Friday, May 06, 2011
FIGO news - Scientists discover three genes linked to breast cancer | International Federation of Gynecology and Obstetrics
Note: the PLOS Genetics paper is technical, references Tamoxifen
"The study, which is published in the journal PloS Genetics, found the genes - C6ORF96, C6ORF97 and C6ORF211 - located next to the oestrogen receptor gene. According to the research, the three genes were linked to the oestrogen receptor but worked separately from it."
"These findings suggest that the genes could contribute to the phenotype associated with oestrogen-receptor positivity. In addition, they may be involved in the mechanism by which genetic variation in this region of the genome contributes to breast cancer susceptibility."
abstract: Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer - Intl Jnl Cancer
Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer.........We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.
full free access: Recent surgical management of ovarian cancer - Journal of Obstetrics and Gynaecology Research
Abstract (also full free access):
Ovarian cancer is the second most common gynecological malignancy in the USA, and the majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease. The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy. As the evidence has accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction has evolved, the surgical techniques have expanded in order to achieve this goal. This article discusses the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge.
Ovarian cancer affects 1 in 70 women, being the second most common gynecological malignancy in the USA. The majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease.1 The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy.2 As the evidence accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction evolved, the surgical techniques expanded in order to achieve this goal.
Regardless of the debate on whether it is the biology of the tumor rather than the surgical effort that allows optimal cytoreduction,3,4 and regardless of whether the patient has already received a course of neoadjuvant chemotherapy,5 once the decision to proceed with surgery is taken, its goal should be to achieve maximal cytoreduction.
This article will review the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge. The data reviewed pertain mainly to high-grade serous carcinoma. Discussing the role of primary versus interval debulking is beyond the scope of this article and will not be reviewed here.
abstract: The effect of estrogen vs. combined estrogen-progestogen therapy on the risk of colorectal cancer
"While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk."
abstract: Pregnancy after adolescent and adult cancer: A population-based matched cohort study (Norway)
"In summary, fertility-preserving attempts have succeeded in patients with ovarian or testicular cancer and in males with Hodgkin lymphoma. Male survivors initiated pregnancies in a higher degree than female survivors."
abstract: Association of low-risk MSH3 and MSH2 variant alleles with Lynch syndrome: Probability of synergistic effects - Intl Jnl of Cancer
"These variants were identified through denaturing high performance liquid chromatography and subsequent DNA sequencing. In one Lynch family, the index case with early-onset colon cancer was a carrier of a polymorphism in the MSH2 gene and two variants in the MSH3 gene. These variants were associated with the disease in the family, thus suggesting the involvement of MSH3 in colon tumour progression. We hypothesise a model in which variants of the MSH3 gene behave as low-risk alleles that contribute to the risk of colon cancer in Lynch families, mostly with other low-risk alleles of MMR genes."
Evaluation of predictive models for the identification in daily practice of patients with lynch syndrome - Intl Jnl of Cancer
"....Both approaches failed to identify two of the eight mutation carriers (the same two patients, aged 67 and 81 years, both with no family history). Thus, like the revised Bethesda guidelines, predictive models did not identify all Lynch syndrome patients in our series of unselected CRC. Our results support systematic screening for MMR deficiency in all new CRC cases."
Note: comments in brackets/italicized are blogger's comments; worthwhile reading with several key points of interest such as:
"It should be noted that stage II disease is the least commonly diagnosed stage of ovarian cancer. This is likely because there is no anatomic boundary between the pelvis and upper abdomen. If disease has spread outside of the ovary to pelvic structures, it is also likely to spread to the upper abdomen. In the past, trials of the Gynecologic Oncology Group (GOG) have combined stages I and II as a definition of “early” ovarian cancer, with stages III and IV designated as “advanced” ovarian cancer. However, given the observed higher recurrence rate seen for stage II disease, the GOG is now including stage II in the category of advanced disease for trial purposes."
"Studies (note: over decades) have documented that almost one-third (note: an average) of apparent early stage patients will have more advanced stage disease when full staging is done. In contrast, chemotherapy improves progression-free survival (PFS) for patients with stage IA or IB poorly differentiated disease, stage IC, or stage II disease, and these patients should receive adjuvant chemotherapy."
"There is a clear need for additional clinical trials to assess whether the clinical benefits such as quality of life, symptom control, and survival advantages outweigh the added exposure to the side effects of the agents or treatments used in the maintenance or consolidation setting."
Best way to screen for Lynch syndrome in women with endometrial cancer identified - - ModernMedicine (U of B.C./BCCA)
"Because endometrial (uterine) cancers associated with Lynch syndrome most likely present at an earlier age than colorectal cancer -- which is also commonly associated with the syndrome -- screening in these women could provide benefit and help extend overall life expectancy.
Testing all women with endometrial cancer would carry substantial costs, so researchers led by Dr. Janice Kwon, of the University of British Columbia and the British Columbia Cancer Agency in Vancouver, performed a cost-benefit analysis to determine the ideal screening criteria."...
".. The decreases (in deaths) for ovary, lung, and cervical cancers were limited to the most recent 5-year period."
PLoS Medicine: Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview
Note: PLOS Medicine is an open-text publisher (free full access), below are a couple of excerpts of interest
BackgroundThere is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies.
Discussion Top"............The increased risk in adverse effects in some studies was not consistently related to any particular study design—RCTs found a significant risk of adverse effects associated with the intervention under investigation in eight instances, while observational studies showed a significantly elevated risk in 11 cases.
............Although reasons for discrepancies are unclear, specific factors which may have led to differences in adverse effect estimates were discussed by the respective authors.................
..........While there are a few instances of sizeable discrepancies, the pooled estimates in Figure 2 and Table 2 indicate that in the scheme of things (particularly where larger, more precise primary studies are available), meta-analysis of observational studies yield adverse effects estimates that broadly match those from meta-analysis of RCTs..........."