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A case-control study was conducted to examine the relationship between Wilms' tumor and paternal occupational exposures. The case group consisted of 200 children diagnosed as having Wilms' tumor who were registered at selected National Wilms' Tumor Study institutions during the period June 1, 1984, to May 31, 1986. Disease-free controls were matched to each case using a random digit dialing procedure. The parents of cases and controls completed a self-administered questionnaire. There was no consistent pattern of increased risk for paternal occupational exposure to hydrocarbons or lead found in this study. However, certain paternal occupations were found to have an elevated odds ratio (OR) of Wilms' tumor, including vehicle mechanics, auto body repairmen, and welders. Offspring of fathers who were auto mechanics had a 4- to 7-fold increased risk of Wilms' tumor for all 3 time periods. The largest increased odds ratio for auto mechanics was in the preconception period [OR = 7.58; 95% confidence interval (CI) = 0.90-63.9]. Welders had a 4- to 8-fold increased odds ratio, with the strongest association during pregnancy (OR = 8.22; CI = 0.95-71.3). Although chance cannot be excluded as a possible explanation, association of Wilms' tumor with these occupations has been reported in previous studies. Further study is needed to provide data on the specific occupational exposures involved.

A population-based case-control study was conducted to examine the relationship between maternal smoking and the occurrence of abruptio placentae and to assess the joint relationship of smoking and small for gestational age (SGA) status with abruption. Cases (N = 1089) reported on Washington state birth certificates from 1984-1986 were compared with randomly selected births (N = 2323) from the same period. The occurrence of placental abruption was associated with both smoking (relative risk = 1.6; 95% confidence interval 1.3-1.8) and SGA status (relative risk = 2.6; 95% confidence interval 2.0-3.3). The association with SGA status was identical for smokers and non-smokers. Thus, the increase of SGA infants in women whose pregnancies are complicated by abruption is not explained by maternal smoking, and in some cases may result from placental dysfunction induced by the process of placental separation.

Electric blankets are an important domestic source of electromagnetic fields (EMF) because of the relatively high intensity of emission, prolonged exposure, and intimate contact with the source. In a case-control study of testicular cancer in western Washington during 1981 to 1984, the relation between EMF exposure from electric blankets and the occurrence of testicular cancer was examined. The respective proportions of cases and controls who reported the use of an electric blanket were almost identical (age-adjusted rate ratio (RR) = 1.0, 95% confidence interval (CI) 0.7-1.4). Distributions of the duration of use were also very similar in cases and controls. Compared with controls, the frequency of use of an electric blanket was slightly lower in men with seminoma (RR = 0.7, 95% CI 0.5-1.2) and slightly higher among men with nonseminoma germ cell tumors (RR = 1.4, 95% CI 0.9-2.3). Overall, the results of this study suggest that increased exposure to EMF from electric blankets contributes little, if at all, to the risk of testicular cancer in adult white men.

Recreational drug (marijuana, lysergic acid diethylamide or LSD, speed, cocaine, and "other") exposures of women with primary infertility were compared with those of a matched control group of women with proven fertility. Women who reported smoking marijuana had a slightly elevated risk for infertility due to an ovulatory abnormality (RR = 1.7, 95% CI = 1.0 to 3.0). The risk was greatest among women who had used marijuana within one year of trying to become pregnant (RR = 2.1, 95% CI = 1.1 to 4.0). No consistent frequency or duration of use effects could be demonstrated, and the risk was confined to low-frequency users. Risks associated with the use of other drugs were not elevated. The risk of infertility from a tubal abnormality associated with cocaine use was greatly increased (RR = 11.1, 95% CI = 1.7 to 70.8). Our results are consistent with animal studies suggesting that smoking marijuana may cause a transient disruption of ovulatory function. The possibility that cocaine exposure influences the development of tubal infertility needs further investigation.

We conducted a population-based case-control study to assess the association between maternal smoking during pregnancy and the risk of giving birth to a child with a congenital malformation. Cases were all singleton livebirths with a congenital malformation recorded on the 1984-1986 Washington State Birth Records (n = 3284). The smoking histories of these mothers were compared to a randomly selected group of mothers with a singleton livebirth of a child without a malformation during these same years (n = 4500). When all malformations were taken as a group, there was no association with maternal smoking (relative risk (RR) = 1.0, 95% CI 0.9-1.1). However, increased risks were observed for a number of specific malformations, including microcephalus (RR = 2.0, 95% CI 1.0-4.0), cleft defects (RR = 1.4, 95% CI 1.0-2.0), and club foot (RR = 1.4, 95% CI 1.0-2.0). We did not find any association with Down's syndrome (RR = 0.8 95% CI 0.5-1.3) or any other malformation. We conclude that maternal smoking during pregnancy may be associated with an increased risk for some malformations.

In a prospective study of morbidity associated with Chlamydia trachomatis infections during pregnancy, we isolated C trachomatis from the endocervix of 18 (6.7%) of 268 women examined before 19 weeks' gestation. Infected women were significantly younger than noninfected women, and significantly more often unmarried, supported by public assistance, and pregnant for the first time. Among women followed up from 19 weeks' gestation until delivery, the mean duration of gestation was significantly shorter for those with antepartum chlamydial infection. Stillbirth or neonatal death occurred in six (33%) of the 18 pregnancies of infected women compared with eight (3.4%) of the 238 pregnancies of noninfected women followed up from the 19th week of gestation through delivery. Stillbirth or neonatal death occurred ten times more often among Chlamydia-infected women than among uninfected controls matched for age, marital status, socioeconomic status, pregnancy order, and race.

