Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter.

Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race-matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant.

Vasectomy, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men.

A population-based case-control study was conducted in men aged 60 or less to assess the risk of prostate cancer associated with vasectomy and other factors. Data were obtained from 216 case-control pairs by telephone interviews; this number represented 55% of all eligible cases. The matched pairs relative risk (RR) for vasectomy in ever married men was 1.4 with a 95% confidence interval (CI) of 0.9-2.3. There was a positive association between the number of years since vasectomy and prostate cancer risk (1-sided P = 0.01). Early age at first sexual intercourse was associated with increased prostate cancer risk (age less than 17 vs. 21+, RR = 2.3, 95% CI = 1.3, 4.0) but there were no consistent associations with number of sexual partners or frequency of sexual intercourse. Cigarette smoking was also associated with increased risk of prostate cancer (RR = 1.9, 95% CI = 1.2, 3.0) and there was a positive dose-response relationship with years of smoking (1-sided P = 0.001). We discuss the possible implication of the low response rate on each of these findings. To determine whether the association with vasectomy might have a hormonal basis, we compared levels of testosterone (T) and testosterone binding globulin-binding capacity (TeBG-bc) in 33 of the vasectomized control men with levels in 33 non-vasectomized controls of the same age, weight and height. T levels were higher in vasectomized than in non-vasectomized controls (1-sided P = 0.06). The ratio of T to TeBG-bc (an index of bioavailable T) was 13.5% higher in vasectomized men (1-sided P = 0.03).

Effects of reserpine on prolactin levels and incidence of breast cancer in postmenopausal women.

Epidemiological studies of reserpine use and breast cancer have generally found only small increases in breast cancer risk, even after long-term use. Prolactin levels in short-term reserpine users have been reported to be in the range of those of lactating women, levels which rodent experiments suggest should greatly increase breast cancer incidence. We measured prolactin levels in 15 women who had been taking reserpine-containing drugs for at least 5 years and compared them to levels in 15 women taking non-reserpine-containing antihypertensives and 15 women taking no antihypertensive medicines. Although reserpine users had significantly elevated levels of prolactin, their mean level was only approximately 50% greater than the mean level of the combined results from the two control groups. Based on a statistical model of breast cancer incidence, we calculate that such increases in prolactin in the postmenopausal period would be likely to cause only small increases in breast cancer risk, as have been observed in epidemiological studies.

Menopausal estrogen therapy and hip fractures.

The association between menopausal estrogen therapy and hip fracture was studied in a retirement community. Ninety-one hip fracture cases during a 5-year period in female residents under age 80 were compared to age-and race-matched community controls. Estrogen use was recorded from the medical records of the outpatient care facility and personal interviews. The estimated risk ratio for use of oral estrogens in excess of 60 months was 0.42. This protective effect was largely limited to oophorectomized women for whom the risk ratio for a comparable duration of use was 0.14; the risk significantly decreased with increased duration, but no such trend existed with increased dosage. Diabetes mellitus, low Quetelet's index, tallness, prolonged immobilization or physical inactivity, use of corticosteroids, early age at menopause, low levels of sunlight exposure, and heavy cigarette smoking were each independent risk factors for hip fracture but none confounded the observed association with estrogen use.

Elevated levels of prolactin in nulliparous women.

Follicular-phase (Day 11) plasma prolactin, and plasma and urinary oestrogen levels of 70 nulliparous nuns were compared with those of 80 of their sisters, of whom 62 were parous. The nuns and their nulliparous sisters did not differ significantly in their prolactin and oestrogen levels. No differences in plasma oestrogens or urinary oestriol ratio were found between the parous and the nulliparous women. However, the mean prolactin level of the nuns and their nulliparous sisters was 35% higher than that of the parous women in the sample taken approximately 1 3/4 h after rising (p less than 0.0005), and 24% higher (P less then 0.01) in the 2nd sample taken 2 h later. The elevation was independent of age, weight, and age at menarché. Age at first full-term pregnancy, at least up to the age of 30, and second or subsequent full-term pregnancies had no further effect on prolactin level. This study suggests that the effect of early first full-term pregnancy in lowering breast cancer risk may be mediated, at least in part, by permanently lowering the level of circulating prolactin.

A case-control study of menopausal estrogen therapy and breast cancer.

