The risk of liver cancer in relation to use of oral contraceptives was evaluated in a hospital-based case-control study conducted in five US cities from 1977 to 1985. Twelve new cases of liver cancer were identified in women aged 19-54 years; five controls selected from among patients hospitalized for acute conditions unrelated to oral contraceptive use were matched to each case on age (five-year categories), date of interview (three-year categories), and geographic location of the hospital. Among nine cases classified as having hepatocellular carcinoma, eight (89%) had used oral contraceptives; only 16 (36%) of 45 matched controls had used oral contraceptives. Among three other cases (two with cholangiocarcinomas and one with liver cancer of undetermined type), all had used oral contraceptives, compared with four of 15 matched controls. The results confirm the strong positive association between oral contraceptive use and hepatocellular carcinoma observed in earlier studies. Such an association is consistent with evidence that oral contraceptive use is associated with benign hepatic tumors in young women. However, the number of cases of liver cancer in the United States that are attributable to oral contraceptive use is probably small, because liver cancer is extremely rare in the United States.
The relation between the risk of breast cancer before 45 years of age and oral contraceptive use was examined in a case-control study conducted in New York, Philadelphia, Baltimore, and Boston from 1983 to 1986 of 407 patients with breast cancer and 424 controls. With allowance for confounding, for ever use, the multivariate relative risk estimate was 2.0 (95% confidence interval (CI), 1.4-2.9). For less than 10 years of use, the estimate approximated 2.0 in all categories of duration, including less than three months; for 10 or more years of use it was 4.1 (95% CI, 1.8-9.3). The association was apparent in virtually all subgroups examined, including younger and older women, and women at low and high underlying risk of breast cancer. Contrary to some previous reports, the association was not stronger for use before a first term pregnancy or at an early age. The results suggest that oral contraceptive users, particularly those with very long durations of use, may be at increased risk of breast cancer. However, information bias, particularly for short-term use, could not be ruled out. There may also have been selection bias if oral contraceptive users were under more intensive medical surveillance. It has not been possible to reconcile the findings of the various studies to date, including the authors' earlier results showing no association. The latter results were derived from data collected using methods almost identical to those used in the present study.
Because the role hormonal and reproductive factors play in the etiology of endometrial cancer is incompletely understood, the authors evaluated the risk of this cancer in relation to age at last delivery. The data were obtained in a hospital-based case-control study of 483 women with endometrial cancer (cases) and 693 women with other conditions (controls) conducted in a number of hospitals in the United States and Canada from 1978 to 1985. There was an inverse association between age at last delivery and endometrial cancer risk: Compared with women who last gave birth before age 25 years, the rate ratio was 0.9 (95% confidence interval (CI) 0.5-1.6) for last delivery at ages 25-29 years, 0.6 (95% CI 0.3-1.0) for last delivery at ages 30-34 years, 0.5 (95% CI 0.3-1.0) for last delivery at ages 35-39 years, and 0.4 (95% CI 0.1-0.9) for last delivery at age 40 years or older. The trend of decreasing rate ratio with increasing age at last delivery was statistically significant (p = 0.02). The association was apparent regardless of parity or menopausal status. There was no evidence for an association between age at first pregnancy and risk. These data suggest that women who bear children late in reproductive life may be at lower risk for endometrial cancer than those who complete their families early.
The relation of acute thrombocytopenic purpura (TP) to the use of drugs was investigated in a case-control study conducted in eastern Massachusetts, Rhode Island, and the Philadelphia region; 62 cases over the age of 16 years with acute onset and with a rapid recovery were compared with 2,625 hospital controls. After control for confounding by multiple logistic regression, use of the following drugs in the week before the onset of symptoms was significantly associated: trimethoprim/sulfamethoxazole (relative risk [RR] estimate, 124), quinidine/quinine (101), dipyridamole (14), sulfonylureas (4.8), and salicylates (2.6). The overall annual incidence of acute TP was estimated to be 18 cases per million population. The excess risks for the associated drugs were estimated to be 38 cases per million users of trimethoprim/sulfamethoxazole per week, 26 per million for quinidine/quinine, 3.9 per million for dipyridamole, 1.2 per million for sulfonylureas, and 0.4 per million for salicylates. Associations with sulfonamides, quinidine/quinine, sulfonylureas, and salicylates have been previously reported, but the present study has provided the first quantitative measures of the risk. The association with dipyridamole was unexpected. In general, despite large RRs, the incidence rates attributable to the drugs at issue (excess risks) were low, suggesting that TP is not an important consideration in the use of the various drugs.
To evaluate whether vasectomy is associated with a subsequent increase in the incidence of myocardial infarction 10 or more years after surgery and whether an effect is more pronounced in those already predisposed to a myocardial infarction, a hospital-based case-control study was carried out in men aged less than 55 years. The men were interviewed during 1980-1983 in 78 hospitals in Massachusetts, Rhode Island, Connecticut, and New York. Among 2,238 men with first episodes of myocardial infarction, 332 (15%) had undergone vasectomy, compared with 572 (16%) of 3,361 controls. Vasectomy greater than or equal to 10 years earlier was reported by 150 cases and 180 controls, to yield a multivariate relative risk estimate of 1.0 after allowance for potential confounding factors (95% confidence interval (Cl) = 0.8-1.3); for vasectomy greater than or equal to 15 years before, based on 34 cases and 33 controls, the estimate was 1.1 (95% Cl = 0.7-2.0). In men predisposed to myocardial infarction because of more advanced age, cigarette smoking, elevated cholesterol level, hypertension, angina pectoris, or other risk factors, vasectomy did not appear to increase the risk further, even after intervals of greater than or equal to 10 years. The results provide evidence against an increased risk of myocardial infarction greater than or equal to 10 years after vasectomy overall and in those known to be predisposed because of other risk factors.
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