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Biomedical subjects

P Lenner

Publications and source records attributed to P Lenner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders.

A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0-3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0-59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.

Alleles↗
PubMed1999

Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study.

Sexual history is an established risk determinant for cervical neoplasia. It is not clear if human papillomavirus (HPV) exposure entirely explains the sexual behaviour-related risk or if other sexually transmitted agents may act as cofactors for HPV in carcinogenesis. The aim of this study was to elucidate whether HPV exposure or HPV persistence explains the sexual history-related risk of high-grade cervical intraepithelial neoplasia (CIN) using a population-based case-control study of most of the 254 women referred to colposcopy in the Vasterbotten county in Sweden because of an abnormal cervical smear during October 1993 to December 1995 and 320 age-matched women from the general population. The women were interviewed for sexual history and tested for presence of serum antibodies to HPV-16, -18 and -33 as well as for presence of HPV DNA in cervical brush samples. HPV-16, -18 and -33 seropositivity was specific for the corresponding type of HPV DNA, dependent on the lifetime sexual history and associated with a two- to threefold increased risk of CIN 3. There was no sexual history-related risk of CIN among HPV-seropositive women and adjustment for HPV DNA presence explained the sexual history-related risk of CIN. In conclusion, HPV exposure appeared to explain the sexual history-related risk of high-grade CIN.

Adult↗
PubMed1999

Women with false positive screening mammograms: how do they cope?

OBJECTIVES: To assess the long term psychological impact on women who were recalled for further investigation after mammography screening and to find any factors that might predict coping ability in order to identify those subjects who require additional support at an earlier stage. SETTING: Counties of Västerbotten and Västernorrland, Sweden. METHODS: A prospective design was used in which 252 recalled women completed questionnaires twice--once within a week of having received the all-clear and again at follow up six months later. A group of 1104 randomly selected, screen negative women were followed up in the same way for comparison. The questionnaire included the Psychological Consequences Questionnaire (PCQ) and basic sociodemographic data. The main outcome measure was the total score on the PCQ at six months. RESULTS: Of the 252 women, 235 (93%) completed both questionnaires. In the control group, 987 (89.4%) women responded. Six months after the all-clear, recalled women were still significantly more anxious (p < 0.001) than those who had been screened but not recalled. The strongest predictor of psychological distress at six months was the PCQ score at the first measurement. Other predictors were a low level of education, living in high density urban areas, and having only one child or no children at all. Widows appeared to cope better than other women. CONCLUSIONS: It is possible to define a group of women with false positive results who are already at risk of coping less effectively at the time of recall. Offering these women counselling or other types of support should be considered.

Adaptation, Psychological↗
PubMed1999

Low levels of serum vitamins A and E in blood and subsequent risk for cervical cancer: interaction with HPV seropositivity.

Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV.

Adult↗
PubMed1998

[Late side-effects are common after treatment of Hodgkin's disease. Muscular atrophy following radiotherapy is a neglected risk].

As Hodgkin's disease (HD) is amenable to treatment, especially in the young, the majority of patients are long-term survivors and late treatment-related side-effects can become a clinical problem. After a retrospective review of the records of 134 patients treated for HD at Umeå during the period, 1975-90, and 15-50 years of age at diagnosis, a questionnaire on late side-effects of treatment was sent to the 110 survivors, of whom 90 per cent responded. Many patients reported late side-effects such as hypothyroidism, dryness of the mouth, cardiac and pulmonary problems, and fertility disorders. Of the 20 patients who reported pain and weakness of the neck and shoulders, 18 had undergone mantle field irradiation (i.e., of the lymph nodes of the neck, axillae and mediastinum). If shown to be equally effective, lower irradiation doses might be given in future, thus perhaps minimising long-term side-effects.

Adult↗
PubMed1997

Infradiaphragmatic Hodgkin's disease: the Swedish National Care Programme experience. The Swedish Lymphoma Study Group.

A Swedish national care programme has provided guidelines for staging, treatment and follow-up of all patients with Hodgkin's disease (HD) since 1985. Between January 1985 and December 1992, 920 patients were reported and followed prospectively. Of a total of 533 patients with stage I and II disease, 484 presented with supradiaphragmatic HD and 49 (9%) with infradiaphragmatic HD. The median follow-up time was 4.3 yr (3.3-10 yr). Significant differences in average age (45 +/- 21 yr and 55 +/- 19 yr), male:female ratio (1.1:1 and 2.8:1) and B-symptoms (25% and 47%) were observed in patients with supra- and infradiaphragmatic HD, respectively. Forty-six patients with infradiaphragmatic HD were treated with a curative intention and 40 (87%) achieved a complete response. Eleven (28%) of the 40 patients have recurred and 8 patients have died of HD. Complete response rates and recurrence frequencies did not differ from those observed in patients with supradiaphragmatic HD. Mortality was, however, significantly higher (p = 0.001) in the infradiaphragmatic group; this was due mainly to poorer effects of salvage treatment in a elderly population. In this population-based study, patients with peripheral disease in stage IA respond well to inverted Y irradiation alone, whereas it appears to be important to give stage II patients chemotherapy or a combined modality treatment in order to avoid unacceptably high recurrence rates.

