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Biomedical subjects

G Engholm

Publications and source records attributed to G Engholm.

At least 73 records · Page 4Linked to original sources

Case-control study of risk factors for cervical neoplasia in Denmark. I: Role of the "male factor" in women with one lifetime sexual partner.

Possible risk factors for cervical cancer were investigated in 645 women, 20-49 years of age from Copenhagen, with histologically confirmed cervical cancer or carcinoma in situ and in 614 controls drawn at random from the female population of the same area. To study the role of the "male factor", monogamous cases and controls together with their husbands were invited for further examination. This included a personal interview, a blood sample for analysis of herpes simplex virus antibodies, and a penile swab for papillomavirus analysis. In total, 41 case couples and 90 control couples were enrolled (89% and 92% of eligibles, respectively). The most significant risk determinants were a history of genital warts in the male (RR = 17.9 for ever vs. never) and ever having used condoms (RR = 0.2). Other potentially important factors, although not statistically significant, were ever having visited prostitutes (RR = 2.6, p = 0.14), circumcision (RR = 0.3, p = 0.18), and a history of genital warts in the female (RR = 4.6), p = 0.09). Having a husband with a history of multiple sexual partners was also associated with an increased crude risk, but when adjustment was made for husband ever having had genital warts, use of condom, and age, no significant excess risk was observed. Human papillomavirus DNA, which was tested for with ViraPap and ViraType, was detected in one of the controls, and in only 2 case husbands. This study points to the importance of "high-risk males" for the development of cervical cancer in their sexual partner; the results support the infectious nature of the disease.

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Cancer of the lung and urinary bladder in Denmark, 1943-87: a cohort analysis.

National data from 1943 to 1987 on the two most frequent tobacco-related cancers in Denmark, lung and bladder cancer, were analyzed with multiplicative Poisson models. The temporal trends in the cohort-specific risks for both sites and sexes were similar: the risks increased in the beginning of the period covered by the analysis, but then levelled off; and there was no increase among cohorts born after circa 1930. Women experienced a smaller increase during the period covered by the analysis in the cohort-specific risk for bladder cancer than men (3.7 cf 6.1 times), whereas the overall increase in lung-cancer cohort-specific risk was the same for both sexes. The difference could not be explained by trends in tobacco consumption, types of tobacco consumed, or occupational exposures. On the basis of these findings, it is suggested that women may be less susceptible than men to developing bladder cancer from tobacco smoking.

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Cancer risk among staff at two radiotherapy departments in Denmark.

In comparison with the general Danish population, the relative risk (RR) for cancer among staff members employed in two radiotherapy departments in Denmark during 1954-1982 and alive on 1 April 1968 was assessed by linkage to the Danish Cancer Registry. All staff had been monitored with film dosimeters for exposure to radiation. The study cohort consisted of 4151 persons, accruing 49553 person-years at risk. The collective radiation dose was 76.54 manSv and the mean dose 18.4 mSv. A total of 163 cancer cases were observed with 152.3 expected. The risks for cancers usually considered to be radiogenic were not elevated. A significant excess of prostatic cancer was observed (five cases, relative risk, 6.02; 95% confidence interval, 1.94-14.06); this is likely to be a chance finding. No relation was observed between radiation dose or years of exposure and cancer risk, but a weak non-significant increase in risk with time since first exposure was seen.

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A collaborative study of cancer incidence and mortality among vinyl chloride workers.

A large European multicentric cohort study has been coordinated by the International Agency for Research on Cancer with the objectives of investigating the dose-response relationship between liver cancer and exposure to vinyl chloride and assessing cancer risk for sites other than the liver. A nearly threefold increase in liver cancer was detected on the basis of 24 observed deaths and 8.4 expected (standardized mortality ratio 286, 95% confidence interval 186-425). The excess from liver cancer was clearly related to time since first exposure, duration of employment, and estimated ranked and quantitative exposures. Other cancer sites investigated on the basis of a priori hypotheses were either not in excess (lung) or apparently unrelated to the exposure variables (brain and lymphoma).

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[Sexual habits of women aged 20-39 years. A comparison of 3 population-based studies from Nyköbing Falster, Copenhagen and Nuuk/Godthåb].