As part of a case-control study of tubal pregnancy, we sought to evaluate the potential etiologic role of maternal cigarette smoking. Between 1975-1979, 192 women who were treated for a tubal pregnancy in five Seattle hospitals were interviewed with regard to smoking habits and reproductive, contraceptive, and medical histories. For comparison, 459 Seattle-area women who delivered during the same period were also interviewed. Current cigarette smokers had a more than twofold increase in risk of tubal pregnancy (adjusted relative risk 2.2; 95% confidence interval 1.4-3.4) when compared with women who had never smoked. The risk for women who had stopped smoking before conception was 1.6 (95% confidence interval 1.0-2.8). There was no consistent trend between the risk of tubal pregnancy and the duration of smoking, average number of cigarettes smoked per day, age at which a woman began to smoke, pack-years of cigarettes smoked, or (among former smokers) the recency of smoking. Although several sources of bias in the present study may have created a spurious association between cigarette smoking and the occurrence of tubal pregnancy, it could well be that an increased risk of tubal pregnancy is yet another untoward consequence of cigarette smoking.

Women who were hospitalized for tubal pregnancy in five hospitals in King County, Washington, between 1975 and 1979 were interviewed regarding a prior history of gonorrhea, genital herpes, genital warts and trichomoniasis. Their responses were compared to those of women who delivered a live-born child during the same period. Multiple logistic regression was used to control for the effects of race, gravidity, smoking, Dalkon Shield use, douching, number of sexual partners and history of additional sexually transmitted diseases. The risk of tubal pregnancy in women who reported a history of gonorrhea, relative to that in other women, was 5.1. As compared to controls, women with tubal pregnancy more often reported a history of genital herpes and a history of trichomoniasis.

Female residents of six counties in Washington and Utah in whom a diagnosis of ovarian cancer was made during 1975-79 were interviewed concerning prior use of oral contraceptives. Interviews with a random sample of women drawn from these same counties were obtained for comparison. A smaller proportion of women with epithelial ovarian tumors had taken oral contraceptives than had controls: the estimated risk of ovarian cancer in uses relative to that in non-users was 0.57 (p = 0.04). The magnitude of the decreased risk depended on the duration over which oral contraceptives had been taken, as the negative association was present only after 4 or more years of use. In many ways, the use of oral contraceptives mimics the physiologic effects of pregnancy. The results of the present investigation, when interpreted together with those from other epidemiologic studies and from experiments in animals, suggest that, like pregnancy, the use of oral contraceptives has a protective effect against the development of ovarian cancer.

The relationship of weight at birth to the occurrence of childhood cancer was studied with emphasis on the influence of age at diagnosis. Birth certificates for 681 children with cancer born in Washington State were linked with cancer registry data. Among children diagnosed with cancer during the first several years of life, there was an increased proportion with a high birth weight (greater than 4,000 g). The relationship was strongest for children under 2 years of age; about twice as many of them had high birth weights. However, the relationship was not present at all in those whose cancer was diagnosed at age 4 or older. This excess risk in young children associated with high birth weight was distributed among several types of cancer, including the two most common ones (leukemia and neuroblastoma).

A specially designed method for measuring infant mortality among families with subsequent siblings of sudden infant death syndrome (SIDS) victims in the state of Washington, 1969 to 1984, yielded results similar to those from an earlier study in Norway. In both studies the SIDS rates among siblings were substantially lower than prior estimates. The rate of SIDS in siblings of infants who died of SIDS did not differ significantly from the SIDS rate among control infants matched for maternal age and birth order. Total infant mortality rates in the two groups were virtually identical. From the data at hand, it appears that earlier estimates of the risk of SIDS in siblings were inflated and that parents of SIDS victims can be counseled accordingly.

We studied the importance of a history of appendectomy for appendicitis in 279 women with laparoscopically or surgically diagnosed tubal infertility and a control group of 957 fertile women. After controlling for the effects of age, use of an intrauterine device for contraception, a history of pelvic inflammatory disease, and other potential confounding variables, we found that no excess risk of tubal infertility was associated with a simple appendectomy without rupture. However, when the operation was reportedly for a ruptured appendix, the relative risk of tubal infertility was 4.8 (95 percent confidence interval, 1.5 to 14.9) for women who had never been pregnant and 3.2 (95 percent confidence interval, 1.1 to 9.6) for women with one or more previous pregnancies. We conclude that the early diagnosis and treatment of suspected appendicitis in girls and women of reproductive age may reduce the incidence of tubal infertility resulting from the sequelae of a ruptured appendix.

A case-control investigation was conducted to evaluate the hypothesis that past exposure to the pesticide lead arsenate led to an excess mortality from respiratory cancer. Cases included all white male orchardists who died in Washington State between 1968 and 1980 from respiratory cancer. Orchardists who died of other causes during this period served as controls. Occupational and smoking data for 155 case subjects and 155 control subjects were obtained via telephone interview with next-of-kin/informants. Neither presence, intensity, nor duration of lead arsenate exposure differed between case and control subjects. Although cigarette smoking was unusually common among cases of respiratory cancer, smoking habits of the orchardists and a sample of non-orchardists who had died of other causes were quite similar. The cause of the excess mortality from respiratory cancer among Washington State orchardists remains unknown.