Adult↗
PubMed1997

Excess mortality from breast cancer in relation to mammography screening in northern Sweden.

OBJECTIVES: Previous randomised studies of mammography screening have shown a significant effect on breast cancer mortality, particularly in women aged 50-69 at randomisation. Breast cancer mortality has traditionally been studied by judgments on causes of death, either from cause of death registers or from medical records. In this study an alternative method was used, estimating the excess mortality associated with breast cancer. SETTING: In 1990 two counties of northern Sweden started population based mammography screening of women aged 40-74. The unscreened population in the two other counties of the same region were selected as controls. RESULTS: Excess mortality associated with breast cancer was lower in the screened population, and was discernible three to four years after the start of screening. The relative risk estimate, based on the cumulative excess number of deaths from breast cancer during 1990-95 in the screened versus the control population aged 40-74 (at diagnosis of breast cancer), was 0.72 (95% confidence interval (CI) 0.53 to 0.99). For women aged 50-69 it was 0.67 (95% CI 0.46 to 0.99). In the 50-69 age group the estimated excess number of deaths from breast cancer during 1995 was 17.0 per 100,000 women (95% CI 5.0 to 29.0) in the screened counties and 51.1 per 100,000 (95% CI 30.2 to 71.9) in the unscreened counties. CONCLUSIONS: Population based routine screening has substantial effects on breast cancer mortality in women aged 50-69. Estimation of excess mortality can be used in future studies to evaluate the effects of mammography screening on breast cancer mortality.

Adult↗
PubMed1996

Different HLA-DR-DQ haplotypes are associated with cervical intraepithelial neoplasia among human papillomavirus type-16 seropositive and seronegative Swedish women.

To analyze whether HLA may be a determinant of the risk of developing cervical cancer precursor lesions, the association between HLA and cervical neoplasia among HPV16-seropositive and -negative subjects was determined in a population-based cohort in the Västerbotten county of Northern Sweden. HLA genotyping of DR and DQ was done by PCR in 74 patients and 164 healthy controls matched for age, sex and area of residence. The presence of DQA1*0102 was weakly associated with cervical neoplasia in HPV16-seropositive patients. DQB1*0602 was weakly associated with disease in all patients, but was strongly increased among HPV16-seropositive patients compared to HPV16-seropositive controls. DR15 had an association with disease that was particularly strong among HPV16-seropositive subjects. The haplotype DQA1*0102-DQB1*0602 (DQ6) was also weakly associated with disease in all patients and significantly increased among HPV16-positive patients when compared to HPV16-positive controls. A similar association was seen when analysis was restricted to CIN 2-3 patients. DQA1*0501-DQB1*0301 (DQ7) was more common among HPV16-negative patients than among HPV16-negative controls and was also more common among HPV16-negative patients than among HPV16-positive patients. In conclusion, DQA1*0102-DQB1*0602 (DQ6) is associated with an increased risk of cervical neoplasia among HPV16-seropositive subjects and DQA1*0501-DQB1*0301 (DQ7) with an increased risk among HPV16-seronegative subjects.

Adult↗
PubMed1996

A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears.

To estimate the risk of developing cervical intra-epithelial neoplasia (CIN) among women exposed to human papillomavirus (HPV) type 16, we performed a prospective study in a population-based cohort of more than 15,000 women followed for 34.9 months. Seventy-four women developed CIN during follow-up and were matched for age, time of sampling and area of residence with 148 women who remained CIN-free during follow-up. The blood samples taken at enrollment were tested for serum antibodies to HPV types 16, 18 and 33 capsids. Cervical smears or biopsies were analyzed for the presence of HPV DNA by nested PCR using HPV general primers and by HPV 16- and 18-type-specific PCR HPV serology and HPV-PCR were in good agreement, particularly when the blood sample and the Pap smear were taken less than 6 months apart. HPV DNA was found in 88% of cases and 4% of controls, whereas HPV 16 DNA was present in 44% of cases and in 1 of 142 controls. HPV-16-seropositive women had a 3-fold increased risk of developing CIN. The risk was highest among women younger than 35 years of age, of whom an estimated 3.4% of HPV-16-seropositive and 0.5% of seronegative women developed CIN. Since the risk associated with HPV-16 seropositivity (a measure of past or present infection) was 35-fold lower than that of HPV DNA (present infection), most infections appear to be eliminated before CIN develops. In conclusion, HPV 16 infection does confer an excess risk of CIN development, and HPV DNA detection has a high predictive value for the presence of high-grade CIN.

