Katherine Mallin

Case-control study of in situ and invasive carcinoma of the vagina

A case-control study of 41 patients with carcinoma in situ (CIS) or invasive cancer of the vagina and 97 community controls was undertaken to identify potential risk factors. Although vaginal and cervical cancers often occur as multiple primaries, only a few common risk factors prevailed. Similar to cervical cancer, low education and family income were risk factors for vaginal CIS and invasive cancer. In addition, history of genital warts was strongly related (RR = 2.9), although other sexual factors were not. Previous genital abnormalities related to subsequent cancer risk, with significant associations seen for vaginal discharge or irritation (RR = 6.1), a previous abnormal Pap smear (RR = 3.8), or an early hysterectomy (RR = 6.7). In addition, there was some evidence that vaginal trauma might be involved, with nonsignificant and independent associations relating to regular douching with preparations other than water or vinegar (RR = 2.7) and frequent washing of the genital area (RR = 2.7). Further studies are needed to determine whether our findings persist among a larger series of cases.

Elevated Serum Homocysteine levels and Increased risk of Invasive Cervical Cancer in US Women

Objectives: To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer. Methods: A large case–control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls. Results: Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (>6.31μmol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p=0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable. Conclusions: Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism.

Cohort mortality study of capacitor manufacturing workers, 1944-2000

A mortality study of workers employed between 1944 and 1977 at an electrical capacitor manufacturing plant where polychlorinated biphenyls (PCBs), chlorinated naphthalenes, and other chemicals were used was undertaken. Age, gender, and calendar year-adjusted standardized mortality ratios (SMRs) were calculated for 2885 white workers. Total mortality and all-cancer mortality were similar to expected in both males and females. Females employed 10 or more years had a significantly elevated SMR of 6.2 for liver/biliary cancer. Intestinal cancer was significantly elevated in females employed 5 or more years after PCBs were introduced (SMR = 2.2). In males, stomach cancer (SMR = 2.2) and thyroid cancer (SMR = 15.2) were significantly elevated. Although individual exposure assessment was limited, PCBs alone or in combination with other chemicals could be associated with increased risks for liver/biliary, stomach, intestinal, and thyroid cancer.

Barrier and spermicidal contraceptive methods and risk of invasive cervical cancer.

The effects of barrier and spermicidal methods of contraception on cervical cancer risk were examined by studying 479 cases of histologically confirmed invasive cervical cancer cases and 788 random digit dialing controls. In addition to a detailed history of contraceptive practices, information was available on numerous potential confounders, including demographic characteristics, sexual behavior, reproductive factors, Pap smear screening history, and smoking. After adjustment for relevant confounders, diaphragm and condom use were found not to be significantly associated with risk of cervical cancer. Although there was a small reduction in risk (OR = 0.8) associated with long-term use (5+ years) of the diaphragm, the effect appeared to relate to concomitant spermicide use, since there was evidence of further decreases in risk for women using spermicides alone for extended periods (OR = 0.7 for 5+ years). Effects were only seen among subjects of higher income and education levels, suggesting that patterns of usage may be important. The potential ability of spermicides to reduce cervical cancer risk by neutralizing viral agents warrants further attention. (Epidemiology 1990; 1:266–272)

Diet and the risk of vulvar cancer

In this case-control study, 201 case patients with vulvar cancer and 342 community control subjects responded to a 61-item food frequency questionnaire. Risk was unrelated to intake of dark green vegetables, citrus fruits, legumes, and vitamins A and C and folate. Risk increased modestly with decreased intake of dark yellow-orange vegetables; the relative risk for the lowest versus the highest quartile was 1.6. Analyses using preliminary determinations of the major carotenoids in common fruits and vegetables suggested that alpha carotene might be the protective constituent in dark yellow-orange vegetables. Intake of beta carotene and provitamin A carotenoids was unrelated to risk. Multivitamin users were at lower risk, compared to nonusers, but no trend was observed with increasing years of use, suggesting that this association was due to unmeasured differences in life-style factors. Risk increased irregularly with the number of cups of coffee consumed per week whereas consumption of alcohol was unrelated to risk.

The fall of zinc protoporphyrin levels in workers treated for chronic lead intoxication

A temporal fall of zinc protoporphyrin (ZPP) levels in whole blood was observed in 51 patients with occupational chronic lead intoxication who were removed from exposure, treated with intravenous calcium disodium edetate (EDTA), and followed for periods up to 2,273 days. ZPP levels fell, with a mean half-life of 68 days, to a mean baseline level of 36 micrograms/dl of whole blood. The baseline ZPP level was positively associated with the length of exposure (p less than .01) and the blood lead half-life (p less than .001). The amount of EDTA received had no apparent effect on ZPP levels. These data suggest that the fall of ZPP levels is largely a function of red blood cell turnover. The baseline ZPP level appears to be a useful biologic index of the biologically active pool of lead for at least two years after removal from exposure.

Serum selenium and the risk of cervical cancer among women in the United States.

Objective: To explore the relationship between serum selenium and cervical cancer. Methods: We conducted a case–control study of cervical cancer in five areas around Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Community controls were selected by random-digit dialing and were matched to invasive cervical cancer cases by age, race/ethnicity, and telephone exchange. Serum selenium was determined by neutron activation analysis. Logistic regression analysis controlling for known risk factors of cervical cancer, including human papillomavirus (HPV) type-16 measured serologically, was performed on 227 invasive cases, 127 in-situ cases, and 526 controls. Results: Values of serum selenium ranged from 67.5 to 185.0 ng/ml. Adjusted odds ratios for invasive cervical cancer by quintile were: 1.0 (highest selenium), 1.1, 1.0, 0.8, and 1.0 (lowest selenium), p for trend = 0.82. Similar patterns were observed for Stage I invasive, and Stages II–IV invasive cases, suggesting severity of disease did not influence the null results. Although no associations were seen among current or never smokers, a protective effect of selenium was suggested among former smokers. Effect modification was not evident for other variables examined. Conclusions: This study does not support a relationship between serum selenium and invasive cervical cancer at typical serum selenium levels in the US.