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P Pharoah

Publications and source records attributed to P Pharoah.

18 recordsLinked to original sources
PubMed2003

Issues of consent and feedback in a genetic epidemiological study of women with breast cancer.

Women (N=21) who had had breast cancer and had been enrolled in a large genetic breast cancer epidemiological study were interviewed about their experience of participation in the study, their attitudes to the confidentiality of data, and the feedback of personal and general research results. Collection of family history information seemed more salient in indicating the genetic nature of the study than the enrolment information sheet. There were no concerns about confidentiality. While participants would have welcomed general feedback about the results of the study and were critical that this had not been provided, the feedback of personal information proved complicated and, sometimes, difficult. It is suggested that individual feedback of genetic test information in epidemiological studies should be undertaken only when there are specific reasons.

Adult↗
PubMed2001

Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma.

BACKGROUND & AIMS: Interleukin (IL)-1 gene cluster proinflammatory polymorphisms have been associated with development of gastric atrophy and with increased risk of gastric carcinoma. We aimed to determine the association between IL-1 loci polymorphisms and increased risk of gastric carcinoma in samples from a Portuguese population, and to find whether there was any relationship with the histologic types of gastric carcinoma. METHODS: In a case-control study including 220 controls and 152 patients with gastric carcinoma (intestinal, 76; diffuse, 37; and atypical, 39), both the IL-1B-511 biallelic polymorphism and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. RESULTS: We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma. A trend towards an increased risk of tumor development was also observed in patients with diffuse-type gastric carcinoma. No significant relationship was observed in patients with atypical carcinoma. Carriers of IL-1B-511T and IL-1RN*2 homozygotes had increased risk for developing intestinal-type gastric carcinoma with odds ratios of 2.7 (95% confidence interval [CI], 1.5-4.9) and 3.1 (95% CI, 1.5-6.5), respectively. Statistical analysis showed an interaction between the 2 loci with the risk conferred by the IL-1B-511T allele substantially increased (odds ratio, 9.0; 95% CI, 3.5-23.0) in individuals homozygous for the IL-1RN*2 allele. CONCLUSIONS: Our results provide further support to the association between IL-1 gene cluster proinflammatory polymorphisms and increased risk of gastric carcinoma. Furthermore, we found evidence pointing to the existence of a synergistic interaction between the IL-1B and IL-1RN polymorphisms.

Adult↗
PubMed2000

The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was < or = 67 years at diagnosis. No germ-line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (< or = 56 years) and who were members of an affected sibling pair. One is a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate cancer at 56 years. In both cases, the wild-type allele was lost in the patient's prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.

Adult↗
PubMed2000

Hospital outbreak of Salmonella virchow possibly associated with a food handler.

A foodborne outbreak of salmonella infection at a private hospital in London in 1994 was found to be associated with eating turkey sandwiches prepared by a food handler. One patient, nine staff, and a foodhandler's baby were confirmed to have Salmonella enterica serotype virchow, phage type 26 infection. The attack rate was estimated to be 5% among the approximately 200 patients and staff at risk. A food handler reportedly became ill days after, but her baby days before, the first hospital case. Although it appeared to be a single outbreak, antibiogram analysis, supplemented by plasmid profile typing, demonstrated that there were two strains of S. virchow involved, one with resistance to sulphonamides and trimethoprim and a second sensitive to these antimicrobial drugs. Mother and child had different strains. The investigation demonstrated the importance of full phenotypic characterization of putative outbreak strains including antimicrobial susceptibility testing. Outbreaks of foodborne infection in hospitals are preventable and are associated with high attack rates and disruption of services. There is a need for good infection control policies and training of all staff involved in patient care as well as in catering services. Consultants in Communicable Disease (CCDCs) should include private hospitals in their outbreak control plans. Good working relations between Infection Control Doctors (ICDs) in the private health sector and their local CCDCs are important if outbreaks are to be properly investigated.

Adult↗
PubMed2000

Comparative trends in cause-specific fetal and neonatal mortality in twin and singleton births in the North of England, 1982-1994.

OBJECTIVE: To examine trends in cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. DESIGN: Descriptive analysis based on a regional register. SETTING: The Northern Health Region of England, 1982-1994. SAMPLE: Two hundred and thirty-six fetal and 356 neonatal twin deaths; 2,687 fetal and 2,301 neonatal singleton deaths from a population of 10,734 twins and 505,477 singletons. MAIN OUTCOME MEASURES: Fetal and neonatal autopsy rates, cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. RESULTS: The extended perinatal mortality (including stillbirths and neonatal deaths) rate (EPMR) was 55.2 per 1,000 in 1982-1994 in twins compared with 9.9 per 1,000 in singletons. The relative risk for twin compared with singleton deaths was 5.6 (95% CI 5.1-6. 1) being highest for immaturity (12.9, 95% CI 11.1-15.0). A significant decrease in the EPMR occurred in both twins and singletons in 1988-1994 compared with 1982-1987. The EPMR decreased mainly due to a reduction of deaths from antepartum asphyxia in twins and intrapartum asphyxia and trauma in singletons, as well as a reduction in congenital malformations in both groups. In both twins and singletons, birthweight-specific mortality rates improved between 1982-1987 and 1988-1994. CONCLUSION: The higher relative risk for twin deaths remained stable due to a similar decrease in the EPMR for both twins and singletons. The cause-specific relative risk in twins declined for antepartum asphyxia. The mortality rate resulting from lethal congenital malformations decreased in twins and singletons mainly due to earlier detection and subsequent termination of pregnancy.

