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Biomedical subjects

J Cuzick

Publications and source records attributed to J Cuzick.

At least 19 recordsLinked to original sources
PubMed1992

Ingested arsenic, keratoses, and bladder cancer.

A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945-1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).

Arsenic↗
PubMed1992

Mild cervical dyskaryosis: safety of cytological surveillance.

How best to manage women who are found on cervical screening to have mild dyskaryosis remains controversial. Cytological surveillance misses some lesions picked up by colposcopy, but colposcopy is emotionally traumatic for women, the majority of whom will have a normal result. To determine what proportion of lesions are missed by cytological surveillance, and whether any abnormalities persist after colposcopy, we studied, by means of colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia (CIN) and subclinical human papillomavirus infection (HPVI) in two groups of patients who had had a first smear showing mild dyskaryosis at least 24 months earlier. One group was recruited from a centre practising cytological surveillance, with colposcopy for patients showing persistent or progressive cytological abnormality. The other group all had early colposcopy and treatment. Of 214 patients recruited into the cytological surveillance group, 70 (33%) had been referred for colposcopy within 24 months. Colposcopy of the remaining 144 (after a mean interval of 27 months from presentation) revealed that 54 (38%) were disease free, 64 (44%) had HPVI/CIN1, 8 (6%) had CIN2, and 18 (12%) had CIN3. A smear at that time identified 12 of the 18 (67%) with CIN3 as needing close cytological follow-up (1 patient) or prompt referral for colposcopy (11 patients). 137 women in the early colposcopy group attended for the study colposcopy (after a mean interval of 32 months from presentation). 37% were found to have some abnormality persisting after an earlier colposcopy, but none had CIN3. Cytological surveillance of mild dyskaryosis resulted in a 12% risk of patients having a small CIN3 lesion after 2 years, but this risk was reduced to 4% by the addition of a third repeat smear 12 months after the second. With such a policy only about a third of women would require colposcopy, and the risk of missing serious underlying precancerous changes would be low.

Adult↗
PubMed1992

Human papillomavirus type 16 in cervical smears as predictor of high-grade cervical intraepithelial neoplasia [corrected].

The management of women with mild to moderately dyskaryotic cervical smears would benefit from a non-invasive test that predicts which women have high-grade cervical intraepithelial neoplasia. Detection of human papillomavirus type 16 (HPV16) DNA in cervical smears may be such a test. With the polymerase chain reaction (PCR), we estimated the amount of HPV16 DNA in cervical smears from 85 women referred for colposcopy because of abnormal cytology. An intermediate or high amount of HPV16 DNA predicted the presence of high-grade cervical intraepithelial neoplasia in a subsequent biopsy in almost 90% of patients irrespective of the cytological grade of the referral smear. This technique may allow early identification of those women with low-grade cytological abnormalities who have high-grade underlying cervical disease.

DNA, Viral↗
PubMed1992

Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.

BACKGROUND AND METHODS: Surveillance by repeated colonoscopy is currently recommended for patients with colorectal adenomas. We assessed the long-term risk of colorectal cancer after rigid-instrument sigmoidoscopy and polypectomy in 1618 patients with rectosigmoid adenomas (tumor of the rectum or distal sigmoid colon) who did not undergo surveillance. A total of 22,462 person-years of observation were accrued (mean, 14 years per patient). RESULTS: The incidence of subsequent rectal cancer in these patients was similar to that in the general population (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.7 to 2.1). Most rectal cancers developed in patients whose adenomas had been inadequately removed; the risk was very low after complete removal. The risk of subsequent colon cancer depended on the histologic type, size, and number of adenomas in the rectosigmoid. Among 842 patients with a rectosigmoid adenoma that was tubulovillous, villous, or large (greater than or equal to 1 cm), colon cancer developed in 31 patients. The standardized incidence ratio was 3.6 (95 percent confidence interval, 2.4 to 5.0) overall and 6.6 (95 percent confidence interval, 3.3 to 11.8) if there were multiple rectosigmoid adenomas. Among the remaining 776 patients with only small, tubular adenomas (whether single or multiple), colon cancer developed in only 4 patients. The standardized incidence ratio in this group was 0.5 (95 percent confidence interval, 0.1 to 1.3). CONCLUSIONS: Follow-up colonoscopic examinations may be warranted in patients with tubulovillous, villous, or large adenomas in the rectosigmoid, particularly if the adenomas are also multiple. In patients with only a single, small tubular adenoma that is only mildly or moderately dysplastic (43 percent of our series), however, surveillance may not be of value because the risk of cancer is so low.

