Barbara McKnight

Human papillomavirus and prognosis of invasive cervical cancer : A population-based study

PURPOSEnTo determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma.nnnPATIENTS AND METHODSnPatients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer-specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models.nnnRESULTSnEighty-six patients had HPV 18-related tumors and 210 patients had HPV 16-related tumors. Cumulative TM among patients with HPV 18-related tumors and among patients with HPV 16-related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16-related cancers, patients with HPV 18-related cancers were at increased risk for TM (HR(TM), 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR(CCSM), 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR(TM), 3.1; 95% CI, 2.3 to 4.2; and HR(CCSM), 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219).nnnCONCLUSIONnHPV 18-related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

Induced abortion and the risk of subsequent ectopic pregnancy

This study assessed the effect of legal induced abortion on ectopic pregnancy risk by using a comparison group of reproductive-age women who were at risk of becoming pregnant during the same time period the women with ectopic pregnancy conceived. Cases were members of Group Health Cooperative of Puget Sound who were hospitalized for ectopic pregnancy from October 1981 through September 1986 (N = 211). Controls were randomly selected members matched to cases on age and county of residence (N = 457). All subjects in this analysis had had one or more prior pregnancies. Eighty-eight cases (41.7 per cent) and 177 controls (38.7 per cent) had a history of one or more induced abortions. The relative risk of ectopic pregnancy associated with one abortion was 0.9 (95 per cent confidence interval 0.6, 1.3), adjusted for age, county, reference date, religion, gravidity, age at first pregnancy, lifetime number of sexual partners, and miscarriage history. Among women with two or more prior pregnancies, the risk associated with two or more abortions was 1.2 (0.6, 2.4). Controlling for pelvic inflammatory disease and use of intrauterine devices did not alter these risks. We conclude that legal abortion as performed in the US since 1970 has little or no influence on a womans risk of ectopic pregnancy in subsequent pregnancies.

The intrauterine device and primary tubal infertility [letter].

The results of a population-based retrospective case-control study published in 1985 on the link between prior use of an IUD and primary tubal infertility have been re-analyzed. The original results set the relative risk of tubal infertility at 2.6 for ever users of an IUD but 6.8 for users of the Dalkon shield. The new calculations eliminated cases of infertility due to abnormalities verified by hysterosalpingography such as bicornuate uterus or uterine polyps; included 15 cases for whom no matched controls with the same matching criteria. The new data set included 487 of 518 potential controls for 161 cases. The new computation yielded a relative risk of 3.7 for ever-use of any IUD 3.9 for ever-use of a copper IUD 6.0 for ever-use of a Dalkon shield and 3.4 for ever-use of any IUD except the Dalkon shield. These results did not change the original interpretation of the study: that while the risks of infertility is heightened after use of the Dalkon shield it is still higher after use of any IUD for nulligravid women.

Multiple primary tumours in women with vulvar neoplasms: a case-control study

We sought to determine whether women with in situ or invasive squamous cell vulvar cancer were more likely than other women to have had a previous or concurrent tumour at other anogenital sites. One hundred and fifty-eight women with vulvar cancer were identified who were first diagnosed during 1980-1985, were ages 18-79 years at that time, and were residents of one of three counties in western Washington. Two control groups were selected: (1) from records of hospital pathology departments, a sample of 113 women with certain benign conditions of the vulva; (2) through random digit dialing, a sample of 212 women from the general population of these counties. Information on a history of other cancers, and on sexual, reproductive, medical, and demographic characteristics was collected from cases and controls in at-home interviews. Cases were more likely to report a history of other anogenital cancers than were controls, with relative risks of 3.5-29.8, depending on the type of case group and type of control. These associations were not explained by case-control differences in demographic characteristics or frequency of cervical screening. On the other hand, prior or concurrent non-anogenital cancers were equally common in cases and controls. These results support the hypothesis that the different anogenital cancers have at least one aetiology in common.

Abstract 5593: Are variants in the syndecan-1 gene associated with breast cancer risk in older women

Syndecans are transmembrane proteins on the cell surface that act as receptors for ligands from a number of protein families. These proteoglycans are involved in a large number of important normal cell functions, including signaling, proliferation, and cell-matrix adhesion; they are also involved in aberrant cell functions such as inflammation, angiogenesis, and carcinogenesis. In a recent pathway directed re-analysis of GWAS data (Menashe, Cancer Research, 2010), variants in the syndecan-1 (SDC1) gene on chromosome 2p were found to be associated with excess risk of breast cancer. We sought to extend this finding by investigating the association between tagging SNPs in the SDC1 gene and risk of breast cancer in our case-control study (The PACE study) in older women. This population-based study includes 845 women who were 65-79 years old at diagnosis of incident breast cancer and 807 age-matched unaffected controls from the Seattle area. The analysis was restricted to Caucasian women. A total of 11 SNPs were chosen to represent 10 bins using Snagger, with double coverage of one large bin. Five SNPs failed genotyping, leaving six SNPs for analysis. At the gene level, a P-min permutation test was not significant for SDC1 (p=0.10). Three SNPs, rs10495704, rs2002090, and rs3771240, were in high linkage disequilibrium in our controls (r2 0.81-0.87) and all three were separately associated with marginally increased risks of breast cancer (OR 1.2, 95% CI 1.0-1.4). One of these SNPs, rs10495704, is in the 5’UTR and thus could be associated with protein processing. No excess risk of breast cancer was associated with the other three SDC1 variants: rs4432408, rs2348478, or rs2015110. A similar pattern of marginally increased risk for the three polymorphisms in high LD (rs10495704, rs2002090, and rs3771240) was found in two subsequent analyses restricted to women with ductal histology and luminal type tumors. We are currently assessing other genes related to inflammation that may be related to breast cancer risk in this study population. The data for SDC1 in the PACE study cannot rule out a modest association with breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5593. doi:10.1158/1538-7445.AM2011-5593

Family History of Breast Cancer as a Modifier of Other Risk Factors

A population-based case-control study was conducted to assess the influence of family history of breast cancer, as a surrogate for the actions of one or more susceptibility alleles, upon the effects of other breast cancer risk factors. Seven hundred thirty-four cases of primary invasive breast cancer diagnosed before age 45 were compared with 938 controls identified through random-digit dialing. The associations of selected risk factors for breast cancer were examined separately among women with no history of breast cancer in their mothers, sisters, aunts, or grandmothers (FH−), and among women with a history of breast cancer in their mothers and/or sisters (FH+). Nulliparity and induced abortion were associated with modestly increased relative risk (RR) estimates among FH- women and larger RR estimates among FH+ women. Our results suggest, at most, modest increases in risk associated with long duration and early age at first use of oral contraceptives (OCs) among FH- women. Among FH+ women, there was an increased risk associated with “ever” use of OCs for one or more years (RR = 1.7), but this was not further influenced by duration or age at first use. While these results require confirmation in other studies, they support the hypothesis that some factors preferentially influence the risk of breast cancer in women genetically predisposed to this disease.