A case-control study of Parkinson's disease and tobacco use: gene-tobacco interactions.

A case-control study of genetic, environmental, and occupational risk factors for Parkinson's disease (PD) was carried out in five European countries (Italy, Malta, Romania, Scotland, and Sweden) to explore the possible contribution of interactions among host and environmental factors in sporadic PD. Whereas smoking habits confirmed its negative association with PD, a possible modulatory role of genetic polymorphisms was investigated to obtain further mechanistic insights. We recruited 767 cases of PD and 1989 age-matched and gender-matched controls.

Oral contraceptive use and BRCA penetrance: a case-only study.

Background: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer.

Facial features in children with idiopathic congenital talipes equinovarus.

We assessed whether there is a recognisable pattern of facial morphology in photographs of a series of 62 children with idiopathic congenital talipes equinovarus (CTEV). Photographs were scored for a number of facial characteristics by a research team comprising orthopaedic surgeons and clinical geneticists, to identify a subgroup of children with idiopathic CTEV, who shared characteristic facial features. Seven children were identified as having a "CTEV face".

Probability estimation models for prediction of BRCA1 and BRCA2 mutation carriers: COS compares favourably with other models.

Background: Accurate risk assessment is essential to genetic counselling for a family history of cancer. Several empiric and computer-based risk assessment models have been developed to estimate a counselee's probability of being a carrier of mutation in BRCA1 and/or 2 genes, and to predict the risk of developing breast cancer. The COS model was developed from the better-known BRCAPro model to estimate risk of carriage of BRCA1 or 2 mutation.

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake.

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake.

Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.

Background: Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.

Risk estimation for familial breast cancer: improving the system of counselling.

Women with a family history of breast cancer dominate referrals for cancer genetic risk counselling across Europe. Given limited health care resources, managing this demand, while achieving good value for money for health services, is a major challenge. The paper reports the benefits and associated costs of moving from a traditional system of deriving family history of cancer during the patient's initial clinic attendance, to a protocol-driven system with pre-counselling assessment of family history.

Information recovery in cancer families: value for risk estimations.

Background: Drawing an informative pedigree is fundamental in genetic counselling. It is very common for some parts of pedigrees to remain ambiguous because of the proband's inability to recall the past history of her/his family. Current age, date of birth, date of death and age of diagnosis are the commonest missing information in pedigrees.

Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case-control study in the Grampian region of Scotland.

Cytochrome P-450 CYP1A1 is involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) that are derived from meat intake and tobacco smoking. Expression of the CYP1A1 gene is induced by compounds present in cruciferous vegetables. The glutathione S-transferases play a central role in the detoxification of carcinogens, including PAHs.

Cluster randomized trial of a multifaceted primary care decision-support intervention for inherited breast cancer risk.

Background: GPs are increasingly expected to meet the needs of patients concerned about their risk of inherited breast cancer, but may lack skills or confidence to use complex management guidelines. We developed an evidence-based, multifaceted intervention intended to promote confidence and skills in this area.

Objective: To evaluate the effectiveness of the intervention in improving GP confidence in managing patients concerned about genetic risk of breast cancer.

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype.

Purpose: To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.

Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.

Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.

Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines.

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. In this study high-level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) were created, and comparative genomic hybridisation was used to identify genomic regions associated with resistance to docetaxel.

Assessing patients' participation and quality of decision-making: insights from a study of routine practice in diverse settings.

In the context of a qualitative study exploring patients' participation in decision-making, we investigated how people interpret and respond to structured questions about decision-making about their health care. Seventy-four participants who attended consultations in five clinical areas completed structured measures of decision-making and discussed their responses during interviews. They identified a range of decisions as having being made in their consultations.

Family communication about genetic risk: the little that is known.

Although family communication is important in clinical genetics only a small number of studies have specifically explored the passing on of genetic knowledge to family members. In addition, many of these present exploratory or tentative findings based upon small sample sizes, or data collected only a short time after testing. Nevertheless, if health professionals are to develop effective strategies to help patients' deal with communication issues, we need to know more about what actually happens in families.

Length and somatic mosaicism of CAG and GGN repeats in the androgen receptor gene and the risk of prostate cancer in men with benign prostatic hyperplasia.

Background: The most common malignancy in men worldwide is cancer of the prostate and determinants of prostate cancer (PRCa) risk remain largely unidentified. Many candidate genes may be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. We analysed the polymorphic CAG and GGN repeats sequence in exon 1 of the AR gene to determine if the number of repeats might be an indicator of PRCa risk in patients with BPH.

Vitamin D receptor, HER-2 polymorphisms and risk of prostate cancer in men with benign prostate hyperplasia.

Objective: Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland.

A rapid method of screening for N-acetyltransferase (NAT2) phenotype by use of the WAVE DNA fragment analysis system.

N-Acetyltransferase 2 (NAT2) is involved in Phase II biotransformation of a variety of toxicants. Polymorphisms in the NAT2 gene result in a slow acetylator phenotype, which has been associated with various cancers and neurodegenerative diseases. To date most studies investigating NAT2 genotype/phenotype have adopted an RFLP approach, which is both expensive and time-consuming.

Blood pressure in relation to birth weight in twins and singleton controls matched for gestational age.

Associations between adult blood pressure and birth weight were investigated in 122 same-sex twin pairs aged 18-50 years and 86 singleton controls matched according to maternal age and parity, gender, gestational age, and current age who were recruited via an obstetric database in Aberdeen, Scotland, in 1999. Twins weighed on average 425 g less than controls at birth (p < 0.001) but did not differ significantly in adult height or systolic or diastolic blood pressure from the controls.

Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy.

Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN+).

CYP3A4 promoter variant is associated with prostate cancer risk in men with benign prostate hyperplasia.

Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been linked with PRCa. CYP3A4 may influence PRCa through its role in testosterone metabolism.