The relationship between the occurrence of female breast cancer and menopausal estrogen replacement was investigated in a population-based case-control study. One hundred and eighty-three white female residents of King County, Washington (ages 50-74) in whom breast cancer was diagnosed from July, 1977, through August, 1978, were interviewed with respect to reproductive and other factors, with emphasis on the use of estrogen-containing medication. For purposes of comparison, the same data were collected from 531 white female King County residents of the same ages without breast cancer. Use of menopausal estrogens was reported somewhat more commonly among controls than among cases (relative risk = 0.74, 95% confidence interval = 0.51-1.08) and some variation in proportions of users was present between different hysterectomy-oophorectomy subgroups. However, each of these differences could easily have been due to chance. No substantial trends in risk were apparent with increasing duration of use, time since first use, time since last use, or average dose. The findings suggest that in King County no important relationship exists between use of menopausal estrogens and the occurrence of breast cancer.

One hundred twenty-seven women who had been given diagnoses of tubal infertility between 1979 and 1981 in King County, Washington, yet previously had been pregnant, were interviewed to determine their prior history of legally induced abortion. Their responses were compared with those of 395 women who conceived a child at the same time the infertile women began their unsuccessful attempt to become pregnant. In making the comparison, we adjusted for the effects of variables that in this population were related both to having an induced abortion and to the occurrence of infertility, i.e., age, number of prior pregnancies, number of sexual partners, cigarette smoking habits, Dalkon Shield (A. H. Robins Company, Richmond, VA) use, and whether the woman worked outside the home. The risk of tubal infertility in women who had had an induced abortion was not increased above that of other women (relative risk, 1.15; 95% confidence interval, 0.70 to 1.89). For women with two or more abortions, the relative risk was 1.29 (95% confidence interval, 0.39 to 4.20). When only the most recent pregnancy was considered, the relative risk was 1.19 (95% confidence interval, 0.72 to 1.97). Our results suggest that legal abortion, as performed during the past decade in the United States, does not carry an excess risk for future tubal infertility.

Data from a case-control study of childhood brain tumors were analyzed to examine the possibility that paternal occupation in the aerospace industry is related to the development of a brain tumor in offspring. Parents of 51 children with brain tumors diagnosed in western Washington State during 1978-81 were interviewed, and their responses were compared to those of parents of 142 children selected at random from this population. Among all children, proportions of case and control fathers who had ever been employed in the aerospace industry were nearly identical [relative risk (RR) = 0.94; 95% confidence interval (CI) = 0.40-2.19]. Employment in the aerospace industry during the period from 1 year prior to birth to the time of diagnosis and any employment in the manufacturing part of the industry were not associated with increased risk. However, stratification by age at diagnosis revealed an increased risk associated with father's ever-employment in the industry (RR = 2.10; 95% CI = 0.79-5.60) for children under 10 years old. A corresponding decreased risk (RR = 0.12; 95% CI = 0.01-1.08) was found for children over 10 years old. Because of the relatively small number of cases with a positive paternal occupational history, interpretations of the difference in the direction of the association according to age at diagnosis must remain tentative ones.

Fifty-seven female residents of King and Pierce Counties (Washington State) with a new diagnosis of in situ or invasive vulvar carcinoma during 1976-79 were interviewed concerning their menstrual, reproductive, and medical histories. A random sample of women residing in the same area was interviewed for comparison. A greater proportion of women with in situ vulvar tumors than control subjects were of low educational level, reported a history of oral contraceptive use, experienced early age at first birth, late age at menopause, and were current or former cigarette smokers. Menstrual and reproductive factors were similar between women with invasive vulvar cancer and controls, but a greater proportion of cases reported a history of diabetes and of cigarette smoking. The factors found in this study to be associated with in situ vulvar carcinoma are similar to those observed among women with cervical cancer. In addition, since the vulva and cervix both are derived from cloacal tissue, and neoplasms of the two sites occur together more often than would be expected by chance, in situ vulvar and cervical tumors may share some common etiologies.

The possibility that intrascrotal temperature is involved in the etiology of testicular cancer was investigated through a population-based case-control study conducted in western Washington State. A total of 323 men with germ cell tumors of the testis diagnosed between 1977 and 1984 and 658 randomly selected controls were interviewed with regard to type of shorts worn, use of long underwear, heat-resistant clothing, and hot tubs or saunas, and a history of varicocele. No association was found between testicular cancer and having worn tight-fitting underwear (jockey shorts) or having worn heat-resistant clothing on the job. A 50% increase in risk was observed for men who typically wore long underwear for more than three months out of the year, but this association was within the limits of chance given no true association. A smaller fraction of the men with cancer than controls had used a hot tub or sauna in the preceding five years, but the size of the case-control difference was not related to the frequency of use. The relative risk associated with a history of physician-diagnosed varicocele was 1.8 (95% confidence interval 0.9-3.4). There was little difference between men with seminomas and those with other germ cell tumors regarding any of the above exposures. Taken in aggregate, these results provide little or no support for the hypothesis that intermittent intrascrotal temperature elevation, to the degree encountered by US men today, plays a role in the etiology of germ cell testicular cancer. The possibility that risk increases after a continuous temperature increase, such as might result from a varicocele, needs to be evaluated further.

