy
controls in Denmark . Genotyping of the three CARD15 mutations were
performed in 388 patients with Crohn´s disease, 565 patients with ulcerative
colitis and 796 healthy controls using Real-Time PCR . A comparison
of allele and genotype frequencies in the three groups was
made . A possible additive effect of smoking on CARD15 mutations
was also examined .
RESULTS: CARD15 mutations were significantly more common in CD
patients compared with healthy controls (21% vs . 10%; P