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R Eeles

Publications and source records attributed to R Eeles.

At least 37 records · Page 2Linked to original sources

An audit of screening for familial breast cancer before 50 years in the South Thames Region - have we got it right?

We have carried out an audit of breast screening by mammography under 50 years of age in a cohort of 192 women attending family cancer clinics run by the South Thames genetic services. Of these women, six came from families in which a BRCA mutation had been identified, 61 had > 50%, 35 a 20-50% and 90 had < 20% chance of carrying a high risk mutation. In the 192 women in the screened cohort, 9 breast cancers were diagnosed (4.7%), all in high-risk women. Three were diagnosed at the prevalence screen. Three were detected mammographically at subsequent screening rounds; three were detected by breast self-examination (BSE) between screening episodes. One interval cancer was visible on mammogram at presentation but not at screening five months previously. A second cancer was also visible on mammogram at presentation but the normal screening mammogram had been 17 months earlier, outside the recommended interval. The remaining interval cancer was not visible on the mammogram. A total of 363 two-view screening mammograms were performed in the 280 person-years of follow-up; 109 additional investigations were generated: 23 recall mammograms, 18 symptomatic mammograms, 45 ultrasounds, 12 aspiration cytologies and 11 biopsies. Cytology diagnosed malignancy in 1 of 12 cases; breast biopsy in 9 of 11 cases. Twenty-three additional women had ultrasound screening only. This audit suggests that screening below the age 50 years may be unnecessary in families with a low chance of having a BRCA1 or -2 mutation, but it is important to screen high-risk women at least annually and possibly under 35 years.

Adult↗

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: attributes, cancer worry, and barriers to testing in a multicenter clinical cohort.

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.

Adult↗

Healthy women from suspected hereditary breast and ovarian cancer families: the significant others in their lives.

This paper investigates communication and interactions between healthy women from families with a history of breast/ovarian cancer and five statuses of significant others: (1) women friends; (2) sisters; (3) brothers; (4) male partners; and (5) children in order to better understand the way the family deals with cancer genetics risk information and the extent of social support available to its members. We conducted a research ethics committee reviewed exploratory, qualitative study at a major clinical and research cancer centre in the United Kingdom from January to June 2000. Twenty-one semi-structured, in-depth interviews were conducted using a purposive sample of women coming to the cancer genetics risk clinic for the first time, supplemented by 5 months of participant observation. On the whole, women friends consistently provided strong social support. Sisters were usually close, but communication about the breast/ovarian cancer in their family in some cases was quite limited and fraught with emotional overtones. Brothers were the most difficult to relate to regarding cancer in the family and seemed almost to exist in a different 'interrelational space'. The women claimed that their male partners were supportive, but with caveats. Mothers worried about how much information and at what age they should inform their children about the specifics of the family history of breast/ovarian cancer and tried to protect them when they were young. The women were very concerned about their daughters and granddaughters, but were far less concerned about the impact on their sons.

Adult↗

Association between leptin receptor gene polymorphisms and early-onset prostate cancer.

OBJECTIVE: To report a case-control study examining the relationship between polymorphisms in the leptin receptor (OBR) gene and the development of young-onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS: The Lys109Arg (OBR1) and Gln223Arg (OBR2) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS: There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65-2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58-1.26), but neither was statistically significant. CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK.

Adult↗

Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information.

Using data obtained during a retrospective interview study of 30 women who had undergone genetic testing-BRCA1/2 mutation searching-this paper describes how women, previously diagnosed with breast/ovarian cancer, perceive their role in generating genetic information about themselves and their families. It observes that when describing their motivations for undergoing DNA testing and their experiences of disclosing genetic information within the family these women provide care based ethical justifications for their actions. Finally, it argues that generating genetic information and disclosing this information to kin raise different types of ethical issues. The implications of these findings for ethical debates about informed choice in the context of genetic testing are discussed.