Previous studies of the effect of mother's employment on infant birth weight have shown mixed results. This study was designed to explore the relationship between activity level of a woman's occupation and her risk of delivering a low-birth-weight infant. Using 1981 state of Washington birth certificate records, the authors selected 5,822 subjects. Case subjects were women who had delivered infants weighing 2,500 g or less; controls were those who had delivered normal-weight infants. Women were grouped into five activity levels based on their usual occupation. No association was detected between activity level of mother's usual occupation and delivery of a low-birth-weight infant. These data suggest that active work is not associated with an increased risk of having a low-birth-weight baby.

The relationship of acute urinary tract infection occurring during pregnancy and the incidence of adverse fetal outcomes was examined with the use of birth certificate data from Washington state for the years 1980 and 1981. The two-year fetal mortality rate among urinary tract infection-associated pregnancies was found to be 17.9 per thousand livebirths, 2.4 times the rate for the state as a whole. Low birth weight newborns and small for gestational age newborns were, respectively, 2.04 and 1.57 times more frequent in urinary tract infection-associated pregnancies compared to controls. These estimates of risk were unchanged when adjusted for maternal age, race, and past obstetric history. The risk of prematurity in women with urinary tract infection and no history of fetal loss was 2.4 times the control risk. Sepsis was rare in both the urinary tract infection and control groups. These results add to the evidence implicating maternal urinary tract infection as a threat to fetal well-being.

The incidence data from nine population-based cancer registries participating in the Surveillance, Epidemiology and End Results program in the U.S. suggest that squamous cell carcinoma arising from different parts of the larynx have different etiologic influences. The male to female rate ratio for laryngeal cancers was substantially higher in the glottic region (9.2 among whites and 11.8 among blacks) than in other subsites (approx. 3-5 in both races). The sex rate ratios were uniformly higher for glottic tumors in all age groups, and these ratios increased more rapidly with age for glottic than for supraglottic tumors. Factors that are closely related to sex other than smoking and drinking behavior are responsible for the considerably high ratio of male to female rates of the glottic tumors. Future etiologic studies should investigate the possible differential effect of hormonal or other sex-related factors on different anatomic subsites within the larynx.

Women who use an intrauterine device (IUD) are at increased risk of acute pelvic inflammatory disease, but the relation of the IUD to subsequent infertility is not established. We interviewed 159 nulligravid women with tubal infertility to determine their prior use of an IUD. Their responses were compared with those of a matched group who conceived their first child at the time the infertile women started trying to become pregnant. The risk of primary tubal infertility in women who had ever used an IUD was 2.6 times that in women who had never used one (95 per cent confidence interval, 1.3 to 5.2). The observed difference between cases and controls was not uniform for different types of IUD. The relative risk associated with use of a Dalkon Shield was 6.8 (1.8 to 25.2), and that associated with use of either a Lippes Loop or Saf-T Coil IUD was 3.2 (0.9 to 12.0). The smallest elevation in risk was found among users of copper-containing IUDs (relative risk, 1.9 [0.9 to 4.0] for all women who had ever used a copper-containing IUD). The relative risk for women who used only a copper-containing IUD was 1.3 (0.6 to 3.0). We conclude that use of the Dalkon Shield (and possibly of plastic IUDs other than those that contain copper) can lead to infertility in nulligravid women.

We have examined the distribution of human papillomavirus (HPV) DNA in paraffin sections of humans warts by in situ hybridization with biotin-labeled DNA probes. Recombinant plasmid DNAs (HPV-1, -6, -11, -16) were labeled by nick translation with biotinylated deoxyuridine triphosphate. Paraffin sections were hybridized with the probes for 18 h in stringent or non-stringent conditions, and DNA-DNA hybrids were detected by immunocytochemistry. Paraffin sections of warts were also examined for the presence of HPV capsid antigen with the avidin-biotin peroxidase complex method for immunocytochemistry. HPV DNA was detected and localized in paraffin sections from a plantar wart, a laryngeal papilloma, and seven anogenital condylomas. The specific HPV type present in each lesion was determined by hybridization under stringent conditions with the homologous DNA probe. The papillomas were found to contain many more cells with replicating virus DNA, as demonstrated by in situ hybridization, than was apparent from the number of cells containing detectable virus antigen. In situ hybridization with biotin-labeled probes is an effective technique for the identification of HPV infection in routinely collected and processed tissue specimens.

