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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human papillomavirus (HPV) is found in close association with carcinogenesis of the uterine cervix. We applied a new in vitro gene amplification technology, the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cervical exfoliated cells. HPV infections were detected in 5 (16%) of 31 women with no pathological lesions of the uterine cervix (normal), 16 (24%) of 67 with cervical intraepithelial neoplasia (CIN) and 6 (38%) of 16 with invasive cervical cancer. Moreover, 10% formalin-fixed and paraffin-embedded tissue sections were prepared from the uterine cervix of these 27 women with PCR-proven HPV infection and were examined for the histological localization of HPV-DNA by in situ hybridization with biotin-labeled DNA probes of HPV types 6/11, 16/18 and 31/33/35. HPV-DNA type 16/18 was detected in 3 of 5 normal women, 2 of 4 CINs I, 2 of 3 CINs II, 6 of 9 CINs III and 6 of 6 invasive cervical cancers. HPV-DNA type 6/11 was detected in 6 of 6 condylomas. Viral DNA sequence was detected in the superficial cells of CIN I and II, and it was distributed through entire thickness layer of undifferentiated cells derived from CIN III and squamous cell carcinoma. In addition, the staining intensity became weak as the lesion progressed. These differences between lesions might be due to the difference in the viral form in the nuclei, ie whether an episomal or integrated form. Thus, an in situ hybridization technique with a biotin-labeled DNA probe as well as the PCR method is useful for the detection of HPV in clinical samples.
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PMID:[Detection of HPV DNA in the uterine cervical lesions by polymerase chain reaction and in situ hybridization]. 164 30

A study of 759 patients with invasive cervical cancer, 1,430 controls, and 689 sexual partners of the participants who declared that they were monogamous was conducted in Colombia, Costa Rica, Mexico, and Panama from January 1986 to June 1987, to evaluate the risk factors associated with this neoplasm. The principal risk factors identified were: initiation of sexual relations by the woman at an early age, number of stable sexual partners (relationships of more than three months' duration), number of liveborn children, presence of DNA from human papilloma virus (HPV) types 16 or 18, history of venereal disease, lack of exposure to early detection programs, deprived socioeconomic conditions, and number of sexual partners of the partners of the monogamous women. Smoking increased the risk in those women who were shown to have DNA from HPV types 16 or 18. Fifty percent of the patients and 29% of the controls said they had never had a cytological examination (Papanicolaou test). No association was observed between the presence of HPV and sexual behavior. The study showed the need for further research on the possible mechanisms involved in carcinogenesis and infection. The common denominators of the risk factors mentioned are underdevelopment and poverty, which affect broad sectors of these populations. Mass detection programs targeting high-risk groups can reduce the high incidence of cervical cancer in Latin America.
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PMID:[The risk factors of invasive carcinoma of the cervix uteri in Latin America]. 217 53

Australian women face a lifetime risk of dying of cervical cancer of 1 in 250. Current epidemiological evidence suggests that the age at 1st sexual intercourse and the number of sexual partners are important risk factors for cervical carcinogenesis. Other risk factors for invasive cervical cancer include cigarette smoking, deficiencies of dietary and plasma micronutrients, and oral contraceptive (OC) use. The recently documented increased risk of invasive cervical cancer associated with longterm OC use may in part reflect uncontrolled confounding by other factors, especially the likely association of OCs with greater exposure of the cervix to infectious agents such as human papillomavirus. Moreover, any association of present cancer with past use of OCs may not reflect the risk that is associated with the currently prescribed lower-dose agents. The profiles of risk appear to be similar for invasive carcinoma of the cervix and carcinoma in situ, confirming the view that carcinoma in situ is the main precursor lesion for invasive cancer of the cervix. A recent case-control study conducted in Sydney found a 50% increase in the risk of carcinoma in situ in ever users of OCs compared to never users, and the risk increased with increasing duration of OC use. The mode of the possible action of OCs on the risk of cervical cancer remains unclear. Recent studies have demonstrated that certain sex steroids directly activate viral DNA that is incorporated into the DNA of epithelial cells and that in vitro interaction occurs between such hormones and human papillomavirus type 16 DNA in the enhanced induction of carcinogenesis in cultured cells. This evidence that a sexually transmitted infectious agent contributes to the etiology of cervical cancer offers a clear direction for preventive action.
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PMID:Pills, partners and preventive prospects: in-situ cancer of the cervix. 254 23

A case-control study of uterine cervical cancer was conducted using 331 cases and 993 age-matched controls identified through the Missouri Cancer Registry during 1984-1986. Patients with smoking- or alcohol-related cancers were excluded from the control series. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (Cls) after adjustment for age, cigarette smoking, alcohol consumption, and stage at diagnosis. A dose-response relation was observed between intensity of cigarette smoking and invasive cervical cancer, with light and heavy smokers having elevated risks (OR = 2.2, 95% Cl = 1.4-3.6 and OR = 3.9, 95% Cl = 2.7-5.6, respectively). Former smokers had less elevated risk (OR = 1.7, 95% Cl = 1.0-2.9), a finding consistent with a greater effect of tobacco smoke on late-stage carcinogenesis. Similar results were obtained in age- and control site-specific analyses. Further, the age-specific data suggested a dose-response relation between duration of smoking and invasive cervical cancer. An association between alcohol consumption and invasive cervical cancer was not observed.
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PMID:Cigarette smoking and alcohol consumption in the aetiology of uterine cervical cancer. 280 54