Adult↗

Predictive testing for BRCA1/2: attributes, risk perception and management in a multi-centre clinical cohort.

The aim of this multi-centre UK study is to examine the attributes of a cohort offered predictive genetic testing for breast/ovarian cancer predisposition. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. This is the first large multi-centre study of this population in the UK. The study evaluates mental health, perceived risk of developing cancer, preferred risk management options, and motivation for genetic testing. Participants were assessed when coming forward for genetic counselling prior to proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom are female, from nine UK centres participated in the study. There are no gender differences in rates of psychiatric morbidity. Younger women (<50 years) are more worried about developing cancer than older women. Few women provide accurate figures for the population risk of breast (37%) or ovarian (6%) cancer but most think that they are at higher risk of developing breast (88%) and ovarian (69%) cancer than the average woman. Cancer related worry is not associated with perceived risk or uptake of risk management options except breast self-examination. The findings indicate that younger women may be particularly vulnerable at the time of the offer of a predictive genetic test.

Adult↗

Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer.

Epidemiological studies have suggested an association between low selenium levels and the development of prostate cancer. Human cellular glutathione peroxidase I (hGPX1) is a selenium-dependent enzyme that protects against oxidative damage and its peroxidase activity is a plausible mechanism for cancer prevention by selenium. The GPX1 gene has a GCG repeat polymorphism in exon 1, coding for a polyalanine tract of five to seven alanine residues. To test if the GPX1 GCG repeat polymorphism associates with the risk of young-onset prostate cancer we conducted a case-control study. The GPX1Ala genotypes were determined for 267 prostate cancer cases and 260 control individuals using polymerase chain reaction (PCR) amplification with fluorescently labelled primers and an ABI 377 automated genotyper. Associations between specific genotypes and the risk of prostate cancer were examined by logistic regression. We found no significant association between the GPX1 genotypes and prostate cancer. There was however an increased frequency of the GPX1Ala6/Ala6 genotype in the prostate cancer cases compared to controls (OR: 1.67; 95% CI: 0.97-2.87). The result of this study suggests that the GPX1 genotype is unlikely to be associated with the risk of developing prostate cancer.

Adult↗

Genetic testing for women previously diagnosed with breast/ovarian cancer: examining the impact of BRCA1 and BRCA2 mutation searching.

This study sought to investigate the impact of BRCA1 and BRCA2 mutation searching on women previously diagnosed with breast or ovarian cancer. In-depth interviews were undertaken with 30 women who had undergone a BRCA1 and BRCA2 mutation search within the clinical setting. The main reasons reported for undergoing mutation searching were: to provide genetic information for other family members, general altruism, curiosity about the aetiology of cancer, and to provide information to facilitate risk management decisions. In the main, the process of undergoing genetic testing was not experienced as anxiety provoking. The benefit of receiving a result confirming the presence of a genetic mutation was seen as an end to uncertainty, whereas the costs included difficulties in disclosing information to kin and potentially increased anxiety about one's own or others' cancer risks. Women receiving an inconclusive test result reported a range of emotional reactions. There was evidence that some women misunderstood the meaning of this result, interpreting it as definitive confirmation that a cancer-predisposing mutation was not present within the family. It is concluded that women with cancer who participate in BRCA1 and BRCA2 testing need to receive clear information about the meaning and implications of the different types of test results. Some recommendations for clinical practice are discussed.

Adult↗

No germline mutations in CDKN2A (p16) in patients with squamous cell cancer of the head and neck and second primary tumours.

There is increasing evidence that predisposition to some cancers has a genetic component. There is a high incidence of loss of heterozygosity on chromosome 9, in the region of tumour suppressor gene, CDKN2A (also known as p16), in sporadic squamous cell cancer of the head and neck (SCCHN). To investigate the possibility that CDKN2A may be involved in the inherited susceptibility to SCCHN, the 3 coding exons of CDKN2A were sequenced in 40 patients who had developed a second primary cancer after an index squamous cell cancer of the head and neck. No mutations were found and we conclude that CDKN2A mutations do not play a major role in cancer susceptibility in this group.