To clarify the nature of the association between respiratory distress syndrome and Cesarean section birth, a study was conducted which compared 273 premature (36 weeks or less) Cesarean-delivered infants with 341 premature vaginally delivered infants who were born at the University of Washington Hospital from January 1, 1977 through March 31, 1980. The gestational age-adjusted probability of respiratory distress syndrome was higher among the Cesarean cohort compared with the vaginal cohort (38.2% vs. 27.6%, odds ratio = 1.63, 95% confidence interval = 1.11-2.39). Three alternative explanations for the association of Cesarean section with respiratory distress syndrome other than causation were tested, and each was rejected. The association was not explained by 1) improper timing of elective Cesarean deliveries; 2) misclassification of cases of mild, transient respiratory distress (which may be more common after Cesarean birth) as respiratory distress syndrome; or 3) the differences in the occurrence of pregnancy complications preceding Cesarean births compared with vaginal births. Lack of labor appears to account for part of the increased risk of respiratory distress syndrome among infants delivered by Cesarean section. The gestational age-adjusted probabilities of respiratory distress syndrome were 47.0% for Cesarean birth without labor, 35.4% for Cesarean birth preceded by labor, and 27.6% for vaginal birth.

Women who were hospitalized for ectopic pregnancy in five hospitals in King County, Washington, were interviewed concerning history of induced abortion. For comparison, women who delivered a live-born child during this same time period were also interviewed. Relative to women who had never undergone an abortion, the risk in those who had was increased to a modest degree, but this increase could well have been the result of chance (relative risk, 1.4; 95% confidence interval, 0.7 to 2.6). For women who had two or more abortions, the relative risk was 1.8 (95% confidence interval, 0.5 to 7.1). Our results suggest that legal abortion as performed during the past decade in the United States does not carry a large excess risk for future ectopic pregnancy, but larger studies will be needed in order to determine more precisely the magnitude of any excess that does exist.

To elucidate the risk factors for anal cancer, we interviewed and obtained blood specimens from 148 persons with anal cancer and from 166 controls with colon cancer in whom these diseases were diagnosed during 1978-1985. We found that in men, a history of receptive anal intercourse (related to homosexual behavior) was strongly associated with the occurrence of anal cancer (relative risk, 33.1; 95 percent confidence interval, 4.0 to 272.1). Anal intercourse was only weakly associated with the risk of anal cancer in women (relative risk, 1.8; 95 percent confidence interval, 0.7 to 4.2). Among the subjects with squamous-cell anal cancer, 47.1 percent of homosexual men, 28.6 percent of heterosexual men, and 28.3 percent of women gave a history of genital warts, as compared with only 1 to 2 percent of controls and no patients with transitional-cell anal cancer. In patients without a history of warts, anal cancer was associated with a history of gonorrhea in heterosexual men (relative risk, 17.2; 95 percent confidence interval, 2.0 to 149.4) and with seropositivity for herpes simplex type 2 (relative risk, 4.1; 95 percent confidence interval, 1.9 to 8.8) and Chlamydia trachomatis (relative risk, 2.3; 95 percent confidence interval, 1.1 to 4.8) in women. Current cigarette smoking was a substantial risk factor in both women (relative risk, 7.7; 95 percent confidence interval, 3.5 to 17.2) and men (relative risk, 9.4; 95 percent confidence interval, 2.3 to 38.5). We conclude that homosexual behavior in men is a risk factor for anal cancer, and that squamous-cell anal cancer is also associated with a history of genital warts, an association suggesting that papillomavirus infection is a cause of anal cancer. Certain other genital infections and cigarette smoking are also associated with anal cancer.

We investigated the relationship of route of delivery and of antepartum Chlamydia trachomatis cervical infection to selected forms of puerperal infectious morbidity, including intrapartum fever, or early (less than 48 hours) postpartum fever not attributable to infections of sites outside the uterus and late (48 hours to 6 weeks) postpartum endometritis. Infectious morbidity occurred in 27 (44%) of 62 women who underwent cesarean section and in 33 (10%) of 329 who underwent vaginal delivery (p less than 0.001). Postsection infectious morbidity was not correlated with C. trachomatis infection and was largely limited to early postpartum fever. Among women who underwent vaginal delivery, infectious morbidity occurred in 10 (34%) of 29 women with and in 23 (8%) of 300 without C. trachomatis infection (p less than 0.001), and chlamydial infection was associated only with intrapartum fever and late postpartum endometritis. Separate matched case-control analyses confirmed that cesarean section was associated with an increased risk of early postpartum fever (p = 4 x 10(-8)); whereas among women who underwent vaginal delivery, antepartum C trachomatis infection was associated with an increased risk of development of intrapartum fever or late postpartum endometritis (p = 0.002).

We studied the effect of induced abortion on outcome of subsequent pregnancy in a sample of 4896 parturients in Seattle, Washington, from July, 1972, through June, 1976. We used a matched-pair analysis for 571 women with histories of prior abortions. In addition to analyses involving all women with histories of induced abortions, separate analyses were done for 97 black women and 277 primiparas. Histories of prior induced abortions were not related to low birth weight, premature delivery, stillbirth, neonatal death, miscarriage or congenital malformations in subsequent pregnancies. The termination procedure and weeks of gestation at time of termination were not related to the later occurrence of low birth weight or premature delivery.

