Larry McGowan

A case-control study of epithelial ovarian cancer

With data from a study of 296 patients with primary epithelial ovarian cancer and 343 patients hospitalized because of other conditions, we estimated ovarian cancer risk in accordance with reproductive and other factors. Risk was greatest among women of lower parity, especially among women who said they planned to have children but could not. The protective effect of oral contraceptives seen in other studies was observed only in subgroups of our study population. Women who had breastfed their children had decreased risk, but the number of months of breastfeeding was not related to risk. Incomplete pregnancies did not provide the protection seen for live births. A family history of ovarian cancer and a medical history of breast cancer were both strong risk factors. None of the nonreproductive factors that we examined, including childhood illnesses, tobacco and alcohol consumption, obesity, and selected adult diseases, was convincingly associated with risk.

The woman at risk for developing ovarian cancer

Abstract Defining the woman at risk for developing ovarian cancer can identify factors that cause the disease and lead to earlier diagnosis and improved survival. Our 3-year case-control study of 197 women with histologic proven primary ovarian cancer of the epithelial type reveals the typical patient to have a family history of gynecologic cancer, be exposed to rubella in the peripubertal period, be nulliparous or of low parity, experience difficulty in conceiving, have certain exacerbated premenstrual symptoms, and to rarely undergo surgically induced menopause. In women with carcinomas of low malignant potential a later onset of menarche as well as menstrual disorders occur.

p53 polymorphism and risk of cervical cancer

Storey and co-workers have reported data suggesting that individuals homozygous for arginine at residue 72 of p53 (p53Arg) are about seven times more susceptible to invasive cervical cancer than individuals who carry at least one proline at that position (p53Pro). These preliminary data were supported by in vitro evidence demonstrating that the E6 oncoprotein of human papilloma virus (HPV) degrades p53Arg more efficiently than p53Pro. We have now tested specimens from a total of 1,309 women in three studies for p53 polymorphisms. We find that p53Arg is not associated with an increased risk of preinvasive or invasive cervical neoplasia; indeed, there is a tendency for p53Arg to be associated with a decreased risk of neoplasia.

Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix

Hormonal factors may play a more prominent role in cervical adenocarcinoma than squamous cell carcinoma. The authors evaluated whether obesity, which can influence hormone levels, was associated with adenocarcinoma and squamous cell carcinoma.

Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States)

AbstractObjectives: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. Methods: This multicenter case–control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. Results: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3–1.1; ≥1 pack per day: OR = 0.7, 95% CI 0.4–1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9–2.9; ≥1 pack per day: OR = 1.8, 95% CI 1.0–3.3). Results in analyses restricted to HPV-positive controls were similar. Conclusion: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Comprehensive analysis of human leukocyte antigen class I alleles and cervical neoplasia in 3 epidemiologic studies.

To comprehensively explore the relationship between human leukocyte antigen (HLA) class I alleles and cervical neoplasia, a subset of participants from 3 large US and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects were women with cervical cancer or high-grade squamous epithelial lesions (HSILs; n=365) or low-grade squamous epithelial lesions (LSILs; n=275) or who were cytologically normal (control subjects; n=681). Allele-disease associations were assessed by logistic regression analysis. Consistent associations across all studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95% confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37-1.04) for LSILs, compared with control subjects and adjusted for study. This finding supports the hypothesis that a single allele may be sufficient to confer protection against cervical neoplasia. Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia.

