jump to navigation

Colon cancer gene expression | Genomic Health January 30, 2008

Posted by ramunas in cancer genetics, colon cancer, genetic testing, sporadic cancer.
3 comments

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.

Advertisements

Technology of a year 2007 January 28, 2008

Posted by ramunas in technology.
add a comment

Yes, it is official. 2007 already was announced as a year of human genome variation. Not surprisingly, the technology of a year 2007 was elected the next generation-sequencing (by Nature Methods).

It is truly remarkable advance not only from a technological perspective, but also it marks the end of ABI monopoly in sequencing.

Congratulations to 454 (Roche), Solexa (Illumina), Solid (ABI) and some more in the frontline (for advances and reviews visit SEQanswers.com).

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.

A New Tumor Markers & Targets January 3, 2008

Posted by ramunas in breast cancer, liver cancer, prostate cancer, pten, research.
3 comments

Yes, there are some already in 2008!

STAT5b – a key regulator of tumorigenesis and mediator of cytokine-growth factor signaling pathway through Janus kinases and signal transducers-activators (JAK/STAT). STAT5b phosphorylation and activation is mediated by several kinases known to be overexpressed in breast cancer, such as epidermal growth factor receptor, HER2, and c-Src. Breast tumor kinase (Brk), also known as protein tyrosine kinase 6, is a nonreceptor tyrosine kinase expressed in more than 60% of breast cancers. STAT5b as well as Brk were established as potential target for breast cancer therapy [ref.] Interestingly, knock-out mouse with defect in this signaling system have dwarfism and are immunodeficient.

Also STAT5 is overexpressed in almost all recurrent prostate cancers that are resistant to hormone therapy and suggest it as a potential drug target in prostate cancer, particularly resistant to other therapies (via).

– NUMB – article in Nature describe a previously unknown function for human NUMB tumour suppressor as a regulator of tumour protein p53. NUMB prevents ubiquitination and degradation of p53 and regulate p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression and NUMB-defective breast tumours display poor prognosis (ref.).

– The EGF (epidermal growth factor) gene 61* G allele polymorphism (SNP) G/G genotype is associated with almost threefold risk for development of hepatocellular carcinoma in liver cirrhosis through modulation of EGF levels (ref.)

– Loss of PTEN expression due to gross mutations is significantly associated with the basal-like cancer (BBC) subtype in human sporadic and BRCA1-associated hereditary breast cancers, article in Nature reports. Interestingly, hereditary mutations in PTEN are responsible for so called rare PTEN-hamartoma tumors syndromes: Cowden syndrome (macrocephaly; skin, intestine, breast and thyroid neoplasias), Bannayan-Riley-Ruvalcaba sydrome, Proteus syndrome, and Proteus-like syndrome.

RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BRCA1/2 mutations carriers – it was associated with earlier onset of breast cancer compared with those individuals with either a BRCA1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002) (ref.)

– Colony stimulating factor-1 (CSF1) circulating levels confer a 33% increased risk of postmenopausal breast cancer and is associated with an 85% reduced risk of premenopausal breast cancer (ref.)

– more?

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 🙂