Aged↗

The incidence of breast cancer from screening women according to predicted family history risk: Does annual clinical examination add to mammography?

In breast cancer, mutations of predisposition genes such as BRCA-1/2 and other genes as yet uncharacterised are manifest in up to 10% of cases. Although the prior probability of the presence of a breast cancer predisposing gene can be calculated for individual women, there is no published evidence to justify predicted risk as a selection criteria for screening. This study aims to define which patient groups with a significant family history should be screened, and whether clinical examination is necessary in addition to mammography. The Claus model was used to predict breast cancer risk in women with a family history. Women were divided into two groups according to their predicted risk: group I consisted of women at standard risk (lifetime risk less than 1:6) and group II with moderate/high risk (lifetime risk greater than or equal to 1:6). Women were cancer-free at the point of entry, and screening consisted of annual clinical examination and mammography from the age of 35 years. This study consisted of 1500 women in group I and 1078 in group II. The period of observation was 5902.0 and 4327.8 women years, respectively. A total of 31 cancers were detected, 12 in group I and 19 in group II. The median age at diagnosis in group II was 45 years (range 26-66 years) compared with 54.5 years (range 38-63 years) in group I (P=0.03). The relative risk of developing breast cancer in group II was 2.6 (95% confidence interval (CI) 1.2-5.8). When compared with breast cancer incidence in the normal population, the standardised incidence ratio in group II was significantly higher at 2.8 (95% CI: 1.7-4.2). The standardised incidence ratio of women in group I was similar to that of the general population (1.1 (95% CI: 0.6-1.8)). A total of 26/31 (84%) cancers detected were palpable, of which 14 (54%) were not visible on mammography. Approximately one-third of all palpable cancers were detected at routine follow-up. Mammography correctly identified 17/31 cancers (55%), but 29% of these were not palpable. Family history screening programmes are effective and women should be selected for screening according to predicted risk. The younger age of diagnosis in group II justifies screening from an earlier age using both annual clinical examination and mammography.

Adult↗

Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer.

There is evidence suggesting that polymorphic variations in the glutathione S-transferases (GSTs) are associated with cancer susceptibility. Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The GSTs have been consistently implicated as cancer susceptibility genes in this context. The GST supergene family includes several loci with well characterized polymorphisms. Approximately 50% of the Caucasian population are homozygous for deletions in GSTM1 and approximately 20% are homozygous for deletions in GSTT1, resulting in conjugation deficiency of mutagenic electrophiles to glutathione. The GSTP1 gene has a polymorphism at codon 105 resulting in an Ile to Val substitution which consequently alters the enzymatic activity of the protein and this has been suggested as a putative high-risk genotype in various cancers. We investigated the relationship between GST polymorphisms and young onset prostate cancer in a case-control study. GSTM1, GSTT1 and GSTP1 genotypes were determined for 275 prostate cancer patients and for 280 geographically matched control subjects. We found no significant difference in the frequency of GSTM1 or GSTT1 null genotypes between cases and controls. GSTP1 genotype was, however, significantly associated with prostate cancer risk: the Ile/Ile homozygotes had the lowest risk and there was a trend in increasing the risk with the number of 105 Val alleles: Ile/Val odds ratio (OR)= 1.30 (95% FCI 0.99-1.69), Val/Val OR = 1.80 (95% FCI 1.11-2.91); Ptrend = 0.026. These results suggest that the GSTP1 polymorphism may be a risk factor for developing young onset prostate cancer. We also found that carrying more than one putative high-risk allele in the carcinogen metabolizing GST family was associated with an elevated risk for early onset prostate cancer (OR 2.48, 95% FCI 1.22-5.04, Ptrend = 0.017).

Adult↗

Hereditary cancer.

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Breast Neoplasms↗

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Antineoplastic Agents, Hormonal↗