Rivka Yanetz

Cancer Risk After Exposure to Treatments for Ovulation Induction

Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Coxs proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline-significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.

Preeclampsia and subsequent risk of cancer: update from the Jerusalem Perinatal Study

OBJECTIVE The purpose of this study was to examine the association between preeclampsia and cancer incidence. STUDY DESIGN The Jerusalem Perinatal Study is a population-based cohort of all births to 41,206 residents of Western Jerusalem from 1964-76. Cancer incidence to 2004 was assessed by linkage of the cohort with the Israel Cancer Registry. Coxs proportional hazards models were constructed to estimate the hazard ratio for cancer among women who had had preeclampsia. RESULTS Preeclampsia was associated with a 1.23-fold increased risk of cancer at all sites, a 37% increased risk of breast cancer, and more than a doubling of ovarian cancer risk. Analysis by morphologic condition yielded significantly increased risks for malignancies that were classed as cystic mucinous and serous (relative risk, 1.96; 95% CI, 1.00-3.83) and for ductal, lobular, and medullary carcinomas (relative risk, 1.40; 95% CI, 1.07-1.83). No differential association was observed by sex of offspring. CONCLUSION Our study suggests that the previously described protective effect of preeclampsia on cancer is not universal.

Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study

BackgroundDiabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28–40 years for whom information on diabetes had been collected at the time they gave birth, in 1964–1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up.MethodsWe used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring.ResultsWe observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14–35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8–18.0).ConclusionWe conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.

Late stillbirths and long-term mortality of mothers.

OBJECTIVE: To assess whether women who experienced stillbirths have an excess risk of long-term mortality. METHODS: We conducted a cohort study in the setting of the Jerusalem Perinatal Study, a population-based database of all births to West Jerusalem residents. Through data linkage with the Israeli Population Registry, we followed mothers who gave birth at least twice between 1964 and 1976 and compared the survival of women who had at least one stillbirth (n=595) with that of women who had only live births (n=24,523), using Cox proportional hazards models. RESULTS: During the study period, 78 (13.1%) mothers with stillbirths died, compared with 1,518 (6.2%) women without stillbirth (crude hazard ratio 2.08, 95% confidence interval [CI] 1.65–2.61). The mortality risk remained significantly increased after adjustments for sociodemographic variables, maternal diseases at pregnancy, placental abruption, and preeclampsia (hazard ratio 1.40, 95% CI 1.11–1.77). Stillbirth was associated with an increased risk of death from coronary heart disease (adjusted hazard ratio 2.00, 95% CI 1.02–3.93), all circulatory (adjusted hazard ratio 1.70, 95% CI 1.02–2.84) and renal (adjusted hazard ratio 4.70, 95% CI 1.47–15.0) causes. Stratifying by country of origin, an increased risk was evident particularly among women of North African origin (all-cause mortality, adjusted hazard ratio 2.47, 95% CI 1.69–3.63). CONCLUSION: Stillbirth may be a risk marker for premature mortality among parous women. LEVEL OF EVIDENCE: II

Ethnic ancestry and increased paternal age are risk factors for breast cancer before the age of 40 years.

To study the risk factors associated with breast cancer in women younger than 40 years, a cohort study (The Jerusalem Perinatal Study) of 42 822 female offspring born in hospitals in West Jerusalem during 1964–1976 was carried out. Hazard ratios of potential parental and perinatal risk factors for early breast cancer were measured. The overall incidence of breast cancer was 5.2/100 000 person–years. The highest incidence was found among Jewish women of West Asian ancestry (8.6/100 000 person–years), specifically those whose maternal grandfathers were born in Iraq, Iran or Afghanistan (9.5/100 000 person–years). Using Cox models we found independent risk factors for early breast cancer to be paternal age (relative risk/year=1.06, 95% confidence interval=1.02–1.10, P=0.005), and ancestry from Iraq/Iran/Afghanistan (relative risk=3.1, 95% confidence interval=1.50–6.52, P=0.002). The study confirms a previously observed effect of advanced paternal age on the occurrence of early breast cancer and identifies a novel population group at increased risk for the disease. The excess risk of early breast cancer associated with ancestry from Iraq, Iran and Afghanistan suggests involvement of genetic determinants, environmental exposures and/or lifestyle factors and mandates further investigation.