Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis-associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks.

Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes.

Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes.

Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing.

Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2).

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

Objectives: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.

Design: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis).

Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study.

Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).

Patients And Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design).

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).

Selenium as a marker of cancer risk and of selection for control examinations in surveillance.

Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinations in surveillance and as a marker of patients with high risk of cancers.

CHEK2 mutations and the risk of papillary thyroid cancer.

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T).

Methylation of the BRCA1 promoter in peripheral blood DNA is associated with triple-negative and medullary breast cancer.

It has been proposed that methylation signatures in blood-derived DNA may correlate with cancer risk. In this study, we evaluated whether methylation of the promoter region of the BRCA1 gene detectable in DNA from peripheral blood cells is a risk factor for breast cancer, in particular for tumors with pathologic features characteristic for cancers with BRCA1 gene mutations. We conducted a case-control study of 66 breast cancer cases and 36 unaffected controls.

Serum HE4, CA125, YKL-40, bcl-2, cathepsin-L and prediction optimal debulking surgery, response to chemotherapy in ovarian cancer.

Background: The most important prognostic factor in the ovarian cancer is optimal cytoreduction. The neoadjuvant chemotherapy, an only optional method of treatment in this case and is still the subject of debate. The object of this study was to evaluate the usefulness of markers: CA 125, HE4, YKL-40 and bcl-2 as well as cathepsin L in predicting optimal cytoreduction and response to chemotherapy.

Can selenium be a modifier of cancer risk in CHEK2 mutation carriers?

Selenium is an essential trace element for humans, playing an important role in various major metabolic pathways. Selenium helps to protect the body from the poisonous effects of heavy metals and other harmful substances. Medical studies have provided evidence of selenium supplementation in preventing certain cancers.

A low selenium level is associated with lung and laryngeal cancers.

Purpose: It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls.

Methods: We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15).

The risk of gastric cancer in carriers of CHEK2 mutations.

CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T).

Association of MMP8 gene variation with an increased risk of malignant melanoma.

Matrix metalloproteinases (MMPs) are implicated in the development of cancers including malignant melanoma (MM) and breast cancer. We tested the possible association of MMP1 and MMP8 gene variation with these two types of cancer. We genotyped 300 unselected patients with MM, 300 consecutive breast cancer cases, 300 controls for melanoma, and 300 controls for breast cancer (age-matched and sex-matched healthy adults with negative cancer family histories).

CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland.

Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome characterized by a high risk of diffuse stomach cancer and lobular breast cancer. HDGC is caused by germline mutations in the CDH1 gene encoding the E-cadherin which is a member of the transmembrane glycoprotein family responsible for calcium-dependent, cell-to-cell adhesion and plays a fundamental role in the maintenance of cell differentiation and the normal architecture of epithelial tissues. Mutations in the CDH1 gene are detected in 30-46% of families that fulfil strong clinical criteria for HDGC and in about 11% of families fulfilling the modified criteria.

The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers.

Integrins containing the beta(3) subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the beta(3) subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism.

Do BRCA1 modifiers also affect the risk of breast cancer in non-carriers?

We studied whether or not single nucleotide polymorphisms (SNPs), which have been shown to modify the risk of breast cancer in women with a BRCA1 mutation, are associated with cancer risk in unselected (non-hereditary) breast cancer patients. We genotyped seven SNPs in six distinct genes (PHB, RAD51, ITGB3, TGFB1, VEGF, MTHFR) in 1100 unselected Polish breast cancer patients and 1100 controls. The frequencies of genotypes were similar in cases and controls.

Some molecular and clinical aspects of genetic predisposition to malignant melanoma and tumours of various site of origin.

Based on epidemiological data we can assume that at least some malignant melanoma (MM) and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R.