Friday, April 17, 2015
Note: study does not discuss Lynch Syndrome
"...These findings rationalize genetic testing for all women with ovarian cancer, which is currently not the standard of care. We need to inform women of the benefits of this option." "
The study "A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population" was co-authored by Moria H. Belanger and Lena Dolman of McGill University; Suzanna L. Arcand of the RI-MUHC; Zhen Shen and George Chong of the Jewish General Hospital; Anne-Marie Mes-Masson and Diane Provencher of Centre de recherche du Centre Hospitalier de l'Université de Montréal and Institut du cancer de Montréal; and Patricia N Tonin of the RI-MUHC and McGill University.
Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer
BACKGROUND:This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer.
METHODS:Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival.
RESULTS:The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016).
CONCLUSIONS:Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.
.....The past several years have seen increasing calls for an ecumenical approach to clinical research, with more flexible standards for what counts as acceptable study designs. Physicians have developed new methods to extract robust analyses from patient registries and from the ever-growing databases provided by electronic medical records. Will this erode the status of RCTs as a gold standard? The rise of personalised medicine, meanwhile, might make it more difficult to defend gold standards in diagnostic and therapeutic practice. Personalised medicine refocuses clinical attention away from the “typical” patients analysed by RCTs and onto the idiosyncrasies, genetic or otherwise, of individual patients. Has the phrase outlived its usefulness in medicine? It is too soon to tell. Yet even as some physicians turn away from their commitment to medical gold standards, some politicians, newly wary about global financial turbulence, talk of restoring the financial gold standard. Gold standards, whether actual or figurative, represent structures of exchange and aspirations toward stability, despite developments that threaten both.