The incidence of ectopic pregnancy in the United States has more than doubled in the past decade. Because a previous study has suggested that the practice of vaginal douching may increase the risk of pelvic inflammatory disease, a condition known to predispose to ectopic pregnancy, and because the sale of commercial douching products in the United States has more than tripled since 1974, we investigated this practice as a possible risk factor. We interviewed 155 women who had a tubal ectopic pregnancy treated at five Seattle hospitals between 1975 and 1979 as to their reproductive, contraceptive, and medical histories, demographic characteristics, and personal hygiene practices. During the same period, 456 women who were delivered of a baby in King County were identified from Vital Records and interviewed as controls. A higher proportion of cases than controls reported ever having douched in the past. Cases also douched more frequently than controls. After simultaneous adjusting for confounding factors in our data by means of a multiple logistic regression technique, the risk of tubal ectopic pregnancy for women who douched at least weekly was twice that of women who never douched (95% confidence interval = 1.03 to 4.00). The risk for women who used commercial douches on a weekly basis was 4.4 (95% confidence interval = 1.6 to 12.7) the risk for women who never douched.

One hundred forty-nine patients who underwent surgery for tubal pregnancy at five hospitals in Seattle (WA) between 1975 and 1979 were interviewed to determine the risk factors for this disorder. Their responses were compared with those of 706 control women who had conceived an intrauterine pregnancy during the same time period during which the tubal pregnancies occurred. A higher proportion of cases reported a history of infertility (attempt to conceive without success for a period of at least 1 year) than controls (relative risk [RR] = 2.5; 95% confidence interval [CI] = 1.7-3.7). Women who were diagnosed in the investigation of their infertility as having tubal or ovulatory dysfunction had relative risks of tubal pregnancy of 5.8 (95% CI = 2.1-16.4) and 3.4 (95% CI = 1.3-8.5), respectively. The average time over which subjects had attempted to conceive before index pregnancies that were planned was longer among cases (15.4 months) than among controls (6.9 months). These results support the hypothesis that a history of infertility predisposes women to an increased risk of tubal pregnancy. The authors also found that, among infertile women, about twice as many cases (14.3%) as controls (6.8%) were current fertility drug users (RR = 3.1; 95% CI = 1.1-9.1), which suggests that the use of fertility drug(s) may further increase the risk of tubal pregnancy.

Borderline ovarian tumors possess many of the same morphological features as their malignant counterparts, but they do not destructively invade the ovarian stroma, and the women in whom they develop generally have a favorable prognosis. Female residents of three urban counties of western Washington diagnosed with serous and mucinous borderline ovarian tumors between 1980 and 1985 (n = 116) were interviewed regarding past reproductive events. A random sample of women from the same counties (n = 158) was identified through random digit dialing and were interviewed. The risk of these ovarian tumors among women who had given birth to 1 or 2 children and to 3 or more children was, respectively, 0.7 and 0.4 that of nulliparous women. There was no consistent influence of increasing age at first live birth. Adjusting for parity, a history of lactation was associated with a 50% reduction in risk. Among nulliparous women, a further increase in risk was present in those who reported a history of infertility. Use of oral contraceptives was associated with a 60% reduction in risk. However, the size of the association was not dependent on duration, age at first use, or years since last usage. In conclusion, borderline tumors appear to have similar epidemiological patterns with regard to reproductive events as their more malignant counterparts.

To investigate the possible association between residential formaldehyde exposures and risk of cancer of the oro- and hypopharynx (OHPC, N = 205), nasopharynx (NPC, N = 27) and sinus and nasal cavity (SNC, N = 53), a population-based case-control investigation was carried out in 13 counties of western Washington. Controls (N = 552) were selected by random digit dialing. Subjects' residential histories, including type of dwelling, were determined from a structured telephone interview which also collected smoking, alcohol and demographic information. Multiple logistic regression was used to estimate exposure odds ratios (OR) while adjusting for known risk factors. A strong association was found between a history of having lived in a mobile home and NPC, but not OHPC or SNC. The NPC risk increased with the number of years lived in a mobile home: for those with 1 to 9 years the OR = 2.1 (95% confidence interval = 0.7-6.6), and for those with 10 or more years, the OR = 5.5 (95% CI = 1.6-19.4). No associations were found between any of the cancers and a history of exposure to new constructions containing particle board and plywood, or to urea-formaldehyde foam insulation. The association found with living in a mobile home must be interpreted with caution since it is based on a small number of cases, and may be due to factors other than formaldehyde. This report emphasizes the need for additional studies focusing on potential associations between indoor air pollutants and respiratory cancers.

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population-based, case-control study of ano-rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin-fixed, paraffin-embedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin-labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV-positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, 1 contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma-in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.

Data from a population-based case-control study conducted in Washington State and Utah were used to assess whether obesity is associated with an altered risk of epithelial ovarian cancer. Quetelet index, defined as weight (kg) at age 30 years divided by height (m) squared, was calculated for each woman, and the values for all subjects were divided into five categories of approximately equal size. Compared with women in the lowest category, women in the highest category had an odds ratio of 1.7 (95 per cent CI 1.1-2.7). Risks for women in the three intermediate Quetelet index categories also exceeded the risk for women in the lowest group, but to a much smaller degree. Among women with serous tumors, those in the highest Quetelet index category were at a greater than twofold excess risk (OR = 2.2, 95 per cent CI 1.1-4.2), but the risk was not increased in the intermediate categories. For endometrioid tumors, risk increased consistently with increasing Quetelet index, and the odds ratio in the highest category was 4.7 (95 per cent CI 1.0-22.7). For both serous and endometrioid tumors, the excess risk was largely confined to premenopausal women. The results of this analysis suggest that for at least some types of ovarian tumor, obesity may warrant further attention as a possible etiologic factor.