The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities. The 138 study cases of breast cancer occurring in residents younger than 75 years were compared with age- and race-matched community control subjects. The risk ratio for a total cumulative dose in excess of 1,500 mg was estimated to be 2.5 in women with intact ovaries. This increase was present using various independent sources of drug usage information but was inconsistent at low dose and undetectable in oophorectomized women. No important sources of confounding could be identified, and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease. In such women with intact ovaries, the risk ratio for a high cumulative dose rose to 5.7 relative to nonusers with normal breasts.

The hormonal basis of breast cancer.

Both animal experiments and certain well-established breast cancer risk factors suggest that risk to the disease is fundamentally determined by the hormones of the pituitary-gonadal axis. Although international comparisons of urinary estrogens have given support to this ypothesis, case-control studies and international comparisons of plasma estrogens and prolactin have not. Methodological problems and sampling biases probably account for the inconsistency of these investigations. Taking advantage of the known familial increased risk to breast cancer, we conducted comparative studies of teenage daughters of patients with breast cancer, including a group of girls whose mothers had bilateral breast cancer when they were less than 50 years old. The results of these studies revealed that these high-risk girls appear to have elevated levels of estrogens, prolactin, and progesterone.

Comparison of urinary and plasma hormone levels in daughters of breast cancer patients and controls.

Plasma and urinary levels of estrogens and progesterone were studied on days 11 and 22 of the menstrual cycle in 27 teenage daughters of breast cancer patients and 25 teenage daughters of controls. Plasma and urinary values correlated well, which implied that most previous findings based on urinary levels of these hormones were applicable to their plasma levels. The "estriol ratio" (urinary estriol:urinary estrone plus estradiol) hypothesis was not supported by this study, the ratio having been no lower in the daughters of breast cancer patients than in daughters of controls. The day-11 results showed elevated plasma prolactin-estrogen values in daughters of breast cancer patients; the day-22 results did not.

Estrogens and endometrial cancer in a retirement community.

All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer.

Exogenous estrogens and breast cancer in women with natural menopause.

Age, age at menopause, and calendar year at menopause were controlled as factors related to estrogen use. Data on 90 breast cancer patients and 83 conrols--all of whom had a natural menopause--showed no relationship between breast cancer and estrogen usage after the start of menopause symptoms.

PIP: 90 breast cancer patients aged 50-64 were compared with 83 controls matched for age, race, and socioeconomic class to determine the relationship between administration of exogenous estrogens and breast cancer when the factors of age, age at menopause, and calendar year were controlled. No harmful effect of estrogen administration was demonstrat ed, but a previous finding by the authors of a beneficial effect was neg ated. It is suggested, however, that there are still too many confounding factors in a study of this type for a harmful association to be revealed, and it is recommended that a case-control study be carried out in a large prepaid medical care system.

Elevated serum levels of estrogen and prolactin in daughters of patients with breast cancer.

Demographic risk factors in sisters and daughters of 150 patients with breast cancer were compared to those of controls. Plasma hormone levels in 36 teen-age daughters of patients and 31 controls were also studied to ascertain whether an "abnormal" hormone pattern underlies these risk factors. The patients' sisters had, on the average, menarche four months earlier and first full-term pregnancy 12 months later than the controls. The patients' daughters did not show these differences -- apparently owing to low fertility in the patients with early menarche. The patients' daughters had higher 22d-day estradiol-plus-estrone levels than controls (24.4 vs. 19.1 ng per 100 ml, P less than 0.05). Sixth-day prolactin was also elevated (19.0 vs. 14.2 ng per 100 ml, P less than 0.05). About half the patients' daughters could clearly be distinguished from the controls' daughters by means of the sixth-day information on both estrogens and prolactin. Hypersecretion of these hormones may be important factors in breast cancer.

Reserpine and breast cancer in a retirement community.

In an attempt to confirm three reports suggesting a causal link between rauwolfia antihypertensive drugs and female breast carcinoma, all cases of such cancer appearing among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Most residents use a single care facility, and patterns of hypertension diagnosis, rauwolfia and other drug use, and medical-care-system patronage were abstracted from medical records. The prevalence of recorded rauwolfia use among the controls were 20 per cent, and that of other drug use was correspondingly high. The risk ratio for rauwolfia use was estimated to be 1.2 (95 per cent confidence interval, 0.7 to 2.2). Risk ratios between 1.0 and 2.0 were also found for other drug use and for measures of care-system patronage. These results do not support the hypothesis that reserpine causes breast cancer.