Reproductive, genetic, and dietary risk factors for ovarian cancer.

A case-control study of 110 women with ovarian epithelial carcinoma and 220 individually age-matched controls was conducted in Hokkaido, Japan, to identify ovarian cancer risk factors. Both the cases and the matched controls were surveyed either from 1980 to 1981 or from 1985 to 1986. Ovarian cancer risk was increased in single women (p less than 0.01), and in women with a family history of breast, uterine, or ovarian cancer in a mother or sister (p less than 0.001). Conversely, risk was decreased in women who had experienced a livebirth (p less than 0.001), an induced abortion (p less than 0.05), or who had had permanent sterilization by tubal ligation (p less than 0.05). Each of the reproductive factors remained significant when adjusted for each other using logistic regression analysis. The odds ratio for ovarian cancer decreased significantly with increasing number of livebirths (p less than 0.001). Furthermore, a significant negative association between anovulatory periods and ovarian cancer risk was noted (p less than 0.01). No association was observed for any types of contraceptive methods other than tubal ligation, but the prevalence of oral contraceptive use was very low. A significant positive association with daily fish consumption (p less than 0.05) and a marginally significant negative association with daily milk consumption (p = 0.05) were also observed.

A case-control study of male breast cancer.

A case-control study was conducted in Los Angeles County, CA, of 75 male breast cancer cases aged 20-74 yr at diagnosis to investigate the role of a number of suspected risk factors. The study involved both interviews and laboratory measurements. Factors under study included fertility and marital history, obesity, alcohol and cigarette consumption, use of drugs known or suspected of causing gynecomastia, family history of breast cancer, history of radiation exposure to the upper body, sex chromatin analysis, serum levels of prolactin, testosterone, estrone, estradiol and sex-hormone-binding globulin, as well as urinary levels of estrone, estradiol, and estriol. Two patients versus no controls tested positive for sex chromatin and were excluded from further analyses. The only statistically significant risk factor identified was greater weight of the cases at age 30; a man who weighed 80 or more kg at age 30 had twice the risk of breast cancer of a man weighing less than 60 kg at that age. Serum estrone levels were positively, and sex-hormone-binding globulin levels were negatively, related to body weight, and we interpret the greater weight of the cases as suggesting that the underlying risk factor is an increased exposure to bioavailable estrogen. None of the differences observed between cases and controls for either the serum or urinary hormone levels was, however, statistically significant and there did not appear to be any large absolute excess of estrogens or deficit of testosterone in the cases. This apparent contradiction may be explained by the fact that there was little difference in weight between the cases and controls at the time of sampling.

Risk factors for uterine fibroids: reduced risk associated with oral contraceptives.

Risk factors for pathologically confirmed uterine leiomyomas (fibroids) were investigated using data from the Oxford Family Planning Association study, a long term follow up study of women using various methods of contraception. For each of 535 women who had had a fibroid an individual control was selected who matched the patient on age, date of entry into the cohort, and family planning clinic at recruitment and who was alive (and still being followed up) at the date the patient underwent surgery for fibroids. Case-control analysis showed that reproductive experiences were closely linked to development of fibroids. Risk of fibroids decreased consistently with increasing number of term pregnancies; women with five term pregnancies had only a quarter of the risk of women who had had none. Risk also decreased consistently with increasing duration of oral contraceptive use; the risk of fibroids was reduced by some 31% in women who had used oral contraceptives for 10 years. Risk was strongly related to weight: women who weighed under 55 kg had a particularly low risk, and overall the risk rose roughly 21% for each 10 kg increase. Cigarette smoking was associated with a decreased risk of fibroids; smokers of 20 cigarettes a day had a risk roughly two thirds that of non-smokers. These risk factors have all previously been identified as risk factors for endometrial cancer; this strongly suggests that the underlying risk factor is "unopposed" oestrogen.

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study.

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.

Familial breast cancer in a population-based series.

Breast cancer risks to sisters of breast cancer patients were examined in a population-based series of patients diagnosed in Los Angeles County between 1971 and 1975. Sisters of bilateral patients diagnosed at age 50 years or younger had substantially increased risk (relative risk (RR) = 5.5), and risk was even higher for sisters of bilateral patients diagnosed at age 40 years or younger (RR = 10.5). Half of the breast cancers in sisters of bilateral cases occurred in the family of a single bilateral patient whose disease was diagnosed at age 39 years. Sisters of unilateral patients diagnosed at age 50 years or younger did not have significantly increased risk, but sisters of unilateral patients diagnosed at age 40 years or younger appeared to have increased risk (RR = 2.4). Risk to sisters of bilateral patients was slightly higher if the patient's contralateral diagnoses were less than three years apart than if they were three years apart or greater (RR = 6.3 vs. 3.9), but this difference was not statistically significant.

