Amanda B Spurdle

..We conducted a population-based, case-control-family study to determine whether androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAGn) was a risk factor for early-onset breast cancer in the Australian population...

..We assessed the association of the prohibitin 3' untranslated region polymorphism with risk of ovarian cancer in the Australian population by case-control comparison...

..96, 95% CI 0.80-1.16; p=0.7), or in subgroups defined by age or family history, or both. Hence, our results do not lend support to the hypothesis that this polymorphism contributes to risk of breast cancer...

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..However, despite its considerable size, our study cannot exclude a small reduced or increased risk associated with the T allele, especially the rare TT genotype...

..The BRCA2 N372H polymorphism appears to be associated with a modest recessively inherited risk of breast cancer in Australian women. This result is consistent with the findings for Northern European women...

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..04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 may increase the risk of ovarian cancer of these histological subtypes specifically. This marginally significant finding will require verification by independent studies...

..Because steroid hormone exposure is known to influence breast cancer risk, we conducted a population-based, case-control-family study to assess the relationship between the CYP17 promoter polymorphism and early-onset breast cancer...

..Our data provide no evidence for an association between ovarian cancer risk and the genotype defined by the AR exon 1 CAG(n) polymorphism, although we cannot exclude small effects, or threshold effects in a small subgroup...

..To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens...

..Women with germline BRCA1 mutations who carry at least one AR allele with 28 or more repeats have been reported to have an earlier age at onset of breast cancer...

..We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case-control study...

..We attempted to replicate the findings of studies assessing such interactions with the -34T-->C polymorphism...

..These results support the need for replication studies to confirm or refute hypothesis-generating studies...

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..We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants...

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..Segregation analysis of 14 kConFab variant-carrying families containing 157 genotyped individuals provided no evidence of segregation with disease. We conclude that the BARD1 Cys557Ser variant is not associated with breast cancer risk...

..We aimed to identify whether KLK10 overexpression could be attributed to genetic variants, in particular, in hormone response elements or transcription factor binding sites...

..BCoR-L1 is located on the X chromosome and is subject to X inactivation...

..Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies...

..Similar approaches may be used to identify genes and underlying genetic risk factors that interact with exogenous stimulants to cause or modify any disease, without a priori knowledge of the pathways involved...

..Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition...

..5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer...

..Arg3052Trp), supporting experimentally derived evidence. These findings highlight the need for improved bioinformatic prediction of splicing aberrations and to refine multifactorial likelihood models used to assess clinical significance...

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..93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women...

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..However, given the marginal significance of these associations and the large number of tests performed, independent replication will be necessary to validate these novel findings...

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..Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease...

..We examined these two ATM mutations in a population-based, case-control series of breast cancer families and multiple-case breast cancer families...

..Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AIB1 glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers...

..However, the magnitude of risk and the subset of variants that are pathogenic for breast cancer remain unresolved...

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..Multifactorial likelihood analysis indicates that the BRCA1 c.135-1G>T and BRCA2 c.7977-1G>C variants are disease-associated mutations which should be managed clinically in the same fashion as classical truncating mutations...

..ORper-allele 1.14 (1.04-1.24) p=0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus...

..Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk with BRCA1/2 mutation status alone...

..Classification of mismatch repair gene variants is assisted by a comprehensive approach that includes in vitro, tumor pathology, clinical, and evolutionary conservation data...

..We hypothesized that germline mutations in FANCD2, BRIP1/BACH1, LMO4 and SFN may account for some of the unexplained multiple-case breast cancer families...

..99-2.18; P = 0.06 for BRCA2). The 95% confidence intervals for per allele risk estimates excluded a twofold risk, indicating that common CDKN1B polymorphisms do not markedly modify breast cancer risk among BRCA1 or BRCA2 carriers...

..We assessed the MnSOD Val9Ala polymorphism and its interaction with dietary antioxidant intake in ovarian cancer risk and survival...

..Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer...

..It is envisaged that the research and clinical application of models developed by ENIGMA will be relevant to the interpretation of sequence variants in other disease genes...

..This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity...

..The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families...

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..98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition...

..In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies...

..We assessed the ability of several assays of LCLs to distinguish carriers of germline BRCA1 and BRCA2 gene mutations from mutation-negative controls to determine their utility for use in a diagnostic setting...

..02). The results of this study, the largest to date, are consistent with a number of previous smaller studies which have also observed that reduced GST function was associated with better survival outcomes in patients with ovarian cancer...

..We sought to evaluate the effect of polymorphisms in the VEGF (Vascular Endothelial Growth Factor) gene on overall survival in ovarian cancer patients...

..Although we identified many novel variants, we found no evidence that highly penetrant germline mutations in these five genes contribute to familial breast cancer susceptibility...

..Five of these neutral variants were also found in at least 1 of 180 healthy controls, suggesting that screening a large number of appropriate controls might be a useful adjunct to other methods for evaluation of unclassified variants...

..Few studies have investigated the role of coding region variation in the RAD51 gene in familial breast cancer, with only one coding region variant--exon 6 c.449G>A (p.R150Q)--reported to date...

..We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes...

..Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer...

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..We therefore analysed the frequency of the functional SNP in 1342 cases and 2256 controls from two breast cancer studies of Caucasian women but found no evidence for an association with breast cancer risk...

..Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant...

..Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema...

..Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival...

..We sought to confirm this association using data from the Australian National Endometrial Cancer Study (ANECS)...

..6 and 4% were observed among cases and controls, respectively. The risk estimate was 0.55 (95%CI 0.24-1.24), suggesting that the RAD52 Y415X polymorphism is not associated with epithelial ovarian cancer in Australian women...

..HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission...

..Our aim was to assess the associations between PCOS, PCOS symptoms, and risk of endometrial cancer in women aged less than 50 years...

..However there is need to be cautious of the noted limitations and caveats of the current model, some of which may be exacerbated by differences in ascertainment and biological pathways to disease for different cancer syndromes...

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..Although predicting the effects of changes in consensus 5' and 3' splice sites near intron:exon boundaries is relatively straightforward, predicting the possible effects of changes in exonic splicing enhancers (ESEs) remains a challenge...

..Although the functional consequences of ABCB1 polymorphisms have been the subject of numerous studies, few have assessed the association with clinical outcome...