Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis

Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis:

Abstract

Background  

Many properties of cancer cells are reminiscent of those in normal stem cells. Genes important to stem cell development have been significantly implicated in the etiology and clinical outcome of colorectal cancer (CRC). However, the associations of genetic variations in these genes with CRC prognosis have not yet been elucidated.

Methods  

We analyzed the effects of eight potentially functional single nucleotide polymorphisms (SNPs) in six stem cell-related genes on the prognosis of a well-characterized population of 380 Chinese CRC patients diagnosed from February 2006 to January 2010.

Results 

The most significant finding was related to rs879882, a variant in the 5′ region of POU5F1 gene which encodes a protein essential for embryonic stem cell self-renewal and pluripotency, and induced pluripotent stem cell reprogramming. The variant-containing genotypes of rs879882 were associated with an increased risk of recurrence (hazard ratio [HR] = 2.10, 95 % confidence interval [CI] 1.17–3.76, P = 0.01). In chemotherapy-stratified analysis, the association remained borderline significant in patients receiving chemotherapy (HR = 1.97, 95 % CI 0.89–4.34, P = 0.09). In addition, a nonsynonymous SNP of APC gene was also significantly associated with recurrence risk in chemotherapy-treated patients (HR = 2.63, 95 % CI 1.14–6.06 P = 0.02). Further analyses showed a combined effect of the two SNPs in predicting CRC recurrence in patients receiving chemotherapy (P = 0.04) but not in those without chemotherapy (P = 0.43). Moreover, an exploratory multivariate assessment model indicated that these two variants enhanced the power to predict recurrence after chemotherapy.

Conclusion 

We presented one of the first epidemiologic studies showing that stem cell-related genetic variants may impact CRC clinical outcomes, especially in chemotherapy-treated patients.

• Journal Journal of Gastrointestinal Cancer

Stem Cell Network Blog: 35 reasons to like stem cells - images and art/voting open on FB "Cells I See"

Blogger's Note: the FB art/images are fabulous - take a look/vote if you wish

Stem Cell Network Blog: 35 reasons to like stem cells

April 12, 2012

35 reasons to like stem cells

by Lisa Willemse

2010 Cells I See winner: The Beauty of Pluripotency by Kamal Garcha

For the past four years, the Stem Cell Network has held a small image/art contest, known as Cells I See. You may have viewed announcements of the winners in previous blog posts. The contest, by and large, was a quiet affair, known only to a few who weren't part of the Network's annual scientific conference -- where the entries were displayed and conference attendees selected the winner via blind judging.

We were content to keep it this way, until we realized that we were, in essence, hiding some of the most incredible stem cell images we've ever seen. Prompted by interest from the Ontario Science Centre, we installed a small exhibit in their museum and the response was incredible. Most people had no idea what stem cells looked like and were amazed at their beauty and complexity. The overriding message was that people are interested not just in the science of stem cells, but in stem cell images and art.

In response, Cells I See has gone social -- we've opened up the 2012 voting to the world. Anyone with a Facebook profile can participate by "liking" any of the 35 entries in this year's contest. Of course, we invite you to share it with your friends and colleagues as well -- the images are breathtaking, displaying a range of cell types, colours and patterns.
But don't take my word for it, go see them for yourself.

science report: Treating cancer as a chronic disease? (study of clear cell ovarian cancer....)

Treating cancer as a chronic disease?

ScienceDaily (Mar. 29, 2012) — New research from the Technion-Israel Institute of Technology Rappaport Faculty of Medicine and Research Institute and the Rambam Medical Center may lead to the development of new methods for controlling the growth of cancer, and perhaps lead to treatments that will transform cancer from a lethal disease to a chronic, manageable one, similar to AIDS.............

".......For this study, the team took cells from one woman's ovarian clear cell carcinoma and injected them either into or alongside the human stem cell-derived environment. "We noticed very early on, rather strikingly, that the human cancer cells grow more robustly when they are in the teratoma environment compared to any other means in which we grew them, such as in a mouse muscle or under the skin of a mouse," says Skorecki.

The scientists were able to tease out six different kinds of self-renewing cells, based on behavior -- how quickly they grow, how aggressive they are, how they differentiate -- and on their molecular profile. This was a previously unknown finding, that one tumor might have such a diversity of cells with crucial fundamental growth properties. Tzukerman explains that the growth of the cancer cell subpopulations can now be explained by their proximity to the human cell environment.

The researchers cloned and expanded the six distinct cell populations and injected them into the human stem cell teratomas. One key observation is that some cells, which were not self-replicating in any other model, became self-replicating when exposed to the human cells.
Skorecki said that while he wasn't surprised that the human environment affected the growth, he was in fact surprised by the magnitude of the effect: "We've known for years now that cancers are complex organs, but I didn't think the power of the human stem cell environment would be so robust, that it would make such a big difference in how the cells were grown."........

Ovarian Stem Cells Edge Closer to Reality (CME/CE)

Ovarian Stem Cells Edge Closer to Reality (CME/CE)
(MedPage Today) -- Primitive germline stem cells isolated from human ovaries produced oocytes in vitro, supporting the concept that women continue to produce eggs throughout their reproductive years, investigators reported.....

Stem Cells - Medpedia (general discussion)

NCI Cancer Bulletin The Evolving Science of Cancer Stem Cells

".....The CSC concept is “a work in transition,” said Dr. William Matsui, from the Johns Hopkins School of Medicine, whose lab studies the role of stem cells in hematologic cancers. “To me, as a clinical person, the ideal model is one where you can find something that is going to work in humans. We’re far from that.”.."cont'd

full free access: Somatic stem cells of the ovary and their relationship to human ovarian cancers* -- StemBook -- NCBI Bookshelf

define: 'somatic': non-inherited; also refers to all of the cells in the body except the reproductive cells (eg sperm and eggs)

"Mammalian ovaries undergo considerable remodeling during the lifetime of the organism, leading to the supposition that somatic stem cells account for or contribute to this cyclic regeneration. While much of ovarian stem cell research has been focused on germ cells, recent interest in normal somatic stem cells has been driven by their possible links to ovarian cancer stem cells. While evidence for stem cell biology with regards to granulosa cells is scant, recent work has isolated potential somatic stem cells for the theca and ovarian surface epithelium. Additionally, evidence for potential cancer initiating cells for ovarian epithelial carcinomas continues to mount......"

Cancer researchers link ovarian hormone to breast stem cells growth (progesterone)

Note: in research

Residual Cancer Stem Cells after Interval Cytoreductive Surgery following Neoadjuvant Chemotherapy Could Result in Poor Treatment Outcomes for Ovarian Cancer

PMH breast cancer researchers link ovarian hormone to breast stem cells growth

Note: easier to read Medscape article from previous blog post

"Cancer researchers at Princess Margaret Hospital (PMH) have discovered that the ovarian hormone progesterone plays a pivotal role in altering breast stem cells, a finding that has important implications for breast cancer risk.......The findings, published online today in Nature (10.1038/nature09091; http://dx.doi.org/), are significant because reproductive history is among the strongest risk factors for breast cancer, says principal investigator Rama Khokha, a molecular biologist at Ontario Cancer Institute and the Campbell Family Cancer Research Institute, PMH. Other major known risk factors are age, genetics and breast density."

Progesterone induces adult mammary stem cell expansion : Nature

Note: in research; defining the role of progesterones

"Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown..........The emerging role of MaSCs (mammary stem cells) in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse."

full free access: Human Ovarian Cancer Stem Cells -- Bapat, 10.1530/REP-09-0389 -- Reproduction

In research - selected notes:

Stem cells exist in ovarian tumors.