Search PubMed⌕ Search

Biomedical subjects

J Cuzick

Publications and source records attributed to J Cuzick.

At least 55 records · Page 3Linked to original sources
PubMed2000

Future possibilities in the prevention of breast cancer: breast cancer prevention trials.

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed, of which three have reported efficacy results. A fifth trial using raloxifene has also been reported. The largest tamoxifen trial showed approximately 50% reduction in breast cancer incidence in the short term, but the two smaller trials did not find any reduction. Greater agreement exists for side effects; incidences of thromboembolic disease and endometrial cancers are raised approximately threefold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a meta-analysis indicates that all results are compatible with a 40% reduction in short-term incidence. Several important questions remain regarding the clinical implications of this result, including the effect on mortality, the appropriate risk groups for chemoprevention and the long-term effects on incidence. Continued follow up of these trials is crucial for resolving these issues.

Adult↗
PubMed2000

Psychosocial influences on older adults' interest in participating in bowel cancer screening.

BACKGROUND: As part of a multicenter, randomized controlled trial of the efficacy of flexible sigmoidoscopy for the prevention of bowel cancer, an investigation of the predictors of screening interest was carried out in a subsample of older adults. METHOD: The aim of the study was to establish the predictive power of the Health Belief Model (HBM) and to evaluate the contribution of HBM elements in mediating the effect of other demographic and health variables which have been found to be associated with screening interest and participation. A total of 5,099 participants were sent a postal questionnaire which examined screening interest, attitudes toward screen ing (benefits and barriers), perceived bowel cancer risk, bowel cancer worry, bowel symptoms, health status, state anxiety, and optimism. A total of 3,648 questionnaires were returned completed, giving a response rate of 71.5%. RESULTS: The results showed that threat, barriers, and benefits explained 47% of the variance in interest. Demographic and health variables were also associated with screening interest, although most of their effect was mediated by the HBM constructs. DISCUSSION: This community study in older adults showed a high level of interest in participating in screening. The large sample size provided the opportunity to test the value of the HBM model and to examine mediation of demographic and health variables. The HBM proved to be a good model of screening interest. These results further our understanding of the decision processes in participating in cancer screening and point to directions to increase the level of participation in community samples.

Attitude to Health↗
PubMed2000

A brief review of the current breast cancer prevention trials and proposals for future trials.

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed of which three have reported efficacy results. A fifth trial using raloxifene has also been published. The largest tamoxifen trial shows approximately a 50% reduction in breast cancer incidence in the short term, but the two smaller trials have not found any incidence reduction. Greater agreement exists for side-effects - thromboembolic disease and endometrial cancers are raised about 2 to 3-fold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a meta-analysis indicates that all results are compatible with a 42% reduction in short-term incidence. Several important questions remain about the clinical implication of this result, including the effect on mortality, the appropriate risk groups for chemoprevention and the long-term effects on incidence. Continued follow-up of these trials is crucial for resolving these issues.

Adult↗
PubMed2000

Genotype/phenotype and penetrance studies in melanoma families with germline CDKN2A mutations.

Patients with a family history of melanoma are at increased risk of this tumor. Those family members who also have the atypical mole syndrome are commonly targeted for screening in the belief that they are more likely to be mutant gene carriers. We have correlated the atypical mole syndrome phenotype and gene carrier status in five families with germline CDKN2A mutations and shown that family members with the atypical mole syndrome were three times more likely to be mutant gene carriers than their relatives who did not have the atypical mole syndrome (odds ratio 3.4; confidence interval 1.0-11. 1), supporting the view that CDKN2A is nevogenic. Individual characteristics which best predicted mutant gene carrier status were: nevi on the buttocks (odds ratio 4.4; confidence interval 1. 6-12.4), nevi on the feet (odds ratio 4.2; confidence interval 1. 4-12.5), total nevus number being at least 100 (nevi > or = 2 mm in diameter) (odds ratio 3.4; confidence interval 1.0-11.1) and two or more clinically atypical nevi (odds ratio 3.1; confidence interval 1. 1-9.0). Gene carriers were also significantly more likely to have noticeable freckling and possibly also Fitzpatrick skin types 1-3. The overlap between gene carriers and nongene carriers was, however, marked: the atypical mole syndrome did not clearly differentiate mutant gene carriers from those with a normal gene. This study is of significance to clinicians as the clinical practice of using the atypical mole syndrome to identify particular family members for surveillance is shown to be inappropriate. Until formal gene testing is available, all members of families with an excessive number of melanoma cases should be treated as potential mutation carriers at increased risk of melanoma.