Microinvasion in low malignant potential tumors of the ovary

The presence of microinvasion (Mi) has not previously been investigated in nonserous low malignant potential (LMP) tumors of the ovary. In serous LMP tumors (SLMP), Mi has not worsened the prognosis compared with usual SLMP in previous reports. In a retrospective clinicopathologic review of 126 cases of serous and mucinous LMP (MLMP) tumors of the ovary, the authors identified 14 cases with Mi: seven of 72 SLMP, four of 44 mucinous intestinal LMP (MILMP), and three of 10 mucinous müllerian LMP (MMLMP). Tumors with Mi resembled usual LMP histologically except for small foci (up to 0.2 cm) in the stroma consisting predominantly of single cells or small clusters of cells, sometimes in a cribriform pattern. In SLMP-Mi, the cells had eosinophilic cytoplasm, and the stromal reaction was minimal/absent. In MILMP-Mi and MMLMP-Mi, nuclear staining was paler; the stroma often showed a fibrous reaction or edema, especially in MILMP-Mi. All 14 patients had follow-up (2.2 to 18.6 years) and were without evidence of disease. Careful screening of both mucinous and serous ovarian LMP can show Mi. Mi foci should be distinguished from true stromal invasion, pseudoinvasion, endothelial cells, decidual cells and histiocytes, and pseudomyxoma in mucinous LMP. Mi does not seem to worsen prognosis in MLMP and SLMP tumors of the ovary.

Characteristics Relating to Ovarian Cancer Risk: Collaborative Analysis of 12 U.S. Case-Control Studies. VI. Nonepithelial Cancers among Adults

Nonepithelial ovarian cancers are rare, and little is known about their etiology. Of particular interest are the effects of oral contraceptive use and pregnancy, both of which are associated with large decreases in risk for epithelial ovarian cancer. We examined the risk factors for nonepithelial ovarian tumors by combining data from four case-control studies conducted in the United States. We compared personal characteristics of 38 germ cell cases and 45 stromal cases, respectively, with 1,142 and 2,617 general population controls. All subjects were over age 18 years. For germ cell tumors, there was a weak negative association with parity but no consistent pattern of decreasing risk with increasing parity. In contrast, relative to nulligravid women, gravid nulliparous women were at increased risk of developing a germ cell cancer [odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.2-18.61. The use of oral contraceptives was also associated with elevated risk (OR = 2.0,95% CI = 0.77- 5.1); however, no clear trends in risk were observed. For stromal tumors, oral contraceptive use was associated with decreased risk (OR = 0.37, 95% CI = 0.16-0.83), whereas pregnancy was associated with a small elevation in risk. A trend of increasing risk with increasing age at first term pregnancy was observed, with an odds ratio of 3.6 (95% CI = 1.0-12.5) for a first birth after age 29 years. Risk factors for nonepithelial ovarian cancers do not appear to parallel each other or those for epithelial ovarian cancer. (Epidemiology 1992;3:490-495)

The biochemical diagnosis of ovarian cancer

Abstract Ovarian cancer has the second highest average annual increase of deaths caused by cancer in American women and an over-all 30 per cent 5 year survival rate. In an attempt to find a new diagnostic aid for ovarian cancer, peritoneal fluid and blood specimens were obtained from normal women and from women with benign and malignant neoplastic ovarian tumors. A diagnostic biochemical pattern for ovarian cancer has been established with the use of a small quantity of peritoneal fluid and analysis by the sequential multiple analyzer 12/60. Calcium, inorganic phosphorus, urea nitrogen, uric acid, cholesterol, total protein, total bilirubin, lactic dehydrogenase, and glutamicoxaloacetic acid transaminase levels were elevated above the values found in control women. The results suggest that the biochemical pattern of peritoneal fluid may be used to distinguish benign from malignant neoplastic ovarian tumors, to discover earlier residual or recurrent ovarian cancer, to allow therapy to be started sooner, to monitor therapy, and perhaps to screen normal women for ovarian cancer.

Cytologic methods for the detection of endometrial cancer.

Abstract The use of a small-diameter, flexible endometrial cannula for aspirating endometrial cells is the most simple, safe, inexpensive, and reliable method for physicians to use in their offices to routinely screen asymptomatic women at high risk for endometrial cancer. Earlier detection of endometrial cancer will improve patient survival and the direct endometrial aspiration cytologic smear will enhance that goal.