The risk of invasive and intraepithelial cervical neoplasia in relation to the frequency of intake of the major sources of preformed vitamin A (retinol) and beta-carotene in the Italian diet was analyzed in a study of 392 cases of invasive cancer compared with 392 age-matched controls hospitalized for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 247 cases of cervical intraepithelial neoplasia compared with 247 controls found to have normal smears at the same screening clinics where cases had been identified. Women with invasive cancer consumed milk, green vegetables, and carrots less frequently, but no significant relation was noted for meat or liver. Consequently, estimated beta-carotene, but not retinol, intake was inversely and strongly related to the risk of invasive cervical cancer. Compared with women whose intake was over 150,000 international units (IU) per month, the relative risks were 3.0 for 100 to 149,999 and 4.7 for less than 100,000 IU. It was not possible to show that these relationships were incidental, since allowance for several identified potential distorting factors, including indicators of social status and the major risk factors for cervical cancer, did not materially modify the risk estimates. In contrast, no association emerged between any of the food items and vitamin A estimates considered and intraepithelial neoplasia. Thus, the results of this study can be interpreted in one of two ways: either some residual uncontrolled bias was responsible for the strong dietary correlates of invasive cervical cancer risk or beta-carotene (or any other correlate of a vegetable-rich diet) has effect on one of the later stages of the process of carcinogenesis, thus influencing the risk of invasive carcinoma but not of its precursors.
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PMID:Dietary vitamin A and the risk of intraepithelial and invasive cervical neoplasia. 337 43

The relation between major indicators of sexual habits (age at first intercourse and total number of sexual partners), history of selected venereal diseases, and cervical neoplasia was investigated using data from a case-control study of 206 cases of cervical intraepithelial neoplasia compared with 206 age-matched outpatient controls, and of 327 cases of invasive cancer compared with 327 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. The relative risks increased with decreasing age at first intercourse and increasing number of sexual partners both for intraepithelial and for invasive cancers. The effects of these two variables were independent, since they were only marginally affected by reciprocal adjustment, or by allowance for several other identified potential distorting factors. The negative association with age at first intercourse was particularly strong in the case of invasive cancers, with risk estimates over five-fold elevated for women reporting their first intercourse before age 18 compared with those aged over 22 years. This relation might be discussed in terms of multistage models of carcinogenesis, which predict that the incidence of epithelial carcinomas is a function of duration of exposure. In fact, when age was allowed for, the relative risks of cervical neoplasia were positively and strongly related with the total duration of the interval between age at diagnosis/interview and age at first intercourse. Clinical histories of several sexually transmitted diseases were positively associated with the risk of intraepithelial neoplasia. In particular, genital warts were reported by nine cases but no control subject. No such association, however, emerged for invasive carcinomas. Thus, the current findings confirm that, although intraepithelial neoplasia and invasive cervical cancer appear to share several important epidemiological features, the specific (infectious) agents implicated in dysplastic lesions probably differ to some extent from those causing invasive cancer.
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PMID:Sexual factors, venereal diseases, and the risk of intraepithelial and invasive cervical neoplasia. 375 77

The relationship between cigarette smoking and risk of cervical neoplasia was evaluated in a case-control study of 183 women with cervical intraepithelial neoplasia compared with 183 age-matched outpatient controls, and of 230 cases of invasive cervical cancer compared with 230 controls in hospital for acute conditions unrelated to any of the identified or suspected risk factors for cervical cancer. Current cigarette smoking was associated with an elevated risk of cervical intraepithelial neoplasia (relative risk = 1.76, 95 per cent confidence interval = 1.14-2.27) and of invasive cancer (relative risk = 1.69, 95 per cent confidence interval = 1.08-2.65). This association was only partially accounted for by a large number of identified potential confounding factors, including indicators of socioeconomic status and sexual habits. The risk increased with the number of cigarettes smoked and was apparently greater for women who started smoking at younger ages. The relative risk of intraepithelial neoplasia was elevated within 20 years after the start of smoking and showed little tendency to increase with increasing duration. On the other hand, the risk of invasive cervical cancer was apparently unaffected by smoking less than 20 years and increased steadily thereafter, reaching a point estimate of 3.63 after 40 years or more. If one assumes that intraepithelial neoplasia is an early stage of cervical cancer, this pattern of risk is consistent with the predictions from the multistage theory of carcinogenesis, if the effect of smoking is on one of the earlier stages. No obvious distorting factors, apart from the play of chance, is likely to produce such a risk pattern.
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PMID:Cigarette smoking and the risk of cervical neoplasia. 394 Apr 40

Plasma total glutathione (GSH) content (reduced plus oxidized) was estimated in varying grades of cervical intraepithelial neoplasia (CIN) and in invasive cervical cancer. The values were compared with age-matched control women. The results show significantly lower level of plasma GSH in CIN III and invasive cancer compared to controls (0.724 versus 1.082 and 0.622 versus 1.082 mumol/ml of plasma, P < 0.05). Further, the odds ratio analysis showed high plasma GSH content was found to be protective against the development of cervical cancer. The results suggest a plausible association of plasma GSH with cervical carcinogenesis. The quantitative changes occurring in plasma total glutathione during cervical carcinogenesis is a useful finding and might represent a systemic biochemical marker for precancerous and cancerous lesions of the uterine cervix.
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PMID:Decreased plasma glutathione in cancer of the uterine cervix. 762 38

A nested case-control study was conducted in Washington County, MD, to determine whether low serum micronutrients are related to the subsequent risk of cervical cancer. Among the 15,161 women who donated blood for future cancer research during a serum collection campaign in 1974, 18 developed invasive cervical cancer and 32 developed carcinoma in situ during the period January 1975 through May 1990. For each of these 50 cases, two matched controls were selected from the same cohort. The frozen sera of the cases and their matched controls were analyzed for a number of nutrients. The mean serum levels of total carotenoids, alpha-carotene, beta-carotene, cryptoxanthin, and lycopene were lower among cases than they were among controls. When examined by tertiles, the risk of cervical cancer was significantly higher among women in the lower tertiles of total carotenoids (odds ratio 2.7; 95% confidence limit, 1.1-6.4), alpha-carotene (odds ratio, 3.1; 95% confidence limit, 1.3-7.6), and beta-carotene (odds ratio, 3.1; 95% confidence limit, 1.2-8.1) as compared to women in the upper tertiles and the trends were statistically significant. Cryptoxanthin was significantly associated with a lower risk of cervical cancer when examined as a continuous variable. Retinol, lutein, alpha- and gamma-tocopherol, and selenium were not related to cervical cancer risk. Smoking was also strongly associated with cervical cancer. These findings are suggestive of a protective role for total carotenoids, alpha-carotene and beta-carotene in cervical carcinogenesis and possibly for cryptoxanthin and lycopene as well.
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PMID:Serum micronutrients and the subsequent risk of cervical cancer in a population-based nested case-control study. 834 56

Human papillomaviruses (HPVs) contribute to the development of benign and malignant cervical cancer; however, the exact role of papillomaviruses in the multistage carcinogenesis process is unclear. The development of HPV-immortalized cervical and foreskin cell lines represents a useful model for studying the role of HPVs in cervical cancer. Studies with these cells show that HPV genes regulate epithelial cell growth and differentiation. Transfection of HPV types associated with invasive cervical cancer results in immortalization of human epithelial cells, whereas HPVs not associated with cancer are ineffective. The combination of E6 and E7 genes, which are normally retained and expressed in cervical carcinomas, is sufficient for immortalization; however, the E7 gene alone induces immortality less efficiently. Although the immortalized cells actively express HPV oncoproteins observed in cervical cancer, after injection of immortal cells into nude mice, tumors are rare, having been reported only for HPV-18. Immortalized cells are resistant to terminal differentiation; in fact, HPVs may contribute to the carcinogenic process by uncoupling the processes of cell growth and differentiation. Host regulation of viral genes also is important in the malignant process. Endogenous cytokines modify HPV gene expression and influence the pathogenesis of HPV infection in the cervix. HPV gene expression is regulated by cellular transcriptional activators and repressors. This normal regulation is altered by viral integration. HPVs become integrated preferentially at chromosomal regions near fragile sites and protooncogenes. In fact, immortality is associated with induction of structural rearrangements frequently affecting HPV integration sites. Structural and numerical alterations nonrandomly involve chromosomes 1, 11, 19, and 20, with chromosome 1 alteration being the most predominant. Wild-type functions of Rb and p53 are necessary to control normal cell growth, and mutation or loss of these suppressor genes often contributes to cancer development. In HPV-containing carcinomas, pRb and p53 were wild type. However, in carcinomas lacking HPV, both suppressor genes were mutated. Functional inactivation of these tumor suppressor genes by HPV oncoproteins E6 and E7 may explain this difference. Treatment of HPV-immortalized cells with ras or a subfragment of herpes simplex virus (HSV) of HPV-immortalized cells resulted in locally invasive carcinomas when the cells were implanted subcutaneously in nude mice. These experiments indicate that HPV integration and expression are insufficient for malignancy but that HPVs do participate in the multistep development of cancer.
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PMID:Cellular and molecular alterations in human epithelial cells transformed by recombinant human papillomavirus DNA. 839 44


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