Role of the 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms in cancer risk modification and treatment.

4th Thursday, 2013  |   Others  |  no comments

Kim YI. Future Oncol. 2009 May;5(4):523-42. doi: 10.2217/fon.09.26. unnamed The role of folate, a water-soluble B vitamin, and single nucleotide polymorphisms (SNPs) in the folate metabolic pathway in human health and disease has been rapidly expanding. Recently, functionally significant SNPs in 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme for intracellular folate homeostasis and metabolism, have been identified and characterized. The MTHFR SNPs are ideal candidates for investigating the role of SNPs in

cancer risk modification and treatment because of their well-defined and highly relevant biochemical effects on intracellular folate composition and one-carbon transfer reactions. Indeed, a large body of molecular epidemiologic evidence suggests that the MTHFR 677 variant T allele is associated with cancer risk in a site-specific manner. Furthermore, biologically plausible mechanisms based on the functional consequences of changes in intracellular folate cofactors resulting from the MTHFR 677T variant exist to readily explain cancer risk modification associated with this variant. In addition, a growing body of in vitro and clinical evidence suggests that the MTHFR SNPs may be an important pharmacogenetic determinant of response to and toxicity of 5-fluorouracil (5FU) and methotrexate (MTX)-based cancer and anti-inflammatory chemotherapy. Furthermore, studies suggest that MTHFR inhibition may be a potential target for increasing chemosensitvity of cancer cells to 5FU-based chemotherapy. Because the MTHFR SNPs are prevalent and MTX and 5FU are widely used for the treatment of common cancers and inflammatory conditions, the pharmacogenetic role of the MTHFR SNPs has significant clinical implications. MTHFR SNPs may play an important role in providing rational, effective and safe tailored treatment to patients with cancer and inflammatory disorders requiring 5FU and MTX-based therapy. As such, largescale human studies and in vitro mechanistic studies are warranted to clarify the pharmacogenetic role of the MTHFR SNPs.

Benign thyroid disease is associated with breast cancer: a meta-analysis.

3rd Wednesday, 2013  |   Breast Cancer  |  no comments

Hardefeldt PJ, Eslick GD, Edirimanne S. Breast Cancer Res Treat. 2012 Jun;133(3):1169-77. doi: 10.1007/s10549-012-2019-3. Epub 2012 Mar 21.



The controversial relationship between benign thyroid diseases and breast cancer (BCa) has been investigated for over 50 years. Despite extensive population studies, the results as a whole have been inconsistent. The purpose of this study was to collate and analyse available data, calculating a pooled odds ratio (OR) of the risk of BC in patients diagnosed with benign thyroid diseases.

Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Inclusion criteria required a confirmed diagnosis of a benign thyroid disease, reporting of an OR or data to calculate an OR (and 95% confidence interval, CI) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled OR calculated. 28 studies were included in the meta-analysis. There was significant evidence of an increased risk of BCa in patients with autoimmune thyroiditis, evident in a pooled OR 2.92 (95% CI 2.13-4.01). In addition, the results supported an increased risk associated with the presence of anti-thyroid antibodies (OR 2.02, 95% CI 1.63-2.50) and goitre (OR 2.26, 95% CI 1.39-3.69). Subgroup analysis of antibody presence revealed increased risk associated with both anti-TPO (OR 2.64, 95% CI 1.82-3.83) and anti-TG (2.71, 95% CI 1.58-4.69).

Quantitative analysis of hypothyroidism and hyperthyroidism was not significant. While these results indicate an association between thyroid auto-immunity and BCa, further prospective studies are required to definitively prove causality.

Where they were honored for this achievement

2nd Tuesday, 2013  |   Uncategorized  |  no comments

(Lionwatcher) 17. Back to back losses to Duke (by 14) and Boston College (by 9) leave me questioning the Golden Domers as a Top Twenty team. Oh well, at 17, nobody at ND is going to be all that impressed. This is well below the national average and speaks highly to the type of care a patient can receive when at Colorado Plains Medical Center,” adds O’Hara. Colorado Plains Medical Center received a Top Rural Hospital distinction and was one of only 21 Rural Top Hospitals recognized across the country. Where they were honored for this achievement..

