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S Harlap

Publications and source records attributed to S Harlap.

At least 19 recordsLinked to original sources
PubMed2006

Paternal age and spontaneous abortion.

OBJECTIVE: To evaluate the influence of paternal age upon spontaneous abortion. METHODS: This case-control study of 13,865 women draws on data from women's antenatal or postpartum interviews in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in 1964-1976. Case women (n=1,506) reported spontaneous abortion in the pregnancy preceding the interview; they were compared with women reporting live births in their previous pregnancy (n=12,359). Logistic regression was used to adjust for maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions before the index pregnancy, parity at interview, and interval between the index pregnancy and the interview. RESULTS: The adjusted odds ratio for spontaneous abortion was 0.59 (95% confidence interval 0.45-0.76, P< .0001) for pregnancies conceived from fathers aged younger than 25 years compared with those from fathers aged 25-29 years. For fathers age 40 years or older the odds ratio for spontaneous abortion was 1.6 (95% confidence interval 1.2-2.0, P=.0003) when compared with the same reference group. CONCLUSION: Increasing paternal age is significantly associated with spontaneous abortion, independent of maternal age and multiple other factors.

Abortion, Spontaneous↗
PubMed2005

Risk factors for pre-eclampsia in nulliparous and parous women: the Jerusalem perinatal study.

Pre-eclampsia has been described as a 'disease of first pregnancies' and many believe that its occurrence in a later pregnancy signals a fundamentally different entity. We sought to compare risk factors in first and subsequent pregnancies. We studied 1319 cases of pre-eclampsia recorded in a historical cohort of 82,436 deliveries in Jerusalem in 1964-76. Logistic regression was used to control for covariates. The adjusted odds ratio (OR) for pre-eclampsia in first births was 2.58 (95% confidence interval[CI] 2.23, 2.97), compared with all later birth order groups, between which there were no detectable differences in risk. Other risk factors included increasing maternal age, diabetes (OR 5.64, 95% CI 4.33, 7.35), multiple gestations (OR 3.38, 95% CI 2.54, 4.49), fetal haemolytic disease (OR 2.24, 95% CI 1.43, 3.50) and lower maternal education. The risk of pre-eclampsia was not associated with the mother's employment outside the home and did not differ between immigrants vs. Israeli-born mothers or between groups of women whose fathers had been born in Western Asia, North Africa or Europe. Effects of each risk factor were similar within first and subsequent births. These results lend no support to the hypothesis that there is a fundamental difference between pre-eclampsia in a first pregnancy compared with that occurring in a later pregnancy; conclusions may be moderated, however, by the knowledge that the incidence of pre-eclampsia was low in this historical cohort.

Adolescent↗
PubMed2004

Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer.

OBJECTIVE: One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. METHODS: In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T-->C (val-->ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G-->A substitution at the -463 position in the promoter region of MPO; and (3) the C-->T (pro-->ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. RESULTS: For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). CONCLUSIONS: While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.

Adult↗
PubMed2003

Birthweight and relationship with infant, child and adult mortality in the Jerusalem perinatal study.

There is growing evidence that several chronic adult diseases, such as coronary heart disease and stroke, can result from events occurring in fetal life. The aim of this study was to examine the relation between birthweight and all-cause mortality in young adults. We studied total mortality in a population-based cohort of 80 936 offspring born in Jerusalem in 1964-76. During an average follow-up of 28.8 years 2 324 984 person-years were contributed and 2092 deaths occurred. Overall, in both genders, the univariable and the multivariable Cox-proportional hazard models indicated a strong negative relationship between birthweight and total mortality, mostly because of infant deaths. At ages 1-14 birthweight seemed unrelated to all-cause mortality. In males aged 15+, birthweight was again a significant predictor of death (Hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.78, 0.99], for 1 standard deviation (SD) increase in birthweight). The analysis by categories suggested a general decreasing of the risk of mortality with increasing birthweight (HRs = 1.0, 1.02, 0.85, 0.77, 0.57 for those belonging to birthweight groups of < 2500 g, 2500-2999 g, 3000-3499 g, 3500-3999 g and > or = 4000 g, respectively). In females aged 15+ there was a J-shaped relation between birthweight and mortality but these associations were not statistically significant. These findings add to a growing body of evidence that events during intrauterine life have remote consequences for adult health and underline the need to consider gender differences.

