scholarly journals Review of: The rare ERBB2 variant Ile654Val is associated with an increased familial breast cancer risk

2005 ◽  
Vol 8 (12) ◽  
pp. 1-3
Author(s):  
I. G. Campbell

Citation of original article:B. Frank, K. Hemminki, M. Wirtenberger, J. L. Bermejo, P. Bugert, R. Klaes, R. K. Schmutzler, B. Wappenschmidt, C. R. Bartram, B. Burwinkel. The rare ERBB2 variant lle654Val is associated with an increased familial breast cancer risk. Carcinogenesis 2005; 26: 643–7.Abstract of the original articleOverexpression of the proto-oncogene ERBB2 (HER2/NEU) has been observed in 20–30% of breast cancers involving poor prognosis. Genetic alterations within ERBB2 have been shown to induce carcinogenesis and metastasis. We investigated eight annotated single nucleotide polymorphisms for occurrence in familial breast cancer samples. The confirmed variants Ile654Val, Ile655Val and Ala1170Pro were analysed in subsequent epidemiological studies on familial breast cancer risk. While Ala1170Pro resides within a C-terminally located regulatory domain, the two adjacent polymorphisms Ile654Val and Ile655Val are part of the transmembrane domain. A case–control study analysing a cohort of 348 German familial breast cancer cases and 960 corresponding controls showed no significant association of either Ile655Val (OR = 1.05, 95% CI = 0.82–1.34, P = 0.728) or Ala1170Pro (OR = 0.94, 95% CI = 0.74–1.20, P = 0.632) with familial breast cancer risk. Differences in haplotype frequencies between cases and controls could also not be detected. The ERBB2 variant Ile654Val, however, revealed an increased risk for carriers of the heterozygous Val654 allele (OR = 2.56, 95% CI = 1.08–6.08, P = 0.028). The rare Val654 variant is linked with the more frequent Val655, resulting in two consecutive valine instead of two isoleucine residues within the transmembrane domain. Computational analyses suggest that the Val654–Val655 allele provokes receptor dimerisation and activation, thus stimulating kinase activity and cell transformation. We hypothesise that ERBB2 Val654 represents an oncogenic variant which might, in addition, influence clinical outcome and predict a worse prognosis.

2006 ◽  
Vol 118 (10) ◽  
pp. 2505-2508 ◽  
Author(s):  
Bernd Frank ◽  
Kari Hemminki ◽  
Alfons Meindl ◽  
Barbara Wappenschmidt ◽  
Rüdiger Klaes ◽  
...  

2011 ◽  
Vol 26 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Nupur Mukherjee ◽  
Nilanjana Bhattacharya ◽  
Satyabrata Sinha ◽  
Neyaz Alam ◽  
Runu Chakravarti ◽  
...  

The adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC) genes are key regulatory genes of the Wnt/β-catenin signaling pathway, which are independently involved in maintaining low levels of β-catenin in the cell. In addition to genetic and epigenetic alterations, some genetic polymorphisms in the genes associated with the Wnt signaling pathway have been reported to be associated with an increased risk of cancer, including breast cancer. In the present study we analyzed the association of genotype and haplotype status of two single nucleotide polymorphisms (SNPs), rs2229992 and rs11283943, in the APC and MCC genes, respectively, with an increased risk of breast carcinogenesis in a breast cancer and control population from eastern India. We observed a significant association of the rs11283943 SNP with increased breast cancer risk. Two specific haplotypes involving the minor allele of rs11283943 were found to be associated with an increased breast cancer risk. Kaplan-Meier curves showed a significant association of the 2–2 genotype (genotype homozygous for the rs11283943 minor allele) with decreased survival (p=0.045) of the breast cancer patients in our study, in particular patients with early-onset BC.


2009 ◽  
Vol 121 (3) ◽  
pp. 693-702 ◽  
Author(s):  
Rongxi Yang ◽  
Bettina Schlehe ◽  
Kari Hemminki ◽  
Christian Sutter ◽  
Peter Bugert ◽  
...  

2005 ◽  
Vol 7 (S2) ◽  
Author(s):  
B Frank ◽  
K Hemminki ◽  
M Wirtenberger ◽  
JL Bermejo ◽  
P Bugert ◽  
...  

BMC Cancer ◽  
2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Bernd Frank ◽  
Kari Hemminki ◽  
Alfons Meindl ◽  
Barbara Wappenschmidt ◽  
Christian Sutter ◽  
...  

2009 ◽  
Vol 30 (3) ◽  
pp. 544-545 ◽  
Author(s):  
I. Catucci ◽  
P. Verderio ◽  
S. Pizzamiglio ◽  
S. Manoukian ◽  
B. Peissel ◽  
...  

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 1029-1031 ◽  
Author(s):  
Yussanne P. Ma ◽  
Flora E. van Leeuwen ◽  
Rosie Cooke ◽  
Annegien Broeks ◽  
Victor Enciso-Mora ◽  
...  

Abstract Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.


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