This case-control study was designed to investigate the relation between reproductive history and occurrence of hip and forearm fractures in postmenopausal women. Three hundred and fifty-five King County, Washington women who sustained a fracture between 1976 and 1980 and 562 control women were interviewed regarding their reproductive history and other factors. After controlling for the confounding effects of age, obesity, and use of noncontraceptive estrogens, the authors found that women who gave birth four or more times had a risk of fracture similar to women who had not given birth (odds ratio = 1.2, 95% confidence interval = 0.7-2.2), and women who breastfed for more than two years had a risk of fracture similar to women who had never breastfed (odds ratio = 0.8, 95% confidence interval = 0.4-1.5).

Adult white male residents of 13 counties of western Washington State in whom germ cell testicular cancer was diagnosed between 1977 and 1983 (n = 333) were interviewed by telephone regarding their history of cryptorchism and its treatment. The same interview was given to a sample of 675 men selected from the population of these counties by dialing telephone numbers at random. Men who reported a history of cryptorchism were 5.9 times (95 per cent confidence interval 3.4-10.2) more likely than men without such a history to develop testicular cancer. Compared with noncryptorchid men, those with unilateral cryptorchism were at greater risk of developing a tumor on the side of nondescent (relative risk = 8.0) than on the opposite side (relative risk = 1.6). The size of the increased risk tended to be smaller among cryptorchid men who had undergone orchiopexy by age 10 than for other cryptorchid men, but the influence of orchiopexy in early childhood could not be evaluated in this population. These observations offer support for the hypothesis that one or more local factors (e.g., temperature elevation) account for the major part of the increased risk of germ cell testicular tumors in cryptorchid men.

Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval = 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.

Three hundred seventy-six infertile women in whom there was evidence of ovulatory dysfunction were compared to fertile controls to determine if being excessively under or overweight at the time of planned conception was associated with an increased risk of infertility. In nulligravid women (n = 204), body weight for height 85% or less than "ideal" was associated with a 4.7-fold increase in risk (95% confidence interval = 1.5 to 14.7) of infertility associated with ovulatory dysfunction. Nulligravid women who were 120% or more over their ideal weight were also at increased risk for ovulatory infertility (relative risk = 2.1, 95% confidence interval = 1.0 to 4.3). Neither association was seen among women who had been previously pregnant. The presence of abnormalities of endocrinologic reproductive function in underweight and overweight women argues that the associations we have noted in nulligravid women represent cause-and-effect relationships. If so, we estimate that 6% of primary infertility in which ovulatory dysfunction is present results from being excessively underweight, and another 6% from being excessively overweight.

Female resident of King and Pierce Counties (Washington) in whom carcinoma of the colon or rectum was diagnosed during a 15-month period in 1976-77 were interviewed regarding their menstrual and reproductive histories. A random sample of women from the same population was interviewed for comparison. On the average, women with colon cancer had given birth to fewer children than had controls; compared to the incidence of colon cancer in nulliparous women, the incidence in women with 1 or 2 children was reduced by 30%, whereas the incidence in women with 3 or more children was reduced by 50% (P=0.004). No association was present between parity and rectal cancer. Neither contraceptive nor noncontraceptive estrogen use was related to the incidence of colon cancer. Use of oral contraceptives was more common among women with rectal cancer than among controls, but this result could well have arisen by chance (P=0.09). The data were not adequate to determine whether it was the inability to conceive and deliver a child that was related to colon cancer or the failure to undergo the physiologic changes that accompany pregnancy. Nonetheless, the association of low parity with the incidence of colon cancer has now observed several times, in each instance to a moderately strong degree. This observation suggests that events of reproductive life have a bearing on a woman's subsequent risk of developing colon cancer.

As part of a case-control study of tubal ectopic pregnancy (TEP), we sought to evaluate the possible etiologic role of use of an intrauterine device (IUD) prior to conception. We interviewed 155 women who had a tubal ectopic pregnancy treated at one of five Seattle, Washington hospitals between 1975-79 regarding their reproductive, contraceptive, and medical histories; 456 women who delivered a baby in King County during the same period were identified from vital records and interviewed as controls. An elevated risk of TEP was detected among former users of the Dalkon Shield (adjusted OR = 2.5; 95% CI = 1.3-4.7). Women who had used other IUDs did not have an excess risk of TEP.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

As part of a population-based case-control study carried out in four areas of the United States, 427 cases of chronic lymphocytic leukemia diagnosed between July 1, 1977, and December 31, 1981, and 1,683 controls were interviewed regarding their history of chemical exposure. Respondents were asked if they had ever been "highly exposed" at home, at work, or elsewhere to one or more of a list of chemicals or to any other such substances not on the list. These chemicals were categorized into 20 exposure groups based on chemical composition. Odds ratios were calculated adjusting for age, sex, race, education level, and geographic location by means of unconditional logistic regression. Increased risks were associated with reported past exposure to acid-containing chemicals, "other caustic substances," aliphatic hydrocarbons, and chlorinated hydrocarbons. Because of the large number of exposures investigated in this study, and because of the relatively imprecise means the authors had to assess exposure, further research is needed to verify these findings.

