iBlog, iBack, iGene January 7, 2009
Posted by ramunas in cancer genetics, familial cancer, genetic testing, hereditary cancer, personal, research.3 comments
I am back. 2008 were quite important for me – graduated clinical genetics and virtually shifted from traditional-pediatrics based genetics and focused solely to cancer and adult onset disease, also half-sunk in molecular lab – working in best equipped lab with cool people is great. This month will try to handle pyrosequencing and Illumina genotyping, wow.
And defented my long-rolled PhD in tumor cell kinetics and T regulatory cells (enjoy the power of Open Access).
Do you know that 4154delA mutation of BRCA1 gene seems to originated in the Eastern Baltic Sea region of the Northern Europe? Read my and colleagues articles.
Research is the best way to find new health improving strategies. Such example could be CIMBA - “Consortium of Investigators of Modifiers of BRCA1/2″) – an international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers. The goal is to find SNPs which could be important in modifing BRCA mutation effects and thus important in clinic for correct genetic risk stratification. A newly formed Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC) currently is activelly recruiting patients from Lithuania and Latvia for the involvement in CIMBA (contact person for LT – me).
Spare time (hm, a night:) is a good for website developing – www.genetika.lt – is my new website in constant progress in lithuanian language to help translate cancer genetics in understandable manner for patients and doctors. This lovely header is creation of this weekend with the genuine help of Gimp buddy:
Von Hippel-Lindau (VHL) disease – a rare tumor predisposing disorder, where targeted surveillance and early diagnostics is crucial for the improved patients survival – is no longer an “incognito” in my country – developed genetic testing and counseling service will help for these families to get the best from current medical practice. More about VHL.
And for 2009 several new genetic testing are scheduled to come – Familial Adenomatous Polyposis, Multiple Endocrine Neoplasia syndrome (type I and II), Neurofibromatosis type II and Li-Fraumeni syndrome – developing National Hereditary Childhood Cancer Research Platform.
Thats for now – greetings from Vilnius, European Capital of Culture 2009.
Complexity of Breast Cancer August 20, 2008
Posted by ramunas in breast cancer, cancer genetics, familial cancer, genetic testing, hereditary cancer, research.3 comments
This is an exciting time in the study of hereditary factors involved in breast cancer susceptibility. Breast cancer for a long time was classified according histology. Now genetics play a significant role and better knowledge ensures better management and treatment.
Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Only about 30 percent of these cases will be found to be due to a germline mutations in well known BRCA1 and/or BRCA2 genes, but the rest won’t have these mutations. Less than 10 percent of remaining HBC will fall into other rare conditions – and here we can see breast cancer as heterogeneous disease (ref.):
Cowden, Li-Fraumeni syndromes, heterozygosity for Ataxia telangiectasia-mutated gene (ATM) or for CHEK2 1100delC or other rare conditions Nijmegen breakage syndrome (NBS1), familial diffuse gastric cancer (CDH1), Peutz-Jeghers syndrome (STK11), Fanconi anemia (BRIP1, PALB2), Bloom syndrome (BLM)) contribute sligthly – there is consensus for ten most important genes involved in HBC (ref.)
An estimated additional 15–20% of those affected with BC will have one or more first- and ⁄ or second-degree relatives with BC (familial or polygenic breast cancer). Therefore, when these numbers are combined, familial BC risk accounts for approximately 20–25% of the total BC burden (see figure).
Here we’re talking about so called low-penetrance susceptibility genes and variants (SNPs), like rs2981582 in FGFR2, rs889312 in MAP3K1, rs3803662 in TNRC9, rs1801270 in CASP8 and many more, most of which were hot topics in the recent years. Particular alleles (particular “letter” variants of these digitalized “rs” SNPs) only increase risk slightly (twice or so) and are intense study object now, but they sooner or later will enter clinical practice.
(Common) genetic vigilance June 30, 2008
Posted by ramunas in cancer genetics, genetic testing.add a comment
Just wrote some notificaion on commercial tests in my “genetic testing” section:
IMPORTANT NOTE. Some commercial tests for moderate/low cancer risk genetic predisposition are not verified/supported by independent experts or scientific evidence. Please consider these links with common sense and vigilance.