Adenoma↗
PubMed1992

32P-postlabelling analysis of DNA from human tissues.

DNA extracted from human lung, bladder, liver, pancreas, cervix and breast tissue samples taken at autopsy (37 sample sets) was analysed by the nuclease P1 enhancement modification of the 32P-postlabelling assay for levels of aromatic carcinogen DNA adducts. Results were combined with those from a previous study for statistical analysis of 56 sample sets (32 male+24 female). A strong trend was seen for increased adduct levels in the lung DNA of smokers and a weak association for the bladder DNA of smokers compared to non-smokers. Aromatic adducts were also detected in other tissues.

Carcinogens↗
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗
PubMed1992

Risk factors for melanoma: site variation in minimal erythema dose.

Skin types 1 and 2, increased numbers of moles, and excessive intermittent sun exposure are known risk factors for cutaneous melanoma, but the inter-relationship between UV radiation exposure, moles and melanoma remains unclear. There is a noteworthy site variation in melanoma, it being more common on the lower leg in women and on the back in men. In order to determine whether this site variation could provide further clues to the pathogenesis of melanoma, we examined site variation in photosensitivity and its relationship to other known melanoma risk factors (number of moles, skin type and skin colour) in 25 healthy volunteers. A marked site variation in photosensitivity was found. The pale skin of the volar aspect of the forearm was markedly less photosensitive than the darker skin of the back. Females were more photoresistant than males on the lower legs even though this is the more common site for melanoma in women. There was some correlation between the number of moles and photosensitivity at the two sites.

Adult↗
PubMed1992

Methodologic issues in the chemoprevention of breast cancer.

Interest in preventing breast cancer has centered on two possible interventions--restriction of dietary fat intake and prophylaxis with tamoxifen. Uncertainty about the most important age at which fat intake should be reduced, severe problems in achieving compliance, and uncertainty about dietary fat intake as a risk factor make a trial of dietary fat restriction logistically very difficult, extremely expensive, and a very long-term enterprise with uncertain outcome. A trial of tamoxifen prophylaxis is not without its logistic difficulties and the outcome is by no means certain, but the prospects of getting a clear answer within 10 years are much better, and this would appear to be the most attractive option for preventing breast cancer at present.

Anticarcinogenic Agents↗
PubMed1991

The use of cervicography in a primary screening service.

The cervicography and concurrent endocervical brush smear results obtained in 1162 women screened at the Marie Stopes Clinic were analysed. Colposcopy and biopsy results were obtained for positive cases. A comparison was made with a group of 1007 women attending the same clinic for routine cytology only. Nearly 10% of women who were screened by cervicography had a technically defective cervicogram, the main single reason being that the view was obscured by blood. Routine cytology was positive in 1%, while cervicography was positive in 13%, where positivity was defined as a result leading to a recommendation for colposcopy. The false positive rate for cervicography was 26%. Even after adjustment, this difference was highly significant (P less than 0.0001).

Acetates↗
PubMed1990

DNA adducts in different tissues of smokers and non-smokers.

Purified DNA from human lung, liver, bladder, pancreas, breast and cervix has been analysed for DNA adducts using the nuclease P1 modification of the 32P post-labelling technique. Tissues were obtained at autopsy from 13 men and 6 women. Relatives were asked to provide information on smoking history for deceased subjects. All tissues examined except the breast had detectable adducts. In lung, bladder and pancreatic tissue a characteristic pattern of adducts was seen which has previously been reported as typical of cigarette-smoke-induced damage. Smokers and former smokers tended to have higher adduct levels than non-smokers in the tissues examined but this was only significant for the lung. There appeared to be considerable variation in adduct levels among smokers which could not be accounted for by duration or daily consumption level. Certain smokers had high adduct levels in all tissues examined, whilst in others high levels were only seen in some tissues. All cervical samples examined had detectable adducts. These results confirm the finding that cigarette smoking is associated with DNA damage in the lung and suggest that similar damage may be related to tobacco-induced neoplasms of other tissues.