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WITHDRAWN: Radiotherapy for early breast cancer.

27th Wednesday, 2013  |   Breast Cancer  |  no comments

This Cochrane review of radiation in breast cancer deserves more attention and should be given to women, especially young women, contemplating radiotherapy. The last paragraph says it all; radiotherapy does reduce recurrence and there is benefit for older women in survival rates but there are limits to survival due to hazards in younger women. WITHDRAWN: Radiotherapy for early breast cancer. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD003647. The long-term effects of radiotherapy on mortality from breast cancer and other causes remain uncertain. In this report the Early Breast Cancer Trialists’ Collaborative Group present their systematic overview of treatment with radiotherapy. A meta-analysis was done of 10-year and 20-year results from 40 unconfounded randomised trials of radiotherapy for early breast cancer. Radiotherapy fields generally included not only chest wall (or breast) but also axillary, supraclavicular, and internal mammary nodes. Data collection involved central review of individual patient data on recurrence and cause-specific mortality from 20,000 women.   A reduction of approximately two-thirds in local recurrence was seen in all trials, largely independent of the type of patient or type of radiotherapy (8.8% vs 27.2% local recurrence by year 10). Hence, to assess effects on breast cancer mortality of substantially better local control, results from all trials were combined. Breast cancer mortality was reduced (2p=0.0001) but other, particularly vascular, mortality was increased (2p=0.0003), and overall 20-year survival was 37.1% with radiotherapy versus 35.9% control (2p=0.06). There was little effect on early deaths, but logrank analyses of later deaths indicate that, on average after year 2, radiotherapy reduced annual mortality rates from breast cancer by 13.2% (SE 2.5) but increased those from other causes by 21.2% (SE 5.4). Nodal status, age, and decade of follow-up strongly affected the ratio of breast cancer mortality to other mortality, and hence affected the ratio of absolute benefit to absolute hazard from these proportional changes in mortality.   Radiotherapy regimens able to produce the two-thirds reduction in local recurrence seen in these trials, but without long-term hazard, would be expected to produce an absolute increase in 20-year survival of about 2-4% (except for women at particularly low risk of local recurrence). The average hazard seen in these trials would, however, reduce this 20-year survival benefit in young women and reverse it in older women.   Analysis of cardiac and pulmonary complication probabilities after radiation therapy for patients with early-stage breast cancer. Utehina O, Popovs S, Purina D, et al. Medicina (Kaunas). 2009;45(4):276-85. The purpose of this study was to evaluate the radiobiological implications of clinical use of respiratory-gated techniques for postoperative radiation therapy of early-stage left-sided breast cancer after breast-conserving surgery. Radiation therapy treatment plans of 80 patients with early-stage breast cancer (stage I-II), receiving whole breast irradiation after breast-conserving therapy, were analyzed. The control group consisting of 47 patients received standard radiation therapy, and the respiratory-gated group consisting of 33 patients received deep inspiration-gated radiation therapy. Normal tissue complication probabilities (NTCP) for cardiac mortality and for clinical radiation-induced pneumonitis were calculated for all patients included in present study, using relative seriality model. NTCP data were analyzed for 113 radiation therapy plans, which included free breathing plans for the respiratory-gated groups.   Pneumonitis probability was 0.6% (range 0.0-2.8%) and 0.3% (0.0-1.2%) for control and respiratory-gated group, respectively. Cardiac mortality was 1.3% (0.0-5.0%) and 0.2% (0.0-2.8%) for control and respiratory-gated group, respectively. Using respiratory-gated radiation therapy, NTCP was reduced in comparison with the control group by 83% (P<0.00001) and by 55% (P=0.01270) for cardiac mortality and for clinical radiation-induced pneumonitis, respectively.   Use

of respiratory-gated radiation therapy, for postoperative treatment of early-stage breast cancer, significantly reduces excessive cardiac mortality probability and pulmonary complication probability, as compared to standard radiation therapy techniques. This is especially important from heart complication probability point of view, as cardiac mortality remains one of the important issues of postoperative breast irradiation in patients with early stage breast cancer.

Buy: Fitness gearJanuary is a solid time to sign up for a gym

26th Tuesday, 2013  |   Uncategorized  |  no comments

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