Kaposi's sarcoma in Los Angeles, California.

The demographic characteristics of "classic" Kaposi's sarcoma (KS) and of "epidemic" KS in Los Angeles, CA, were compared with the use of data from the Cancer Surveillance Program, the population-based tumor registry in Los Angeles County. The data obtained document the magnitude of the excess risk of classic KS for Jewish men of European (especially Eastern and Southern European) origin. The data also show in a systematic way the magnitude of the increase in acquired immune deficiency syndrome-related KS in one large urban area of the United States. In addition, they demonstrate that the demographic risk factors of religion and birthplace for classic KS are unrelated to epidemic KS and that the clinical presentation in terms of stage and primary site of classic KS is distinct from that of the epidemic form of the disease.

The epidemiology of endometrial cancer in young women.

A case-control study was conducted in Los Angeles County, California, of 127 endometrial cancer cases aged 45 years or less at diagnosis, to investigate the role of fertility, obesity and exogenous oestrogens in the development of the disease in young women. Use of sequential oral contraceptive (SOCs) or oestrogen replacement therapy (ERT) for greater than or equal to 2 years was strongly associated with increased risk of endometrial cancer. After excluding these cases, since the SOC or ERT use was probably the cause of their disease, we were left with 110 case-control pairs for further study. Among these remaining case-control pairs increasing parity was strongly associated with decreased risk (relative risk of 0.12 for women of parity 3 compared to nulliparous women, P less than 0.001). Current weight was associated with increased risk (relative risk of 17.7 for women weighing greater than or equal to 190 lbs compared to women weighing less than 130 lbs, P less than 0.001). Combination oral contraceptive (COC) use was associated with a decreased risk, which decreased with duration of COC use (relative risk of approximately 0.28 at 5 years of use, P less than 0.001), but the estimate of the protective effect was reduced and became statistically non-significant when allowance was made for weight and parity. The protective effect of COC use was only clearly evident in women who had less than 3 live-births and weighed less than 170 lbs. These results provide further support for the "unopposed" oestrogen hypothesis of the aetiology of endometrial cancer.

PIP: A case-control study was conducted in Los Angeles County, California, of 127 endometrial cancer cases aged 45 years or less, in order to investigate the role of fertility, obesity, and exogenous estrogens in the development of the disease in young women. Use of sequential oral contraceptives (OCs) or estrogen replacement therapy (ERT) for or= 2 years was strongly associated with increased risk of endometrial cancer. After excluding these cases since the OCs or ERT use were probably responsible for their disease, we were left with 110 case control pairs for further study. Among these remaining case control pairs, increasing parity was strongly associated with decreased risk (relative risk of 0.12 for women of parity 3 compared to nulliparous women, P0.001). Current weight was associated with increased risk (relative risk of 17.7 for women weighing or= 190 pounds compared to weighing 130 pounds, P0.001). Combination OC use was associated with a decreased risk, which decreased with duration of combination OC use (relative risk of approximately 0.28 at 5 years of use, P0.001), but the estimate of the protective effect was reduced and became statistically nonsignificant when allowance was made for weight and parity. The protective effect of combination OC use was only clearly evident in women who had less than 3 live births and weighed less than 170 pounds. These results provide further support for the unopposed estrogen hypothesis of the etiology of endometrial cancer.

'Hormonal' risk factors, 'breast tissue age' and the age-incidence of breast cancer.

For most cancer sites there is a linear log-log relationship between incidence and age. This relationship does not hold for breast cancer, and certain 'key' breast cancer risk factors suggest that breast tissue does not 'age' in step with calendar time. A quantitative description of 'breast tissue age' is suggested which brings the age-incidence curve of breast cancer into line with the common log-log cancers and explains quantitatively the known key risk factors. The model also explains the 'anomalous' finding that although early first birth is protective, late first birth carries a higher risk than nulliparity. US breast cancer rates are some four to six times the rates in Japan--the model suggests that the key risk factors, when considered jointly with weight, can explain about 85% of the difference.

Oral contraceptives and ovarian cancer.

PIP: Cramer et al. reported the results of a case control study of ovarian cancer in women under age 60, indicating that oral contraceptive (OC) use was associated with a decreased risk of the disease. Yet, according to Cramer et al. the decreased risk was evident only in women over age 40 and that below this age OC use was actually associated with an increased risk of ovarian cancer. As other workers had not broken down the data in this manner, Cramer et al. were unable to compare this result with the results from other studies. This group of researchers has reanalyzed their data to allow such a comparison. In contrast to the results of Cramer et al. it was found that only in the young cases was their any possible negative association between OC use and ovarian cancer. The data for both women under and over 40 showed a steady decrease in ovarian cancer with increasing duration of OC use.^ieng

Endogenous hormones as a major factor in human cancer.