Genes, p16↗
PubMed2000

Association between high-risk HPV types, HLA DRB1* and DQB1* alleles and cervical cancer in British women.

Cervical scrapes from 116 British women referred with cervical cancer were tested for the presence of high oncogenic risk human papillomavirus (HPV) genotypes (HPV(hr)). Ninety-four per cent of the scrapes had one or more of these virus types and 66% were HPV16-positive. HPV18 was more frequent in adenocarcinoma. No evidence was found for an increased cancer risk associated with the HPV16 E6 350G variant. The HLA DRB1* and DQB1* alleles in these women and in 155 women with normal cytology and negative for HPV(hr) DNA were compared. DQB1*0301 alone (2P = 0.02) and in combination with DRB1*0401 (2P = 0.02) was found to be associated with cervical cancer. This was more marked in cancers positive for HPV types other than HPV16. In contrast, DRB1*1501 alone and in combination with DQB1*0602 was not significantly elevated in cancers overall, but did show some excess in HPV16-positive cancers (2P = 0.05), associated with HPV16-positive cervical cancers. Taking all cancers together, a marginally significant protective effect was found for DQB1*0501 (2P = 0.03) but no protective effect could be seen for DRB1*1301.

Adenocarcinoma↗
PubMed2000

A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions.

A systematic review of the available evidence on the role of HPV testing in cervical screening has been published by the Health Technology Assessment Committee of the UK Department of Health. The review summarized relevant data on testing methods, natural history, and prevalence of the virus in different disease groups. Cost-effectiveness modelling was undertaken. Ten major conclusions were reached and are reported here. The key conclusions were that HPV testing was more sensitive than cytology, but that there were concerns about specificity, especially in young women. The increased sensitivity led to a recommendation that HPV testing be introduced on a pilot basis for women with borderline and mild smears. HPV testing has great potential as a primary screening test, but large trials are needed to properly evaluate this application and to determine if its introduction can reduce invasive cancer rates. There is an urgent need to undertake a large trial of HPV testing in conjunction with other new technologies (liquid-based cytology and computer-assisted cytology reading) to determine the best way to integrate them into ongoing screening programmes. A range of issues including the age to start and stop screening, the appropriate screening interval, the role of self-sampling for HPV testing and the choice of primary test (HPV and/or cytology) require further evaluation.

Adult↗
PubMed2000

Photoadaptation to ultraviolet (UV) radiation in vivo: photoproducts in epidermal cells following UVB therapy for psoriasis.

BACKGROUND: Ultraviolet (UV) radiation is mutagenic and induces specific DNA lesions in human skin that are often found at dipyrimidine sites. These photoproducts are likely to be biologically relevant regarding skin carcinogenesis, as p53 mutations in skin tumours are most often found at these UV radiation-specific sites within DNA. Psoriasis patients receiving long-term phototherapy are at an increased risk of non-melanoma skin cancers. OBJECTIVES: The aim of this study was to quantify DNA photoproducts in human epidermis in vivo following consecutive doses of UVB and to investigate variations in DNA damage according to skin type, UVB dose and age. METHODS: Eleven psoriasis patients receiving UVB phototherapy three times a week were recruited and underwent skin biopsies on a non-sun-exposed site before starting phototherapy and after three, nine and 18 UVB exposures. A biopsy was also taken at least 4 weeks after stopping phototherapy. DNA was extracted from separated epidermis and three types of photoproducts were quantified using a novel 32P high-performance liquid chromatographic technique. RESULTS: The mean level of cyclobutane dipyrimidine dimers (CPDs) after three doses of UVB (dose range 0.03-0.15 J cm-2) was 3.2 (range 0.8-8.9) photoproducts per 106 normal nucleotides for TT=T dimers and 4.5 (range 0-14) per 106 normal nucleotides for TT=C dimers. The mean levels of TT-C 6-4 photoproducts after three doses of UVB were very low (0.2, range 0-1.8). Overall, the levels of TT=T and TT=C reached a plateau at three exposures and were found to decrease for subsequent exposures despite increasing UVB doses. Skin type was negatively associated with mean levels of CPDs. However, significant differences in levels of photoproducts were seen between individuals, even after adjusting for skin type. No association was found between challenge dose of UVB and photoproduct yield in this study. CONCLUSIONS: This study showed a great individual variation in the accumulation of DNA photoproducts following exposure to repetitive doses of UVB. Photoadaptive responses of human skin involving DNA repair, tanning and epidermal thickening are likely to explain the overall lack of increase in DNA lesions throughout phototherapy. This in vivo study confirms that psoriasis patients produce a significant amount of DNA photolesions at suberythemal doses of UVB. Further work is needed to investigate which host factors are most likely to predict susceptibility to UV radiation-induced DNA damage.