The sexual habits in women aged 20-39 years chosen at random were investigated. A total of 513 women from Copenhagen participated while there were 586 women from Nykøbing Falster and 661 women from Nuuk (Godthåb) in Greenland. The women from Copenhagen replied to a questionnaire investigation while women from the other two regions were interviewed personally. The age of commencement of sexual activity was considerably lower in Godthåb in women of all age groups than in Copenhagen and Nykøbing Falster e.g. the prevalence of women with age on commencement of sexual activity less than or equal to 16 years was 70-80% in Godthåb while the corresponding figures for Copenhagen were 50-60% and for Nykøbing Falster 30-58%. Comparison with previous investigations revealed that the average age at the first coitus showed a tendency to decrease in all three regions during the past 20-30 years. The difference in the age at the first coitus between a provincial town (Nykøbing Falster) and a city (Copenhagen) was present only in the case of women in the oldest age group (35-39 years) and a geographical levelling appears to have occurred in the younger age groups (20-24 years) concerning the age at commencement of sexual activity. Women in Greenland had significantly more partners than women in the two South Danish regions. In Godthåb, the prevalence of women with greater than or equal to 40 partners was thus 22.4% while the prevalences in Copenhagen and Nykøbing Falster were 3.5% and 0.3%, respectively. The prevalences of women with 0-1 partners were 1.7%, 10.7% and 20.4%, respectively in Godthåb, Copenhagen and Nykøbing Falster.

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Risk factors for cervical human papillomavirus and herpes simplex virus infections in Greenland and Denmark: a population-based study.

Risk factors for genital human papillomavirus (HPV) types 6/11 and 16/18 and any HPV type as well as for herpes simplex virus type 2 (HSV-2) infections were investigated in a population-based study of 1,600 randomly selected women (20-39 years) from Godthåb (native, Nuuk), Greenland, and Nykøbing Falster, Denmark. A total of 586 Greenlandic women and 661 Danish women were included, respectively. They all had a personal interview and a gynecologic examination with cervical smear and swab for HPV analysis (filter in situ hybridization). Moreover, a blood sample was obtained for analysis for HSV-2 antibodies by enzyme-linked immunosorbent assay. In view of the general concept of HPV as a sexually transmitted virus, it is unexpected that women with "multiple" partners revealed a significantly lower risk for all types of HPV than did women with "few" partners, the odds ratio (OR) being 40-60% decreased in women with greater than or equal to 30 partners compared with women who had 0-4 sexual partners. In contrast, the risk for HSV-2 infection was significantly increased among women with early age at first sexual intercourse (OR = 2.9 for age less than or equal to 13 vs. 14-16 years) and multiple partners (OR = 2.6 for greater than or equal to 20 vs. 0-4 partners) (hereafter referred to as "high sexual activity" as well as with an increasing number of sexually active years with an unprotected cervix (i.e., without the use of barrier contraceptives) (OR = 2.0 for greater than or equal to 15 vs. 0-9 years). The results of this study thus demonstrate a surprising risk pattern for HPV types 6/11 and 16/18, but a pattern for HSV-2 in line with that to be expected for a sexually transmitted virus. This could indicate the existence of factors, especially in women with high sexual activity, which interfere with the expression of HPV or with the ability to detect it and/or that HPV may be transmitted by means other than sexual contact.

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Laryngeal cancer in Denmark: a nationwide longitudinal study based on register linkage data.

To identify high and low risk groups for laryngeal cancer in Denmark, all individuals aged 30-74 in the 1970 census were followed up over 10 years. Census data were linked with the Central Population Register to identify persons who died or emigrated during the follow up, and with the Danish Cancer Register to identify cases of laryngeal cancer. Individuals were categorised according to sex, age, and sociodemographic characteristics as declared on the census forms. A multivariate analysis was carried out by means of multiplicative Poisson models. The study showed that the risk of laryngeal cancer was strongly related to sociodemographic factors. The risk for skilled workers living in Copenhagen (relative risk (RR) 4.76, 95% confidence interval (CI) 3.61-6.28) was estimated to be almost five times higher than the risk for men self employed in agriculture and living in rural areas. The variation in the risk of laryngeal cancer is not fully explained by known variations in tobacco and alcohol consumption, and this study highlights additional risk factors particularly related to occupation and marital state.

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Abnormal Papanicolaou smear. A population-based study of risk factors in Greenlandic and Danish women.

Possible risk factors for abnormal Papanicolaou smear were investigated in a population-based cross-sectional study. From Nuuk (Greenland) and Nykøbing Falster (Denmark), random samples of 800 women aged 20-39 years were drawn. Totals of 586 and 661 women were included in Greenland and Denmark, respectively. All women went through a personal interview, and had a gynecologic examination including a PAP smear and cervical swab for HPV analysis. A blood sample was taken for analysis of HSV type specific antibodies. Multiple sexual partners was the most important risk factor for abnormal cervical cytology (OR = 4.2). An infectious etiology was also indirectly supported by a relatively protective effect of barrier contraceptive methods (OR = 0.6). The simultaneous finding of HPV 16/18 as a significant risk factor (OR = 2.4) cannot be taken uncritically as support for a causal effect of this HPV type, since such a relationship between cytological changes of the cervix and HPV infection could also emerge if the positive PAP smear was not just a measure of intra-epithelial neoplasia but also an expression of the infection itself on the cervix.