Take care:)
SimpleGenetics(TM) for DNA day April 25, 2008
Posted by ramunas in Simple Genetics, genetic testing, media, personal.2 comments
Happy DNA day! This year in Europe we celebrate it for the first time officially. What a coincidence – yeasterday I’ve received gene T-shirt with mapped 1st chromosome from the magazine Science – wearing it all this day:)
On this occasion I would like to introduce you to SimpleGenetics(TM) genetic test reviews – it could be an independent wiki-based resource dedicated to the provision of reviews and unbiased information about commonly available genetic tests, its clinical validity and utility.
The project aims to improve the quality and accessibility of information regarding genetic tests and help to make informed choice decision for physicians and/or patients.
The information would be reviewed and edited by registered clinicians or scientists working in clinical genetic settings.
There is a preference for objective, scientific evidence-based, comprehensive reviews of clinical evidence and appreciate contribution of both genetic testing companies, clinicians and users to satisfy these goals.
I made this draft in February, and there is some information about Mammaprint available already. Let me know what you think about it and future involvement/contribution/etc. possibility.
Check out at SimpleGenetics.com
Looking to the cancer genetics future | ICG-FBOC meeting February 20, 2008
Posted by ramunas in breast cancer, cancer genetics, familial cancer, genetic testing, hereditary cancer, media, ovarian cancer, personal.add a comment
Next week I’m going to International Collaborative Group on Familial Breast and Ovarian Cancer (ICG-FBOC) meeting (9th symposium) named “Looking to the future cancer diagnostics & treatment: the impact of genetics“ in Cyprus (Κύπρος), Larnaka (Λάρνακα). There is going to be an extensive programme with the presentations of well known researchers from UK (Manchester, London), Norway and Greece. I look really forward to meeting these people and listen to their presentations.
If anyone of my readers are going to be there – please drop me a note – that will be nice to meet you there.
Prostate Cancer | Old&New SNPs and deCODEPrCa February 15, 2008
Posted by ramunas in cancer genetics, familial cancer, genetic testing, hereditary cancer, prostate cancer, research, sporadic cancer.add a comment
This week was undoubtfully very important in elucidation of genetic predisposition to prostate cancer. Three teams (two public and one private) reported their SNP studies in Nature Genetics.
A two-stage genome-wide association study (GWAS), lead by well known Cancer Research UK researchers dr. Rosalind Eeles and Douglas F Easton, was performed on Australian and UK men and confirmed previously associated genetic variants (SNP’s) to prostate cancer at 8q24, occurring in three distinct blocs, which were best “tagged” by SNPs rs6983267, rs1016343 and rs4242384 (as you know, our genome is fragmented and genetic information passes through generations by distinct “blocks” of DNA, called haplotypes, and which can be “marked/tagged” by representative spots, called “tag SNP” – a kind of genetic folksonomy marks) and 17q (a strongest association with rs7501939 (at 17q12) and rs1859962 (at 17q24) . Also several genetic variants on seven new loci on chromosomes 3 (rs2660753), 6 (rs9364554), 7 (rs6465657), 10 (rs10993994), 11 (rs7931342), 19 (rs2735839) and X (rs5945619) were identified, which could explain ~6% of the genetic risk for prostate cancer (a highly significant SNP rs10993994 in MSMB (beta-microseminoprotein) gene proximal promoter constitutes ~2% of risk).
Constantly innovative deCODE based on own results issued predisposition to prostate cancer test deCODE PrCa of 8 SNPs for $500, which is the second commercially available genetic test for prostate cancer after Focus5 test offered by Proactive Genomics. Two new SNP’s single-letter variations (rs721048 on chromosome 2 and rs5945572 on the X chromosome are also included in deCODEme genotyping service, and subscribers can check it out now.
These two SNPs confer relatively modest increases in risk – of approximately 20% and 15% per copy carried, respectively – but because they are also quite common they are each believed to contribute to about 5% of prostate cancer cases (via).
“The genetic testing market is highly competitive. No sooner does one company launch a first-of-its-kind test than another launches a similar one”, Hsien at EyeOnDNA notes about this new test.
Other study also confirms previously reported loci on 8q24 and 17q chromosomes and identifies new SNPs on 7 (rs10486567), 10 (rs10993994; strongest association) and 11 (rs10896449) chromosomes (overal 7 SNPs). Individual population attributable risk (PAR) for prostate cancer for each of the seven independent loci ranged from 8% to 20%.
These findings help clarify genetic structure of prostate cancer, shed light on plausible candidates gene regions and have implications for risk counseling, which can be of clinical importance when cumulative risk is appreciated.
Interestingly, all studies were performed using Illumina bead-chips platform.