Adult↗
PubMed2001

Advancing paternal age and the risk of schizophrenia.

BACKGROUND: A major source of new mutations in humans is the male germ line, with mutation rates monotonically increasing as father's age at conception advances, possibly because of accumulating replication errors in spermatogonial cell lines. METHOD: We investigated whether the risk of schizophrenia was associated with advancing paternal age in a population-based birth cohort of 87 907 individuals born in Jerusalem from 1964 to 1976 by linking their records to the Israel Psychiatric Registry. RESULTS: Of 1337 offspring admitted to psychiatric units before 1998, 658 were diagnosed as having schizophrenia and related nonaffective psychoses. After controlling for maternal age and other confounding factors (sex, ethnicity, education [to reflect socioeconomic status], and duration of marriage) in proportional hazards regression, we found that paternal age was a strong and significant predictor of the schizophrenia diagnoses, but not of other psychiatric disorders. Compared with offspring of fathers younger than 25 years, the relative risk of schizophrenia increased monotonically in each 5-year age group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95% confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 and 50 years or more, respectively. Categories of mother's age showed no significant effects, after adjusting for paternal age. CONCLUSIONS: These findings support the hypothesis that schizophrenia may be associated, in part, with de novo mutations arising in paternal germ cells. If confirmed, they would entail a need for novel approaches to the identification of genes involved in schizophrenia.

Adult↗
PubMed2001

Epithelial ovarian carcinoma and European birthplace of grandparents.

OBJECTIVE: The aim of this study was to determine whether the risk of ovarian carcinoma was related to latitude or to genetically based patterns of European geographic origin. PATIENTS AND METHODS: We studied the countries of origin of European-born grandparents of 168 newly diagnosed patients in two hospitals in New York City, compared with 159 controls from similar neighborhoods. We measured the risk of this cancer associated with having one or more white, non-Jewish grandparents born in North Europe versus none or in South Europe versus none. We also classified geographic origins in other ways to reflect the two main trends in genetic variations between Europeans mapped by Cavalli-Sforza et al. (The History and Geography of Human Genes, Princeton University Press, Princeton, 1994). Unconditional logistic regression was used to control for age, parity, years of use of oral contraception, age at menarche, education, Catholic religion, and area of residence and for numbers of Jewish grandparents, siblings, and first-degree relatives with breast or ovarian cancer. RESULTS: Approximately half of the subjects had least one white, non-Jewish grandparent born in Europe. There was no significant effect of ancestral latitude: among women born in the United States the odds ratio (OR) and 95% confidence limits associated with North European ancestry were 0.87 (0.47--1.63) compared with a reference group of women with no such ancestry. The corresponding OR for South Europe was 0.73 (0.39--1.74). Using the genetically based classifications of countries of origin, however, we found significant differences between cases and controls; ancestries from North West Europe and those from countries concentrically near Spain showed lower risks of ovarian carcinoma. CONCLUSIONS: The results support the hypothesis that the previously observed effects of latitude must act through environmental effects or through gene-environment interactions. Other variations in risk related to geographic origins are consistent with known patterns of genetic differences, but require confirmation in larger, population-based studies.

Adult↗
PubMed2001

Symptoms of ovarian cancer.

