IDIBELL Catalan Institute of Oncology

Barcelona, Spain

IDIBELL Catalan Institute of Oncology

Barcelona, Spain
Time filter
Source Type

Eussen S.J.P.M.,University of Bergen | Vollset S.E.,University of Bergen | Vollset S.E.,Norwegian Institute of Public Health | Igland J.,UNIFOB | And 46 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. Methods: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber. Results: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C→T, MTHFR1298A→C, MTR2756A→G, MTRR66A→G, and MTHFD11958G→A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC = 1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC = 0.74 (0.39-1.37); 0.34]. The SLC19A180G→A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01]. Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. ©2010 AACR.

Hoeft B.,German Cancer Research Center | Linseisen J.,German Cancer Research Center | Linseisen J.,Helmholtz Center Munich | Beckmann L.,German Cancer Research Center | And 54 more authors.
Carcinogenesis | Year: 2010

Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r2 cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email:

Rivera B.,Human Genetics Group | Gonzalez S.,IDIBELL Catalan Institute of Oncology | Sanchez-Tome E.,Human Genetics Group | Blanco I.,IDIBELL and FIGTP Catalan Institute of Oncology | And 6 more authors.
Annals of Oncology | Year: 2011

Background: Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. Patients and Methods: We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. Results: APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. Conclusions: Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

PubMed | Civic Mp Arezzo Hospital, Karolinska Institutet, Cancer Research Initiatives Foundation, University of Cologne and 116 more.
Type: | Journal: Nature communications | Year: 2016

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

PubMed | Karolinska Institutet, Danish Cancer Society, University Paris Diderot, IDIBELL Catalan Institute of Oncology and 23 more.
Type: | Journal: International journal of cancer | Year: 2016

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR=0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR=1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR=0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR=1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR=5.66; 95% CI: 1.59, 20.19, p value for interaction<0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms. This article is protected by copyright. All rights reserved.

PubMed | Institute of Oncology, Medical University of South Carolina, University of Cologne, University of Florida and 124 more.
Type: Journal Article | Journal: Nature genetics | Year: 2015

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

PubMed | University of Cologne, Vilnius University, Institute of Human Genetics, Erasmus Medical Center and 110 more.
Type: Journal Article | Journal: PLoS genetics | Year: 2014

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

PubMed | University of Cologne, St George's, University of London, Vilnius University, Institute of Human Genetics and 119 more.
Type: Journal Article | Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | Year: 2015

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

PubMed | University of Cologne, University of Turin, Vilnius University, Erasmus Medical Center and 133 more.
Type: Journal Article | Journal: JAMA | Year: 2015

Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.To identify mutation-specific cancer risks for carriers of BRCA1/2.Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR=1.46; 95% CI, 1.22-1.74; P=210(-6)), c.4328 to c.4945 (BCCR2; RHR=1.34; 95% CI, 1.01-1.78; P=.04), and c. 5261 to c.5563 (BCCR2, RHR=1.38; 95% CI, 1.22-1.55; P=610(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR=0.62 (95% CI, 0.56-0.70; P=910(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR=1.71; 95% CI, 1.06-2.78; P=.03), c.772 to c.1806 (BCCR1; RHR=1.63; 95% CI, 1.10-2.40; P=.01), and c.7394 to c.8904 (BCCR2; RHR=2.31; 95% CI, 1.69-3.16; P=.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR=0.51; 95% CI, 0.44-0.60; P=610(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR=0.57; 95% CI, 0.41-0.80; P=.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Bruni L.,IDIBELL Catalan Institute of Oncology | Diaz M.,IDIBELL Catalan Institute of Oncology | Castellsague X.,IDIBELL Catalan Institute of Oncology | Castellsague X.,CIBER ISCIII | And 4 more authors.
Journal of Infectious Diseases | Year: 2010

Background: Baseline information on human papillomavirus (HPV) prevalence and type distribution is highly desirable to evaluate the impact of prophylactic HPV vaccines in the near future. Methods: A meta-analysis was performed of studies published between 1995 and 2009 that used polymerase chain reaction or Hybrid Capture 2 for HPV detection in women with normal cytological findings. Results: The analysis included 194 studies comprising 1,016,719 women with normal cytological findings. The estimated global HPV prevalence was 11.7% (95% confidence interval, 11.6%-11.7%). Sub-Saharan Africa (24.0%), Eastern Europe (21.4%), and Latin America (16.1%) showed the highest prevalences. Age-specific HPV distribution presented with a first peak at younger ages (<25 years) and, in the Americas and Africa, a rebound at older ages (≥45 years). Among the women with type-specific HPV data (n=215,568), the 5 most common types worldwide were HPV-16 (3.2%), HPV-18 (1.4%), HPV-52 (0.9%), HPV-31 (0.8%), and HPV-58 (0.7%). Conclusions: Although the prevalence of HPV in women with normal cytological findings is high and variable across world regions, HPV types 16, 18, 31, 52, and 58 are consistently found among the 10 most common types in all of them. These results represent the most comprehensive assessment of HPV burden among women with normal cytological findings in the pre-HPV vaccination era worldwide. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Loading IDIBELL Catalan Institute of Oncology collaborators
Loading IDIBELL Catalan Institute of Oncology collaborators