Adult male residents of 13 counties of western Washington state in whom testicular cancer had been diagnosed during 1977-1983 (n = 333) were interviewed over the telephone regarding their history of genital tract conditions, including vasectomy. For comparison, the same interview was given to a sample of 729 men selected from the population of these counties by dialing telephone numbers at random. A higher proportion of cases than controls reported having had a vasectomy (relative risk = 1.5, 95 per cent confidence interval = 1.0-2.2). However, the association was restricted entirely to Catholic men. Whereas a history of vasectomy was reported with approximately equal frequency by Catholic and non-Catholic cases, only 6.3 per cent of Catholic controls reported such a history in contrast to 19.7 per cent of other controls. While the authors cannot rule out the possibility that there is a true difference of the effect of vasectomy on the incidence of testicular cancer as a function of religion, it seems more plausible that selective underreporting by Catholic controls has produced a spurious relation.

We interviewed 49 women who had a history of condyloma acuminatum and 196 age-matched controls. For women who had ever smoked, the risk of developing condyloma was 3.7 times that of women who had never smoked (95% confidence interval, 1.8-7.6). The relative risk associated with long-term use (five or more years) of oral contraceptives was 9.8 (95% confidence interval, 1.5-65.6). Condyloma acuminatum is caused by infection with human papilloma virus (HPV), usually types 6 or 11. Infection with HPV, most commonly of other types, is associated with an increased risk of cervical neoplasia. If smoking and oral contraceptives increase the risk of infection with these other types of HPV as they do with types 6 and 11, this factor could be the means by which smoking and long-term use of oral contraceptives increase the incidence of cervical neoplasia.

As part of an epidemiologic study of cancer of the large bowel in women, female residents of King and Pierce counties (Washington) who were diagnosed during 1976--77 were interviewed regarding previous gallbladder surgery. Their responses were compared with those of a random sample of women from the same population. A history of cholecystectomy was somewhat more frequent among patients with colon cancer than among controls--we estimate the colon cancer risk in women without a gallbladder to be 1.4 times that of other women--but the 05% confidence limits of the relative risk included 1.0 (0.8--2.5). There was no association between cholecystectomy and rectal cancer and, among the subsites of colon cancer, the magnitude of the excess risk failed to show any consistent right--left gradient. Nonepidemiologic data suggest that cholecystectomy could increase the risk of colon cancer. However, if such an association truly exists it is not a strong one, and studies larger than those conducted to date are needed to detect this association reliably.

Response levels obtained from two methods of patient contact to obtain subject consent for participation in epidemiologic studies were compared. When a signed, return card was required prior to further contact, 70 to 83 per cent of patients consented to participate, compared with consistently higher levels (89 to 93 per cent) obtained with telephone contact. These data suggest that the likelihood of obtaining the high response level required in epidemiologic studies is increased by methods that do not rely on a return card.

The authors performed a population-based case-control study of the association between weather and occurrence of eclampsia in Washington State. Women who were recorded as having eclampsia on Washington birth certificates from 1980 to 1983 were compared to a random sample of all women who gave birth during those years. For each woman studied, National Oceanic and Atmospheric Administration weather data were used to determine the temperature, relative humidity, precipitation, and wind speed on the date of birth at the station nearest the hospital of birth. Categorical analysis revealed that eclampsia was not associated with low temperature, high relative humidity, precipitation, or high wind speed. These results were unchanged after adjustment for race, parity, maternal age, and late initiation of prenatal care. These results do not support an association between eclampsia and weather on the date of delivery in this population.

186 infertile women underwent standard infertility investigations (including hysterosalpingography and, in 87 women, laparoscopy) and tests for the presence of antibody to Chlamydia trachomatis. 73% of the women with distal occlusion of the fallopian tubes and 21% with peritubal adhesions alone had antibodies to C. trachomatis, but none of those with normal tubes did (p less than 0.001 and less than 0.005, respectively). No other infertility factors were associated with an increased frequency of antibodies to C. trachomatis. Since the presence or absence of antibodies to C. trachomatis was as discriminatory in the detection of tubal disease in infertile women as was the hysterosalpingogram, the serological test for C. trachomatis should become part of a routine infertility investigation.

To evaluate whether potent or prolonged stimulation of the immune system increases the risk of multiple myeloma, the authors compared 698 myeloma cases which occurred between July 1, 1977 and June 30, 1981 in four geographic areas of the United States with 1,683 demographically similar controls from the same areas. Cases and controls were interviewed about past exposures which may have involved antigenic challenge. Although few positive associations emerged, those most consistent with the immune stimulation hypothesis were modest associations between myeloma and a history of rheumatic fever (relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.09-2.77) and between myeloma and urinary tract infection (RR = 1.30, 95% CI = 1.00-1.69, when self-respondent cases were compared with controls). Little association was found between the risk of myeloma and the number of past viral illnesses, number of bacterial illnesses, or number of allergy desensitization injections. Myeloma risk was found to be inversely related to the number of diseases against which a subject reported having been immunized, perhaps because of differences in socioeconomic status between cases and controls. These findings provide little support for the immune system stimulation hypothesis of myeloma etiology, but because of the limitations of interview techniques for assessing antigen exposure, further studies using laboratory methods may be warranted.