Adult↗
PubMed2000

Predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial.

OBJECTIVE: To investigate predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial. DESIGN: Prospective design in which participants completed a postal questionnaire before being sent their invitation for screening. SETTING: Welwyn Garden City and Leicester, United Kingdom. PARTICIPANTS: A total of 2758 patients aged 55 to 64, registered with general practices in the two centres, who (a) expressed interest in having the screening test, (b) completed a postal questionnaire, and (c) were subsequently invited for screening. MAIN RESULTS: The attendance rate among questionnaire responders was 76.1%. Multiple logistic regression analysis yielded a final model that included nine independent predictors of attendance. Patients with the following characteristics were more likely to attend: men; home owners; non-smokers; those who had regular check ups at the dentist; those with better subjective health; those who minded less about having medical tests; those who said they would definitely rather than probably take up the offer of sigmoidoscopy screening; and those who perceived less barriers and more benefits to having the test. CONCLUSIONS: The findings are broadly consistent with previous studies of screening participation, although subjective health emerged as an important predictor in this study. There was no evidence for "reverse targeting": attenders were not at lower (or higher) risk for colorectal cancer compared with non-attenders. The findings relating to attitudes and beliefs could be used in efforts to improve attendance, for example by developing information leaflets that address barriers to screening. Other findings could be used to target interventions to subgroups that have relatively low rates of screening participation.

Age Factors↗
PubMed1999

Screening for cancer: future potential.

Much progress has been made in cancer screening over the past decade, but a great deal more needs to be done if screening is to make a major impact on worldwide cancer mortality. Where fully implemented, cytological screening for cervical precursor lesions has had a major impact on mortality. However, the cost and required infrastructure levels are high, and new approaches are needed if screening is to be effective in the developing world. Testing for the human papillomavirus and automated liquid based cytology offer great promise to improve quality, reduce overall cost and make screening more viable generally. Breast screening has been less successful, although useful mortality benefits have been achieved in women aged over 50 years. Full implementation in countries that can afford it will save lives, but radical new approaches will be needed to conquer breast cancer. Colorectal cancer screening offers the best hope of a major reduction in cancer mortality over the next decade. Less certainty exists about screening for other major cancers such as lung, prostate and ovary, but a range of potential approaches merit investigation.

Breast Neoplasms↗
PubMed1999

Screening for cancer: future potential.

Much progress has been made in cancer screening over the past decade, but a great deal more needs to be done if screening is to make a major impact on worldwide cancer mortality. Where fully implemented, cytological screening for cervical precursor lesions has had a major impact on mortality. However, the cost and required infrastructure levels are high, and new approaches are needed if screening is to be effective in the developing world. Testing for the human papillomavirus and automated liquid based cytology offer great promise to improve quality, reduce overall cost and make screening more viable generally. Breast screening has been less successful, although useful mortality benefits have been achieved in women aged over 50 years. Full implementation in countries that can afford it will save lives, but radical new approaches will be needed to conquer breast cancer. Colorectal cancer screening offers the best hope of a major reduction in cancer mortality over the next decade. Less certainty exists about screening for other major cancers such as lung, prostate and ovary, but a range of potential approaches merit investigation.

Adult↗
PubMed1999

Mutation testing in melanoma families: INK4A, CDK4 and INK4D.

The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified.

Carrier Proteins↗
PubMed1999

HPV testing in primary screening of older women.

Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml(-1) cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme.

Adenocarcinoma↗
PubMed1999

Interaction, subgroup analysis and sample size.

The term "interaction" has both statistical and scientific connotations that do not always coincide. Multistage models are used as a bridge between these two viewpoints and as a way of illustrating the different types of qualitative interaction. The most important type of interaction for metabolic polymorphisms is between a genetic trait and an environmental or lifestyle exposure. In some cases these factors act multiplicatively on the risk ratios and so do not interact in the statistical sense. Nevertheless, the risk can be much higher when both are present. Interactions present severe problems of interpretation, as naive comparisons in subgroups can be very misleading and can produce false positive results because of the large number of comparisons. Methods for combating this are discussed. The main requirement, however, is for a substantially larger sample size than would be required for estimating the main effects.

Bayes Theorem↗