OBJECTIVE: To examine the symptoms of ovarian cancer in patients compared with symptoms experienced by healthy women using a case-control design. METHODS: Cases (n = 168) were women with ovarian cancer diagnosed at two hospitals in New York between 1994 and 1997 who were interviewed shortly after diagnosis. They were compared with healthy women (n = 251 controls) from the community. Women were asked about the prevalence, duration, and constancy of eight symptoms and about use of three types of medications in the 6 to 12 months before diagnosis (cases) or interview (controls). RESULTS: Nearly all the cases (93%) reported at least one symptom, compared with 42% of controls. The most common symptoms among cases were: unusual bloating, fullness, and pressure in the abdomen (71%); unusual abdominal pain or lower back pain (52%); and lack of energy (43%). The proportions of controls reporting these symptoms were 9, 15, and 16%, respectively, resulting in odds ratios and 95% confidence intervals of 25.3 (15.6, 40.9), 6.2 (4.0, 9.6), and 3.9 (2.5, 6.1), respectively, for these symptoms. Bloating, fullness, and pressure was of more recent onset among cases than controls (4.9 months compared with 7.6 months, P =.01). There were only minor differences in reported symptoms between cases with early and later stage disease. CONCLUSION: Unusual bloating, fullness, and pressure, abdominal or back pain, and lack of energy are prominent symptoms in women with ovarian cancer and distinguish them from controls. Information on symptoms may make women and physicians more aware of changes associated with ovarian cancer.

Adult↗
PubMed2001

Term infants with fetal growth restriction are not at increased risk for low intelligence scores at age 17 years.

OBJECTIVE: To assess the long-term cognitive outcome of small for gestational age (SGA) compared with appropriate for gestational age (AGA) infants. DESIGN: Data from the Jerusalem Perinatal Study was matched with information from the army draft medical board. SGA and severe SGA were defined as birth weight below the 10th and 3rd percentiles for gestational age, respectively. A multiple linear regression analysis was performed to control for clinical, perinatal, and socio-demographic confounding variables. SUBJECTS: A cohort of 13,454 consecutive singleton term infants born between 1974 and 1976. MAIN OUTCOME MEASURE: IQ at age 17 years. RESULTS: SGA infants had lower adjusted mean +/- SE IQ scores compared with their AGA peers: 102.2 +/- 0.9 versus 105.1 +/- 0.7 (P <.0001) for males and 102.5 +/- 0.9 versus 103.9 +/- 0.7 (P <.015) for females. SGA was not associated with lower academic achievements compared with AGA. CONCLUSION: After controlling for multiple confounders, being born SGA at term is associated with slightly lower intelligence test scores at age 17 years. However, the clinical significance of the small difference is not evident in academic achievements.

Adolescent↗
PubMed2001

Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.

Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer. None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day. In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption of antioxidants from diet was unrelated to risk. In analyses combining antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (> 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances. These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.

Adult↗
PubMed2001

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Adult↗
PubMed2000

Selection of control groups by using a commercial database and random digit dialing.

Identifying a control group when cases come from a specialized hospital is a challenge for epidemiologists. The authors compared controls recruited by using a commercial database with those recruited by random digit dialing in the context of a hospital-based case-control study of ovarian cancer. This part of the study was conducted in 1997-1998 among women aged 18 years or older who resided in the New York metropolitan area. A mailing list owner grouped cases into "lifestyle" clusters based on US zip+4 postal code microneighborhoods and generated a random sample of potential controls with the same distribution across the clusters. Controls recruited from the commercial database (n = 82) and from random digit dialing (n = 90) were similar in age and race. Women from the commercial database had somewhat more education and higher incomes and were more similar to the cases on these measures. The control groups resembled each other closely in terms of oral contraceptive use, nulliparity, and religion and differed from the cases on these measures. Response rates were similar for the two groups. Only 28% of the cases were included on the mailing list, indicating that it did not reflect the source population of the cases. Use of a commercial database provided a control group whose socioeconomic factors were similar to those of cases at a lower cost than when random digit dialing was used but did not result in a higher response rate.

Adult↗
PubMed1999

Helicobacter pylori infection on the risk of stomach cancer and chronic atrophic gastritis.

