Pre-clinical data suggest p53-dependent anthracycline-induced apoptosis and p53-independent taxane activity. However, dedicated clinical research has not defined a predictive role for TP53 gene mutations. The aim of the current study was to retrospectively explore the prognosis and predictive values of TP53 somatic mutations in the BIG 02-98 randomized phase III trial in which women with node-positive breast cancer were treated with adjuvant doxorubicin-based chemotherapy with or without docetaxel.

Genome-wide association studies have identified two independent lung cancer susceptibility loci at chromosome 15q25 and one locus at 5p15. We examined the association of genetic variants in these regions with gene expression in lung tumor tissue, in an effort to elucidate carcinogenic mechanisms by which these variants influence lung cancer risk.

The characterization of the whole genome of human papillomavirus type 16 (HPV16) from cervical cancer specimens with multiple infections in comparison with single infection samples as the oncogenic potential of the virus may differ. Cervical carcinoma specimens positive for HPV16 by PCR and INNO-LiPA were randomly selected for whole genome characterization. Two HPV16 single infection and six HPV16 multiple infection specimens were subjected to whole genome analysis by using conserved primers and subsequent sequencing. All HPV16 whole genomes from single infection samples clustered in the European (E) lineage while all multiple infection specimens belonged to the non-European lineage. The variations in nucleotide sequences in E6, E7, E2, L1 and Long control region (LCR) were evaluated. In the E6 region, amino acid changes at L83V were related to increased cancer progression. An amino acid variation N29S within the E7 oncoprotein significantly associated with severity of lesion was also discovered. In all three domains of the E2 gene non synonymous mutations were found. The L1 region showed various mutations which may be related to conformation changes of viral epitopes. Some transcription factor binding sites in the LCR region correlated to virulence were shown on GRE/1, TEF- 1, YY14 and Oct-1. HPV16 European variant prone to single infection may harbor a major variation at L83V which significantly increases the risk for developing cervical carcinoma. HPV16 non-European variants prone to multiple infections may require many polymorphisms to enhance the risk of cervical cancer development.

The aim of this study was to determine the safety and efficacy of metronomic chemotherapy combined with targeted drugs in patients with metastatic breast cancer (MBC). We included 26 untreated patients with HER2-negative (HER-) MBC and poor hormone receptor expression. The analysis of the results suggests that the metronomic chemotherapy combined with bevacizumab and erlotinib is effective and well tolerated.

Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing.

The mechanisms by which trastuzumab imparts clinical benefit remain incompletely understood. Antibody-dependent cellular cytotoxicity via interactions with Fcγ receptors (FcγR) on leukocytes may contribute to its antitumor effects. Single-nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A genes lead to amino acid substitutions at positions 158 and 131, respectively, and affect binding of antibodies to FcγR such that 158V/V and 131H/H bind with highest affinity. This study aimed to determine whether high-affinity SNPs are associated with disease-free survival (DFS) among patients with HER2-positive nonmetastatic breast cancer.

Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated with inactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devised this study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breast cancer progression and development.

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (χ2- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

Identification of low-income women with the rare but serious risk of hereditary cancer and their referral to appropriate services presents an important public health challenge. We report the results of formative research to reach thousands of women for efficient identification of those at high risk and expedient access to free genetic services. External validity is maximized by emphasizing intervention fit with the two end-user organizations who must connect to make this possible. This study phase informed the design of a subsequent randomized controlled trial.

Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen.

Leucovorin, fluorouracil, and oxaliplatin (FOLFOX) is the standard adjuvant therapy for resected stage III colon cancer. Adding cetuximab to FOLFOX benefits patients with metastatic wild-type KRAS but not mutated KRAS colon cancer.

The objective of this study is to evaluate the effectiveness of a self-help coping intervention in reducing intrusive negative thoughts while waiting for cancer genetic risk information.

The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated.

Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women.

Exceptionally high incidence rates of thyroid cancer have been observed in New Caledonia, particularly in Melanesian women, but familial aggregation of thyroid diseases in this population is unknown. We study the association between family history of malignant or benign thyroid diseases and non-medullary thyroid cancer in this country.

Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo.

In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks.

KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include cetuximab or bevacizumab. Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic first-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. The analysis of cetuximab-based and bevacizumab-based regimens in mCRC patients with p.G13D-mutated tumours indicated comparable data for the overall response rate (58 vs. 57%) and progression-free survival (8.0 vs. 8.7 months; hazard ratio: 0.96, P=0.9). Overall survival (OS) was 20.1 months in patients treated with cetuximab-based first-line therapy compared with 14.9 months in patients receiving bevacizumab-containing regimens (hazard ratio: 0.70, P=0.29). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate with a poor outcome (P=0.03). Moreover, a strong trend in favour of capecitabine compared with infusional 5-FU (P=0.06) was observed. Response to treatment correlated with OS in patients receiving cetuximab-based, but not bevacizumab-based regimens. This retrospective pooled analysis suggests comparable efficacy of cetuximab-based and bevacizumab-based first-line therapy in patients with p.G13D mutant mCRC. The combination with capecitabine and irinotecan was associated with a more favourable outcome compared with infusional 5-FU and oxaliplatin.

Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.

To evaluate prognostic and predictive molecular biomarkers in early-stage non-small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy.