Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study

Hankinson, S. E.

doi:10.1001/jama.270.23.2813

Cited by 119 publications

(120 citation statements)

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“…Because GALNT1 is known to participate in the glycoslyation of MUC1 (26), and because MUC1 is involved in defense against pathogenic agents, it is tempting to speculate that genetic polymorphisms that encode enzymes involved in glycosylation may reflect interindividual differences to respond to an infectious agent. This may partly explain the observation that tubal ligation is inversely associated with ovarian cancer risk (27)(28)(29)(30). Although this association has been hypothesized to reflect tubal ligation effects on hormonal mechanisms (31) or inflammation (32), the current findings lend some credence to the hypothesis raised by Walhberg (33) of an infectious etiology to ovarian cancer.…”

Section: Discussionsupporting

confidence: 66%

Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

Sellers

Huang

Cunningham³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Studies suggest that underglycosylation of the cell membrane mucin MUC1 may be associated with epithelial ovarian cancer. We identified 26 genes involved in glycosylation and examined 93 single nucleotide polymorphisms (SNP) with a minor allele frequency of z0.05 in relation to incident ovarian cancer. Cases were ascertained at the Mayo Clinic, Rochester, MN (n = 396) or a 48-county region in North Carolina (Duke University; n = 534). Ovarian cancerfree controls (n = 1,037) were frequency matched to the cases on age, race, and residence. Subjects were interviewed to obtain data on risk factors and a sample of blood for DNA and genotyped using the Illumina GoldenGate assay. We excluded subjects and individual SNPs with genotype call rates of <90%. Data were analyzed using logistic regression, with adjustment for age and residence. We fitted dominant, log additive, and recessive genetic models. Among Caucasians, nine SNPs in eight genes were associated with risk at P < 0.05 under at least one genetic model before adjusting for multiple testing. A SNP in GALNT1 (rs17647532) was the only one that remained statistically significant after Bonferroni adjustment for multiple testing but was not statistically significant in Hardy-Weinberg equilibrium among controls. Haplotype analyses revealed a global association of GALNT1 with risk (P = 0.038, under a recessive genetic model), which largely reflected a decreased risk of one haplotype (0.10 frequency; odds ratio, 0.07; P = 0.01) compared with the most common haplotype (0.39 frequency). These results suggest that genetic polymorphisms in the glycoslyation process may be novel risk factors for ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(2):397 -404)

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Section: Discussionsupporting

confidence: 66%

Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

Sellers

Huang

Cunningham³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Studies have recently demonstrated that tubal ligation results in a significant reduction in the subsequent risk of ovarian cancer (Hankinson et al, 1993;Rosenblatt et al, 1996;Green et al, 1997a;Kreiger et al, 1997;Miracle-McMahill et al, 1997). Selective screening for ovarian abnormalities during the procedure cannot account for the striking deficits in risk (40-60%) that have been observed.…”

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confidence: 99%

True

et al. 2000

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SummaryAlthough it has been demonstrated in previous studies that tubal ligation can have widespread effects on ovarian function, including a decrease in the risk of subsequent ovarian cancer, few studies have evaluated effects on breast cancer risk. In a population-based case-control study of breast cancer among women 20-54 years of age conducted in three geographic areas, previous tubal ligations were reported by 25.3% of the 2173 cases and 25.8% of the 1990 controls. Initially it appeared that tubal ligations might impart a slight reduction in risk, particularly among women undergoing the procedure at young ages (< 25 years). However, women were more likely to have had the procedure if they were black, less educated, young when they bore their first child, or multiparous. After accounting for these factors, tubal ligations were unrelated to breast cancer risk (relative risk (RR) = 1.09, 95% confidence interval (CI) 0.9-1.3), with no variation in risk by age at, interval since, or calendar year of the procedure. Subjects were asked to complete a month-by-month calendar documenting all contraceptive methods used since menarche. Pregnancies and other life events were first marked on the calendar to serve as a frame of reference for changes in contraceptive behaviour over time. Information recorded on the calendar regarding the occurrence of a tubal ligation was used to compute the age at, interval since, and calendar time of the procedure.Completed interviews were obtained from 2202 of the 2558 eligible cases (86.1%) and 2009 of the 2477 eligible controls (81.1%). Reasons for non-interview included subject refusals (6.4% in cases vs 14.0% in controls), death (0.4% vs 0.2%), illness (0.6% vs 0.2%), language problems (0.3% vs 1.4%), a move outside of the study area (0.6% vs 2.3%) and other miscellaneous reasons (0.2% vs 0.8%). In addition, physician consent for interview was denied for 5.4% of the cases. Among controls, an overall response rate of 73.4% was achieved through multiplication of the telephone screener and interview response rates. To assure comparability between the cases and controls, the 29 cases who indicated on interview that they did not have a residential telephone and the 19 controls with a history of breast cancer were eliminated, leaving 2173 cases and 1990 controls available for analysis.Since the median interval between diagnosis and interview was 87 days for cases, all information on risk factors, including that pertaining to tubal ligations, was truncated at the date of diagnosis for cases or the date at completion of the telephone screener for controls. The relationship of breast cancer risk factors to tubal ligation among the controls was assessed by calculating χ 2 statistics. The relationship of tubal ligation to breast cancer risk was assessed through calculation of odds ratios to approximate relative risks (RRs). Logistic regression analyses were used to obtain maximum likelihood estimates of RRs and their 95% confidence intervals (CI) (Breslow and Day, 1980). The significance of in...

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“…1,6 Some epidemiological studies demonstrated a lower risk for ovarian clear cell carcinomas and endometrioid ovarian carcinomas after tubal ligation or hysterectomy. [30][31][32] A recent proposition for an ovarian cancer risk-assessment tool integrated endometriosis as well as no tubal ligation each as one of totally eight conditions associated with ovarian cancer. 33 ARID1A mutations are supposed to have a key role in the formation of endometriosis-associated ovarian carcinomas and are probably occurring early, already at the stage of endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?

Samartzis

Noske

et al. 2012

Modern Pathology

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Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n ¼ 136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n ¼ 3/20, 15%) and one deep-infiltrating endometriosis sample (n ¼ 1/22, 5%), but in none of the peritoneal endometriosis (n ¼ 0/16) and eutopic endometrium samples (n ¼ 0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (Po0.0005), as well as peritoneal (P ¼ 0.003) and deep-infiltrating endometriosis (P ¼ 0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.

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Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study

Cited by 119 publications

References 0 publications

Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

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Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?

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