Helicobacter pylori infection is associated with gastric adenocarcinoma. However, the mechanisms of this interaction are still unclear. This study was conducted to explore the effects of H. pylori infection on early and late stage gastric carcinogenesis. This study included 134 patients with adenocarcinoma of the stomach (ACS), 67 patients with chronic atrophic gastritis (CAG), and 65 normal controls recruited at Memorial Sloan-Kettering Cancer Center (MSKCC) from November 1, 1992 to November 1, 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. H. pylori infection was diagnosed by pathological evaluation. Risk factors were analyzed using logistic regression. The odds ratio (OR) associated with H. pylori infection was 10.4 [95% confidence interval (CI): 2.6-41.6] for CAG and 11.2 (95% CI: 2.5-50.3) for gastric cancer in comparison with normal controls, with adjustment for pack-years of smoking, alcohol drinking, body mass index, total caloric intake, dietary fat and fiber intake, and Barrett's esophagus. But H. pylori infection was not associated with risk of stomach cancer when patients with stomach cancer were compared with patients with CAG (OR = 0.6, 95% CI: 0.3-1.3) after controlling for potential confounding variables. This association was persistent when only patients with both gastric cancer and chronic gastritis were considered as cases and patients with CAG were considered as controls (OR = 0.7, 95% CI: 0.3-2.0) in the multivariate analysis. Our results suggest that H. pylori infection may be involved in the early stage of development of CAG, but not in the development of stomach cancer from CAG, and indicate that strategies for prevention of stomach cancer should target the early stage to eliminate H. pylori infection in high-risk populations.

Adenocarcinoma↗
PubMed1998

Survival of premenopausal women with breast carcinoma: effects of menstrual timing of surgery.

BACKGROUND: It is controversial whether the timing of tumor excision relative to the menstrual cycle influences the survival of patients with breast carcinoma. METHODS: Premenopausal patients (n=614) who had surgery for invasive, nonmetastatic breast carcinoma during the period 1978-1988 participated in an epidemiologic survey, reporting their menstrual cycle length and the date of their last menses. We ascertained deaths from any cause before 1993. RESULTS: Using Cox modeling, we found a nonlinear variation in the relative risk (RR) of death according to the timing of surgery during the menstrual cycle. The curve was best described by a cosine transformation of a 28-day cycle. For patients who had breast carcinoma surgery on the estimated day of ovulation, the risk of death was 0.59 (95% confidence limits [CLI=0.39-0.89, P=0.013) compared with patients who had surgery at the approximate time of menses. We observed this for patients treated in 1978-1981 (RR=0.43, 95% CL=0.23-0.83, P=0.011) and 1982-1983 (0.25, 95% CL=0.10-0.63, P=0.003), but not in 1984-1988 (1.48, 95% CL=0.64-3.4). The difference observed for 1984-1988 was explained by a significant improvement in the mortality rate (P=0.0004) for women whose surgery took place during menses or near to the date predicted for the next menses. No such improvement for women who underwent breast carcinoma surgery around the time of ovulation was observed during the period 1984-1988. These changes were not explained by the performance of lumpectomy or the increasing interval between biopsy and tumor excision. CONCLUSIONS: The shape of the survival curve contradicted the idea that it could be explained by levels of circulating estradiol or progesterone. Because observations that surgery was affected by menstrual timing seem not to have persisted beyond the mid-1980s, this study should not be used to support recommendations that surgeons perform breast carcinoma surgery on any particular day of the menstrual cycle.

Adult↗
PubMed1998

Relation of time since last birth and parity to survival of young women with breast cancer.