Note: to associate any SNP with some condition a strict statistics must be applied: the results must meet or at least approach the “standart of genome-wide significance” with P value <10 minus 7 (0.00000001).
Colon cancer gene expression | Genomic Health January 30, 2008
Posted by ramunas in cancer genetics, colon cancer, genetic testing, sporadic cancer.1 comment so far
The producers (Genomic Health) of breast cancer recurrence 21 gene expression test Oncotype DX (launched in 2004) recently reported the results of two studies, which found genes that could help predict the likelihood of recurrence of and chemotherapy benefit for early-stage colon cancer (via).
Results of the studies were presented January 26, 2008 at ASCO GI, the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium, in Orlando, Florida.
Both study reports used Genomic Health’s quantitative RT-PCR to analyze RNA expression for 375 cancer-related and reference genes from colon tumors of patients who were treated with surgery alone or with surgery and adjuvant 5-fluorouracil/leucovorin (5-FU/LV) chemotherapy (ref.).
In first study (765 + 270 patients) and researchers found 65 genes significantly associated with colon cancer recurrence across – the individual gene expression was associated with an up to 11-fold difference in the risk of disease recurrence (via).
The second study analyzed colon cancers from an additional 508 patients who were treated with surgery plus 5-FU/LV chemotherapy. Fifty six genes were discovered that were significantly associated with disease prognosis for stage II and III colon cancer
Fifteen of the 56 genes were also used as a preliminary model to stratify patients into recurrence-risk categories (via).
Overall, Genomic Health has completed four independent studies involving 1,851 colon cancer patients to evaluate a total of 761 genes. This data will support the selection of the final gene set (ref).
Not long is to wait for the new test (an analog to breast cancer Oncotype DX) to personalize treatment decisions for early-stage colon cancer patients.
Five SNPs Array Predicts Prostate Cancer | Focus5 (TM) January 17, 2008
Posted by ramunas in cancer genetics, familial cancer, genetic testing, hereditary cancer, prostate cancer.3 comments
(source)
Joint Swedish (Karolinska Institute) and US study published in NEJM reveals cummulative association of five (out of 16) previously known genetics variants (SNPs) with prostate cancer – three at 8q24 and one each at 17q12 and 17q24.3 (detailed table and excellent summary from SNPedia).
The idea was simple – it was known that each SNP has only a moderate association and effect wasn’t considered significant enough to justify testing individuals, but when SNPs are combined, the association may be stronger.
The study was carried out in Swedish men (2,893 prostate cancer cases and 1,781 control) and men who had any five or more of these factors associated with prostate cancer plus a family history of prostate cancer (i.e. hereditary/familial cancer), the odds ratio for prostate cancer was 9.46.
In other words, men with five or six of six risk factors, each SNP plus a family history of prostate cancer, were nearly 9.5 times more likely to have the disease.
Also, cumulative effect of these SNPs and family history was independent of PSA results.
Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men studied. It is estimated that almost 90% of the Swedish population carries one or more of the five SNP, and the results should be tested in other populations.
Interestingly, the mechanism by which the analyzed SNPs could affect the risk of prostate cancer is still unknown.
Well, there is already commercial name for this test: Focus5™ Prostate Cancer Risk Test (by fresh Proactive Genomics). [update]
Recently, one of the collaborators group have also identified a variant rs1571801 in DAB2IP gene associated with aggressive prostate cancer.
When Having BRCA Mutation Is Not So Bad or Even Better January 3, 2008
Posted by ramunas in BRCA, breast cancer, genetic testing, hereditary cancer, ovarian cancer.4 comments
There are data accumulating, that having BRCA1/2 mutation from a clinical point of view is not worse that not having it and being affected by breast or ovarian cancer.
There was a study published in 2oo7 summer and discussed, which showed that women mortality from breast cancer is similar for carriers of a BRCA founder mutations and noncarriers (at least in Israeli).
And now, a new 2008 study found, that BRCA1/2 mutation even increases survival in ovarian cancer patients (Ashkenazi)- after 5-years, 46% of the carriers were still alive, compared with 34.4% of the noncarriers. This may be due to distinct clinical behavior and/or to a better response to chemotherapy. (ref.)
I think this is another pros for genetic testing with relaxed criteria (and definitely good news for a BRCA patients), since the main drawback of being BRCA mutation carrier is increased risk for an early breast/ovarian cancer compared with general population, and identifying of high risk patients before the disease strikes could prevent disease and improve survival.