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Body size and cancer of the testis.

In the search for possible causes for the enormous increase in testicular cancer incidence in Denmark, we tested the hypothesis that a high fat or calorie intake in adolescence and consequently relative obesity is a promotional factor for testicular cancer. A total of 438 cases and three controls for each case were included in the study. Data originated from health examination of men liable for military service. Data were analysed by logistic regression analysis. No systematic statistically significant differences in body measurements [height, weight and body-mass index (weight/height2)] could be shown. Rather than being obese a slight trend was observed towards the future victims of testicular cancer being lighter, smaller and thinner than unaffected controls.

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Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

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Effect of organized screening on incidence and mortality of cervical cancer in Denmark.

Pap smears were used only on a limited scale in Denmark until the late 1960s. Since then smears have been taken both in organized screening programs and outside the programs by general practitioners, private gynecologists, and hospital wards. The present smear-taking activity is equivalent to an average of one smear every second year per woman. As the responsibility for health care rests with the counties in Denmark, differences are found between the counties both concerning organization of screening programs, and concerning the overall level of the smear-taking activity. An analysis using multiplicative Poisson models on county-based incidence and mortality data for women aged 30-59 years in 1963-1982 showed a statistically significant effect of organized screening in reducing both the incidence (RR = 0.67; 95% CI, 0.61-0.73), and the mortality (RR = 0.68; 95% CI, 0.59-0.78) of cervical cancer from 5 years after introduction of an organized screening program. The level of overall smear-taking activity was found to be of limited importance when organized screening was taken into account.

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The Danish case-control study of cutaneous malignant melanoma. I. Importance of host factors.

The relationship between cutaneous malignant melanoma and possible host factors was investigated in a population-based case-control study from East Denmark over a 3-year period. A total of 474 melanoma patients and 926 population controls aged 20-79 years were interviewed. Patients with lentigo maligna melanoma were not included. The major constitutional risk factors were: number of raised naevi on the arms (RR = 5.1 for 5+ vs. none), degree of freckling (RR = 2.9 for many vs. none), and light hair colour (RR = 1.7 for blond/fair vs. dark brown/black), which were independent of one another. An apparent synergy between number of raised naevi on the arms and degree of freckling was found. Thus, persons at high risk of melanoma may be identified by a simple assessment of naevi and degree of freckling. No significant difference was found between superficial spreading melanoma and nodular melanoma with regard to the most important host factors.

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Trends in cutaneous malignant melanoma in Denmark 1943-1982 by anatomic site.

Time trends in the incidence of cutaneous malignant melanoma were examined by analysing data from the Danish Cancer Registry, 1943-1982, by sex and subsite for 3509 male and 5305 female cases. The age-standardized incidence rate for cutaneous malignant melanoma for men and women in Denmark increased by five- to six-fold between 1943 and 1982. The increase varied by site; a particularly pronounced elevation was seen for tumours of the trunk in both men and women and of the leg in women. A statistical analysis of the effects of age, time and cohort showed steep increases in risk for progressively younger birth cohorts. This association was particular pronounced for sites other than the face, scalp and neck; for the latter sites, there was a much smaller increase for younger cohorts.

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High and low risk groups for cancer of colon and rectum in Denmark: multiplicative Poisson models applied to register linkage data.

Multiplicative Poisson models were used to identify subgroups of the Danish population at high and low risk of developing cancer of the right or left side of the colon, and cancer of the rectum. The analysis was based on cross-linked data from the 1970 census and the Danish Cancer Registry, where a 10-year follow-up period yielded some 20,000 colo-rectal cancers, in approximately 2.5 million persons. The risk of cancer of the right side of the colon in longer educated men living in apartment houses was almost twice as high as in farmers living in single family houses (relative risk 1.84; 95% confidence interval 1.42-2.37). A two-fold ratio (RR 2.18; 95% CI 1.70-2.62) was also seen in the risk of cancer of the left side of the colon between men with longer education in Greater Copenhagen and farmers in Jutland. The annual number of colon cancer cases in men in Denmark could be reduced by 27% if the incidence for all men was equal to that found for the low risk group of farmers.

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Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

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Bowen's disease and internal malignant diseases. A study of 581 patients.

In a retrospective study of 581 patients with a diagnosis of Bowen's disease (BD) treated over a 40-year period, we traced patient records to identify later diagnoses of nonskin cancer. Fifty patients had nonskin cancer, as against an expected number of 40, but this difference was not significant. The lack of association was equally true for BD on sun-exposed and non-sun-exposed skin. Our findings support the view that BD is not a skin marker for internal malignant disease.

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Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

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