Birth Weight↗
PubMed2000

Mammographic screening in women with a family history of breast cancer: some results from the Swedish two-county trial.

BACKGROUND: The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without. In the invited arm of a randomised trial of breast cancer screening, data on family history of breast cancer were available on 29.179 women aged 40-74 attending for screening. Among those women, 358 were diagnosed with breast cancer during the trial. METHODS: Those with and without a family history were compared with respect to mammographic parenchymal pattern, interval cancer rates, mean sojourn time and sensitivity of screening. In the 358 cancers, the effect of family history was estimated on survival, incidence of advanced cancers and their relationship to screen detection. RESULTS: A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40-49. Interval cancer rates were higher in women with a family history, and in older women at least, mean sojourn time was shortened in women with a family history (1.89 years compared to 2.70). Survival was better (although not significantly so) in cancers in women with a family history (relative hazard=0.52) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers (relative hazard=2.72) independently of family history. Similarly, interval cancers tended to be larger, and worse malignancy grade in those with and without a family history of breast cancer. CONCLUSIONS: These results suggest that the policy often adopted of annual screening for woman aged 40-49, with a family history of breast cancer, is a reasonable one, and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history.

Adult↗
PubMed1998

A systematic review and meta-analysis of family history and risk of ovarian cancer.

OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in women with various categories of family history. DESIGN: A meta-analysis of all published case-control and cohort studies. METHODS: Pooled relative risk estimates were calculated for the case control studies, using the Mantel-Haenzel method. These estimates were combined with the relative risks from the cohort studies. The pooled estimates of relative risk were used to estimate lifetime risks of ovarian cancer from age 15 up to age 75, for various categories of family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of developing ovarian cancer were calculated for the categories of women with 1. an affected first degree relative; 2. an affected mother; 3. an affected sister; and 4. women with more than one affected relative. RESULTS: The relative risk to first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this relative risk declines with age. The relative risk to mothers of cases 1.1 (95% CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1), and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a substantially higher risk of developing ovarian cancer compared with women without such a history. However the risk is small for most categories of family history, except for the small number of individuals who have more than one affected relative.

Adult↗
PubMed1981

Maternal thyroid function and motor competence in the child.

Serum thyroid hormone levels were measured in women living in an area of severe dietary iodine deficiency in a remote region of Papua New Guinea. Levels of maternal hormone were found to be related to the motor competence of the women's offspring, who were aged between six years and 11 years 10 months at the time of assessment. Motor competence in the children was measured by two tests of manual dexterity which demanded speed and accuracy in performance. A significant correlation was obtained between the children's motor performance and maternal serum thyroxine levels, but not with maternal serum triiodothyronine levels. The implications of the findings for the pathogenesis of some forms of cerebral palsy are considered.

Child↗
PubMed1980

Outcome of pregnancies following the use of oral contraceptives.

The use of oral contraception by women doctors on the Medical Register for England and Wales in 1975 was studied and related to the outcome of their pregnancies. Nearly two thirds had used oral contraception at some time, but less than one third of their pregnancies had followed its use. Users tended to be younger at the time of the survey and to smoke in pregnancy more often. After allowing for these associations a poor outcome was just slightly more common in pregnancies occurring after OC use, particularly in conceptions occurring within a month or after a year of cessation. In contrast conceptions occurring in the 2nd or 3rd month after cessation had an unusually favourable outcome. It therefore seems likely that at least some of this weak association between oral contraception and poor outcome may be explained by factors that determine the length of time it takes to conceive. Overall it seems that any real risk to pregnancies conceived after cessation of oral contraception must be very small and outweighed by the undoubted advantages of its use.

Adult↗
PubMed1978

Fetal loss, gravidity, and pregnancy order.

An investigation of the reproductive history of 3068 women doctors showed that the risk of fetal loss at a given pregnancy order varied with their gravidity--that is, the total number of pregnancies that has occurred before the survey. Fetal loss rates in even the first pregnancy varied with eventual gravidity in a J-shaped manner. They fell from 12.4% in women with only one pregnancy at the time of the study, to 5.7% in women with two, and then increased steadily to 36.8% in those with six pregnancies. This variation in risk remained when allowance was made for the incomplete nature of some of the reproductive histories. When gravidity was held constant, fetal loss rates decreased with each successive pregnancy. This finding conflicts with previous suggestions that the risk of fetal loss increase with pregnancy order and age.

Abortion, Spontaneous↗