However, I personaly think that present mutations detection fees are overpriced – and I believe that in a very near future there will be a dramatic decrease for all molecular genetic testing prices. A two approaches could be possible, IMHO, (i) a complex (sequencing of all coding regions/whole genome) and (ii) a simple – exploiting already existing technology more effectively and creatively in a cost effective way. I vote for a Simple Genetics 
Happy 2008! | And Briefly About 2007 December 31, 2007
Posted by ramunas in BT Test, DiaGenic, MammaPrint, Oncotype DX, PC Detect, breast cancer, cancer genetics, familial cancer, genetic testing, prostate cancer, sporadic cancer, technology.6 comments
(artwork by Hollis Sigler, 1948-2001)
Happy New Year 2008! Especially to all people, who encountered and battled cancer. Also for those who work to help fight this disease. Lot of advances in our understanding about this condition were achieved this year. It is too naive think that we could completely eliminate cancer, but it is very realistic to think that we can (and will able) to better predict and control this disease.
2007 will be known in history as a breakthrough in understanding of our (Humans: Homo sapiens sapientis) genome variation and enormous success in genome wide association studies (GWAS) for complex disorders ) cancer included (e.g. see my post about breast cancer).
2008 will be definitely an exciting journey through a highway (yet in a desert) of personalized genomics:
(from a movie Electroma, 2007)
I believe that individual molecular profiles will soon help to improve the early detection of cancer : over 50 novel DNA methylation-based biomarkers of breast cancer (by Orion Genomics) can replace mamography in a near future.
(courtesy of Biotage)
Also 37 gene expression markers from peripheral blood (by DiaGenic) will be offered in UK by Opaldia from 2008 (also covered by EyeOnDna, GeneticsAndHealth and MedGadget).
A new BT Test (by Provista Life Sciences) is designed to complement other testing methods to aid doctors in more accurately diagnosing breast cancer in its early stages, when life-saving treatment is most effective (via). The BT Test utilizes a proprietary algorithm to evaluate the levels and relationship of multiple, cancer associated protein biomarkers in blood serum. This data is coupled with a patient’s personal medical profile to generate a comprehensive report designed to assist healthcare providers in making an earlier diagnosis of breast cancer (via).
Two gene-expression assays, Oncotype DX and MammaPrint, have been developed and extensivelly reviewed in 2007, to determine the risk of breast cancer recurrence in patients with stage I or II node-negative breast cancer. In the future, these tests may be useful in determining the need for systemic adjuvant therapy in such patients (ref.).
Unexpectedly, some years ago alterations in mitochondrial DNA – our reminder about The Seven Daughters of Eve – have been suspected to play an important role in the development and progression of cancer. Several mutations have been identified in a wide variety of human tumors, including breast, colorectal, ovarian, gastric, hepatic and esophageal cancers, as well as hematological malignancies [ref.]. Some studies this year points to the importance of the variants in D-loop in familial breast cancer.
Genomic alterations in a new cancer marker – nucleophosmin (NPM1) (by Ipsogen) – has an enormous impact in the biological study, diagnosis, prognostic stratification, and monitoring of minimal residual disease of various lymphomas and leukemias (especially acute myeloid leukemia (AML)). The discovery of NPM1 gene alterations also represents the rationale basis for development of molecular targeted drugs.
Panacea Pharmaceuticals (hm, what a name…) has initiated manufacturing of PC Detectsm kits, the Company’s diagnostic test for prostate cancer, under GMP condition. It based on detection of Human Aspartyl (Asparaginyl) beta-Hydroxylase (HAAH), a cancer biomarker. HAAH has been established as an excellent biomarker for many types of cancer, including prostate cancer. The protein is typically undetectable in sera from cancer-free individuals, thus, an elevated serum protein level of HAAH is highly diagnostic for cancer. PC Detectsm is recommended as an adjunct to the prostate specific antigen (PSA) test and the digital rectal examination (DRE), the currently recommended prostate cancer screening methods (ref.).
A booming field in micro-RNA and cancer field is expected to blossom in forthcoming years – microRNA-10b and breast cancer metastases is a recent example in Nature. It is truly biology’s Big Bang in our 21st century – The RNA revolution.
(photo from Economist)
Tumor immunology, with cancer immunoediting concept in ahead, T regulatory cells and advances in therapeutic cancer vaccines is an important future promise. Individualized cancer immunotherapy with RNA loaded dendritic cells (DC) vaccines (by Argos Therapeutics) is one of the opportunities and new generation of choices.