Hormone-related cancers account for almost 30% of all cancer cases in the United States. Data from animal experiments and from epidemiological and endocrinological studies in humans support the hypothesis that the individual hormones which control normal growth of target organs can also create the proper conditions for neoplastic transformation. The concept that hormones can cause, i.e., increase the incidence of, human cancer is most developed for the four hormone-related cancers which are numerically the most important, namely, breast, prostate, endometrium, and ovary. Even for these sites, large gaps remain in our knowledge of the responsible hormones and the conditions which create the optimal opportunity for carcinogenesis. Although scanty, the available epidemiological evidence also suggests a hormonal role in the pathogenesis of testis cancer, thyroid cancer, and osteosarcoma. We believe that the primary prevention of all these cancers will probably depend on modification of the factors which affect the secretion and metabolism of the responsible hormones rather than on control of exposure to classical exogenous initiators.

Epidemiological characteristics of adenocarcinoma of the lung in Los Angeles County.

The descriptive epidemiology of adenocarcinoma of the lung was compared with that of squamous cell carcinoma with the use of data for 1972-76 from the population-based cancer registry serving Los Angeles County. Several differences in the demographic characteristics between these two types of lung cancer were observed, including low male-to-female ratios and lack of social class gradients for adenocarcinoma. Cigarette smoking was responsible for 90% of squamous cell carcinoma in both men and women and for 79% of male and 46% of female adenocarcinoma. We also studied incidence rates of lung cancer after subtraction of the proportion of the incidence due to smoking by using data from a previously conducted case-control study in Los Angeles County. These residual rates for squamous cell carcinoma showed a fivefold excess in males compared with females, whereas those for adenocarcinoma were almost the same in men and women. These findings indicate that 1) smoking is etiologically less important for adenocarcinoma than for squamous cell carcinoma, and 2) other etiologic factors for adenocarcinoma affect women as much as men.

Oral contraceptive use and early abortion as risk factors for breast cancer in young women.

A case-control study was conducted in Los Angeles County, California, of 163 very young breast-cancer cases (all aged 32 or less at diagnosis) to investigate the role, if any, of oral contraceptives (OC) in the development of the disease. OC use before first full-term pregnancy (FFTP) was associated with an elevated risk, which increased with duration of OC use (relative risk approximately 2.2 at 6 years of use, P < 0.01). This increased risk could not be explained by other risk factors. OC use after FFTP was not associated with any change in risk. A first-trimester abortion before FFTP, whether spontaneous or induced, was associated with a 2.4-fold increase in breast-cancer risk (P < 0.005).

PIP: A case control study was conducted in Los Angeles County, California of 163 breast cancer cases (all aged 32 or less at diagnosis) to determine the role, if any, of oral contraceptives (OCs) in the development of the disease. The patients were white women with microscopically confirmed breast cancer 1st diagnosed between July 1972 and December 1978. The patients were identified by the University of Southern California Cancer Surveillance Program (CSP), the population based cancer registry for Los Angeles County. 2 individually matched controls were sought for each of the 163 study patients. The 1st control was a neighborhood control, and the 2nd a friend control. The relative risk for breast cancer was statistically significantly increased by a history of the disease in mother or sister, by a history of benign breast disease, by earlier menarche, and by longterm use of OCs. The relative risk was decreased by having had a full-term (28 weeks or longer) pregnancy, but the result was not statistically significant. There was no clear trend with the age at 1st full-term pregnancy. Relative risk for OC use was roughly doubled if only use before 1st full-term pregnancy was considered. Relative risk was 3.5 for 8 or more years' use before 1st full-term pregnancy, and the trend of increasing relative risk with increasing duration of use was statistically highly significant. A 1st trimester abortion before 1st full-term pregnancy, whether spontaneous or induced, was associated with a 2.4-fold increase in breast cancer risk.

Chemosensitivity of human neoplasms with in vitro clone formation. Experience at the University of Southern California - Los Angeles County Medical Center.

We analyze experience with 600 specimens for in vitro chemosensitivity assessment of human neoplasms utilizing a soft agar colony-forming technique. Good test reproducibility is demonstrated. Disaggregation with collagenase enhances yield and does not alter chemosensitivity profiles. Therapeutic exposure to chemotherapy prior to biopsy reduces in vitro sensitivity to the specific agents used in vitro. The cyclophosphamide derivatives 4-hydroperoxycyclo phosphamide (4-HC) and phosphoramide mustard are active in vitro, and produce comparable rank order sensitivities among tested tumors. There is marked reduction of in vitro 4-HC sensitivity in patients with prior therapeutic cyclophosphamide exposure, supporting the use of this derivative in test systems. Rank order of test results among specimens is compared at 0.1 microgram and 10 microgram drug/ml. Substantial differences in rank order at these two dose levels are demonstrated, indicating that the in vitro test dose selected is an important variable.