Aged↗
PubMed1990

Case-control study of risk factors for cervical intraepithelial neoplasia in young women.

A case-control study of 497 women under age 40 diagnosed with cervical intraepithelial neoplasia (CIN) and 833 controls was done in the London area between 1984 and 1988 to examine whether known risk factors for invasive cervical cancer produced similar risks for CIN of different grades in young women. Cases of CIN III had a risk profile similar to that seen for invasive disease whereas CIN I cases were similar to the controls in all risk factors examined except a history of genital warts. Cases of CIN II were intermediate between the two. Among several indicators of sexual and reproductive behaviour, age at first childbirth and a history of multiple sexual partners were the strongest risk factors for CIN II and CIN III. Smoking had a strong and independent effect on the risk of CIN II and CIN III, but had only a limited effect for CIN I. Use of oral contraceptives was widespread in cases and controls, but length of use of oral contraceptives was not found to be a risk factor. A small protective effect of barrier contraception was observed.

Adolescent↗
PubMed1990

Palmar keratoses in family members of individuals with bladder cancer.

A total of 270 bladder cancer cases, 178 first-degree relatives and 127 spouses of the bladder cancer cases and 329 hospital controls were studied to evaluate the association between palmar keratoses, bladder cancer and environmental and genetic factors. Crude prevalences of keratoses in the 4 groups were 67, 54, 42 and 23%, respectively. Logistic regression models showed that bladder cancer patients had a raised risk of having palmar keratoses relative to hospital controls (odds ratio = 6.95; 95% CI: 4.77-10.12) whereas blood-relatives and spouses had significantly increased odds ratios only if the case in their family (or some other blood-relative) possessed keratoses. Among several environmental and behaviour factors, only cigarette smoking was significantly associated with increased risk (odds ratio = 2.32; 95% CI: 1.63-3.29). The data suggest a genetic component may influence the occurrence of palmar keratoses, but some unknown environmental agent appears to be causing the association between spouses.

Adult↗
PubMed1990

Anal cancer and marital status.

Anal cancer is a rare tumour in Britain and its epidemiology has not previously been studied in this country. Several studies from the United States have shown an association between single marital status at the time of tumour registration (as a marker of male homosexuality in these populations) and the incidence of anal cancer. This study has used registry information on martial status for anal cancer and for colon cancer (controls) from the Thames, West of Scotland and West Midlands Cancer Registries. The registry data on marital status was validated using death certificate information. The relative risk of developing anal cancer was found to be significantly increased in single men for all three registries individually and for the combined data sets (OR 2.2' 95% CI 1.8-2.8). This accords with the findings of similar studies in the United States and supports the hypothesis that a sexually transmissible agent may be involved in the aetiology of anal cancer. For women, being unmarried was found to be protective against anal cancer in the combined data sets (OR 0.6; 95% CI 0.5-0.8).

Adult↗
PubMed1990

Long-term prognostic value of serum beta 2 microglobulin in myelomatosis.

The prognostic value of serum beta 2 microglobulin (s beta 2m) measured at entry, at plateau and at 3-monthly follow-up times has been assessed for patients in the Medical Research Council's 4th and 5th Myelomatosis Trials. Analysis of 1014 patients confirmed the value of presentation s beta 2m of predicting survival in the short term but showed that predictive value was lost for subsequent survival in those patients who had survived for at least 2 years. However, measurements of s beta 2m taken during follow-up were predictive of subsequent survival. The predictive power of these follow-up measurements was very similar to that for the presenting measurement, and again they were only of value in predicting survival in the next 2 years.

Calcium↗