We investigated whether survival was related to recent childbirth or parity in a cohort of 540 women diagnosed with breast cancer before the age of 45 years who were followed for up to 14 years. Women who had given birth within 2 years before their diagnosis of breast cancer were at increased risk of dying, compared with nulliparous women, with an adjusted relative risk of 3.1 (95% confidence interval = 1.8-5.4). There was a moderate association of parity with mortality, with an adjusted relative risk of 1.8 (95% confidence interval = 1.2-2.9) for women with three or more births, compared with nulliparous women.

Adult↗
PubMed1997

Adenocarcinomas of the esophagus and gastric cardia: the role of diet.

The incidence of adenocarcinomas of the esophagus and gastric cardia (ACEGC) has been increasing for the past 10-15 years in the United States. The reason for this increase is unknown. This hospital-based case-control study was conducted to assess the effects of dietary and nutritional factors on the risk of ACECG. A total of 95 incident cases with pathological diagnosis and 132 cancer-free controls were included in the study. Patients were recruited at Memorial Sloan-Kettering Cancer Center from 1 November 1992 to 1 November 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. Increased risk of ACEGC was significantly related to higher intake of dietary calories and fat after controlling for several potential confounding factors. Decreased risk of ACEGC was significantly associated with high ingestion of dietary fiber, lutein, niacin, vitamin B6, iron, and zinc. Higher intakes of vitamin A, beta-carotene, vitamin E, folate, phosphorus, and potassium were associated with a decreased risk of the disease, but these were not statistically significant. The study suggests that ACEGC can be preventable through dietary interventions.

Adenocarcinoma↗
PubMed1997

A case-case analysis of factors related to overexpression of p53 in endometrial cancer following breast cancer.

We studied 54 patients diagnosed with endometrial cancer between 1981 and 1994 following a diagnosis of breast cancer. We used a case-case analysis, comparing tumors with and without overexpression of the p53 gene product to evaluate the association of putative p53 mutations with tamoxifen use and other risk factors for endometrial cancer. Twenty-four % of the tumors showed strong positive staining for the p53 gene product. Tumors in a more advanced stage (stage 2, 3, or 4, compared to stage 1) were more likely to overexpress p53 [odds ratio (OR) = 4.2; 95% confidence interval (CI), 1.1-16.2], as were tumors with serous or clear cell, compared to endometrioid, histology (OR = 5.8; 95% CI, 1.3-26.5). There was a small association between p53 overexpression and treatment with tamoxifen for breast cancer (OR = 2.6; 95% CI, 0.69-9.8). There was a strong relationship between overexpression of p53 and having a first-degree relative with breast cancer (OR = 12.3; 95% CI, 2.6-57.4) and between overexpression of p53 and having an additional cancer, i.e., at sites other than breast or endometrium (OR = 7.9; 95% CI, 1.6-40.1). In this group of women, genetic predisposition to cancer, as reflected in family history of breast cancer and personal history of an additional primary cancer, was strongly associated with overexpression of p53 in endometrial tumors. The results suggest that use of tamoxifen may be associated with an increase in tumors that overexpress p53, although the results could be due to chance.

Adult↗
PubMed1996

Adult height and risk of breast cancer among white women in a case-control study.

Data from a hospital-based case-control study were analyzed to evaluate the relation of adult height to the risk of breast cancer among white women. The authors compared 5,358 newly diagnosed breast cancer cases and 4,555 controls interviewed from 1976 to 1992 in hospitals located mainly in the United States. Overall, there was no association between stature and risk of breast cancer. In comparison with women whose heights were less than 62 inches (< 158 cm), the adjusted odds ratios were 1.1 (95% confidence interval (Cl) 0.9-1.2), 1.0 (95% Cl 0.9-1.2), 1.0 (95% Cl 0.9-1.1), and 1.0 (95% Cl 0.8-1.2) for women with heights of 62-63, 64-65, 66-67, and > or = 68 inches (equivalent to 158-160, 163-165, 168-170, and > or =173 cm), respectively. There was no consistent evidence of modification of the effect of height by other risk factors. The results suggest that adult stature in white women is not related to the risk of breast cancer.

Adult↗