Adult↗
PubMed1996

p53 polymorphisms and haplotypes in breast cancer.

Three polymorphisms in the human tumor suppressor gene p53 (BstUI and MspI RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patients with breast cancer and controls. A significant increase in the codon 72 BstUI A1 (pro) allele frequency (P = 0.016) and of individuals carrying the pro allele (pro/pro and pro/arg) (OR, 1.47; P = 0.01 4; 95 % CI, 1.08-2.00) was observed in breast cancer. This increase was most pronounced in highly differentiated breast cancer. Significant associations were found only in BstUI and haplotypes containing this polymorphism, which indicates that the codon 72 pro allele may be functionally involved in low malignancy breast cancer. The distributions of genotypic combinations in breast cancer patients and controls were significantly different (P = 0.005). Two BstUI-16 bp-MspI combinations were significantly overrepresented; 2-1, 1-1, 2-2 (OR, 1.61; 95% CI, 1.13-2.30) and 1-1, 2-1, 2-1 (OR, 2.94; 95% CI, 1.37-6.27).

Adult↗
PubMed1996

High-grade non-Hodgkin's lymphoma stage I. A retrospective study of treatment, outcome and prognostic factors in 213 patients.

In a retrospective study of 213 patients with high-grade non-Hodgkin's lymphomas clinical stage I, diagnosed 1985-1990, pretreatment prognostic variables and result of treatment were analysed. The median age of the patients was 67 years. Treatment consisted of radiotherapy in 61%, chemotherapy (10%) chemotherapy followed by radiotherapy (23%) and surgery alone (5%) of the patients. Complete response was achieved in 89% of the patients with estimated relapse-free survival at 5 years of 73%. Relative 5-year survival of all patients was 73%. After chemotherapy followed by radiotherapy the relapse rate was 15% compared with 29% after radiotherapy only. The 5-year relative survival differed between 58% and 74% in the treatment groups. Age, sex, nodal versus extranodal lymphoma, systemic symptoms, bulk of tumor and level of serum lactic dehydrogenase (s-LDH) were analysed as prognostic factors. In multivariate variate analysis, only age 65 years or older and elevated s-LDH were significant independent adverse prognostic factors.

Aged↗
PubMed1996

Treatment of Hodgkin's disease: the Swedish National Care Programme experience.

Since 1985 a Swedish National Care Programme has provided tailored principles for the diagnosis, staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report gives the rationale behind the recommendations and presents treatment results for 648 patients diagnosed between 1985 and 1989 after a median follow-up of 70 months. Two hundred and twenty-nine (35%) patients were over 60 years of age. Treatment results for patients below 60 years of age in early and intermediate stages were favourable, provided the recommendations were followed. In advanced stages, the outcome was inferior in patients with CS IIB bulky disease and stage IVB. The prognosis of elderly patients remains poor, although it is too early to evaluate any impact of revisions made in 1989. The tailored principles, which usually entail less staging and/or treatment than is generally the case in the early and intermediate stages, produced favourable results when applied to an unselected group of patients with HD. Only minor changes were made in the recommendations during the 1994 revision.

Adolescent↗
PubMed1995

Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer.

In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population-based controls were used to evaluate the disease-association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type-16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses most strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence intervals (CI) = 5.9-48.6], IgG against HPV16 virus-like particles (OR = 9.5, CI = 3.9-28.0) and IgG against the E1:19 epitope in the middle part of the E1 protein of HPV16 (OR = 7.7, C1 = 3.9-16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV-associated cancer.

Age Factors↗
PubMed1995

Serum antibody responses against human papillomavirus in relation to tumor characteristics, response to treatment, and survival in carcinoma of the uterine cervix.

To investigate whether the serum antibody responses to human papillomavirus (HPV) in cervical carcinoma were related to the clinical and histopathological features of the tumors and how the antibody responses were affected by treatment, pretreatment serum samples from 66 patients with carcinoma of the cervix were studied for the presence of IgA or IgG responses against six defined HPV epitopes. Posttreatment serum samples were drawn from the same patients 2-24 months after initiation of treatment. There was no significant correlation between pretreatment level of any of the investigated antibodies and clinical stage or differentiation of tumor. For the IgA responses to the epitopes 245:16 and 245:18 in the E2 protein there was a significant correlation between an increased pretreatment antibody level and a shortened survival. A high pretreatment value of IgA against 245:16 was also associated with the absence of any complete response after therapy. The antibody levels declined dramatically after therapy for most of the antigens studied. However, this decline was seen both among the 53 patients with complete remission and among the 13 patients with remaining or progressive disease. Thus, the investigated serological responses were not useful as tumor markers, since patients with progressive, late-stage disease may fail to mount an antibody response to these proteins. However, pretreatment levels of the serological responses to the HPV epitopes 245:16 and 245:18 were associated with prognosis in cervical cancer.

Adolescent↗