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P Hartge

Publications and source records attributed to P Hartge.

At least 37 records · Page 2Linked to original sources
PubMed1999

Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Studies of survival following breast and ovarian cancers in BRCA1 and/or BRCA2 mutation carriers have yielded conflicting results. We undertook an analysis of a community-based study of Ashkenazi Jews to investigate the effect of three founder mutations in BRCA1 and BRCA2 on survival among patients with breast or ovarian cancer. METHODS: We collected blood samples and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (single nucleotide insertion) mutations in BRCA1 and the 6174delT (single nucleotide deletion) mutation in BRCA2. To estimate survival differences in the affected relatives according to their BRCA1 and/or BRCA2 mutation carrier status, we devised and applied a novel extension of the kin-cohort method. RESULTS: Fifty mutation carriers reported that 58 of their first-degree relatives had been diagnosed with breast cancer and 10 with ovarian cancer; 907 noncarriers reported 979 first-degree relatives with breast cancer and 116 with ovarian cancer. Kaplan-Meier estimates of median survival after breast cancer were 16 years (95% confidence interval [CI] = 11-40) in the relatives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarriers, a difference that was not statistically significant (two-sided P = .87). There was also no difference in survival times among the 126 first-degree relatives with ovarian cancer. We found no survival difference between patients with breast or ovarian cancer who were inferred carriers of BRCA1 and/or BRCA2 mutations and noncarriers. CONCLUSIONS: Carriers of BRCA1 and BRCA2 mutations appeared to have neither better nor worse survival prognosis.

Adult↗
PubMed1999

The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews.

Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain.

Adult↗
PubMed1999

Histopathologic features of ovaries at increased risk for carcinoma. A case-control analysis.

In this study, the pathogenesis of ovarian carcinoma was investigated by performing a masked histopathologic comparison of benign ovaries removed from 61 women predicted to be at increased risk for developing carcinoma (cases) with ovaries removed from 121 women without known predisposing conditions (controls). The cases included 26 women who had a unilateral invasive carcinoma and 35 women undergoing prophylactic oophorectomy for a family history of ovarian cancer. As predicted by previously developed models, epithelial inclusion cysts were identified more frequently with advancing age in both cases and controls. However, the mean and maximum number of cysts per slide in a woman were not increased among cases. Surface epithelial "atypia," a designation based on a composite impression of multiple features, was found in 13% of cases compared with 3% of controls (relative risk 7.1; 95% confidence interval, 1.9 to 26.1), but this result was based on small numbers. None of the other histologic features examined was found more often in cases following age-adjustment. Reexamination of sections with well-preserved surface epithelium or inclusion cysts under oil immersion demonstrated several differences in the detection of specific features between cases and controls and increased detection of "atypia" among cases, but none of these findings reached statistical significance. It is concluded that there may be subtle differences in the surface epithelium of ovaries predisposed to developing cancer as compared with controls, but these changes are difficult to identify reliably with light microscopy. Future etiologic studies should attempt to optimize specific handling and include molecular studies and epidemiologic analyses.

Adult↗
PubMed1998

Population-based study of risk of breast cancer in carriers of BRCA2 mutation.

BACKGROUND: Estimates of an 80-90% risk of breast cancer for carriers of germline mutations in the BRCA1 and BRCA2 genes are based on studies of families at high risk of breast cancer. Risk estimates for a population are possible if the mutation status of a representative sample of that population can be assessed. In Iceland, one common founder BRCA2 mutation occurs in 0.6% of the population. Iceland has a population-based cancer registry and a large collection of pedigrees, and estimation of cancer risk in mutation carriers is therefore possible. METHODS: We studied 575 breast-cancer patients, 541 women and 34 men unselected for family history of breast cancer. Data on cancer in first-degree relatives were available from the cancer registry. Risk of cancer was estimated by comparing the history of cancer in first-degree relatives of carriers and non-carriers. FINDINGS: 56 (10.4%) of the 541 women and 13 (38%) of the 34 men carried the 999del5 mutation. The estimated risk of breast cancer at age 50 for all female carriers of the 999del5 mutation was 17.0% (95% CI 9.1-25.9) and 37.2% (22.4-53.9) at age 70. INTERPRETATION: The results of our population-based study show that the mean risk of breast cancer in carriers of mutation in BRCA2 is lower than previously suggested. Individual risk assessment will, however, have to take account of family history.

Aged↗
PubMed1998

The kin-cohort study for estimating penetrance.

A cross-sectional study may be more feasible than a cohort or case-control study for examining the effect of a genetic mutation on cancer penetrance outside of cancer families. The kin-cohort design uses volunteer probands selected from a population with a relatively high frequency of the mutations of interest. By considering the cancer risk in first-degree relatives of mutation-positive and -negative probands as a weighted average of the risk in carriers and noncarriers, with weights calculated assuming a known mode of inheritance, one can infer the penetrance of the mutations. The estimates of penetrance by age 70 years for three specific mutations in the BRCA1 and BRCA2 genes common among Ashkenazi Jews for the first occurrence of breast or ovary cancer is 63%. The kin-cohort design can be a useful tool for quickly estimating penetrance from volunteers in a setting in which the mutation prevalence is relatively high.

Adult↗
PubMed1998

Cancer risk in women exposed to diethylstilbestrol in utero.

CONTEXT: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. OBJECTIVE: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. DESIGN: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. PARTICIPANTS: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. MAIN OUTCOME MEASURES: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. RESULTS: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. CONCLUSIONS: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Adenocarcinoma, Clear Cell↗
PubMed1998

The APCI1307K allele and cancer risk in a community-based study of Ashkenazi Jews.

Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer (CRC). APC is a tumour-suppressor gene, and somatic loss occurs in tumours. The germline T-to-A transversion responsible for the APC I1307K allele converts the wild-type sequence to a homopolymer tract (A8) that is genetically unstable and prone to somatic mutation. The I1307K allele was found in 6.1% of unselected Ashkenazi Jews and higher proportions of Ashkenazim with family or personal histories of CRC (ref. 2). To evaluate the role of I1307K in cancer, we genotyped 5,081 Ashkenazi volunteers in a community survey. Risk of developing colorectal, breast and other cancers were compared between genotyped I1307K carriers and non-carriers and their first-degree relatives.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up.

OBJECTIVES: To extend the follow up of a cohort of 14,457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. METHODS: The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex and calendar time. RESULTS: In the combined follow up period (1952-90), mortality from all causes and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and 96, respectively). Significant excesses occurred for ischaemic heart disease (SMR 108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and cancer of the central nervous system (SMR 64). Workers exposed to trichloroethylene showed non-significant excesses for non-Hodgkin's lymphoma (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and bone (RR 2.1). None of these cancers showed an exposure-response gradient and RRs among workers exposed to other chemicals but not trichloroethylene often had RRs as large as workers exposed to trichloroethylene. Workers exposed to solvents other than trichloroethylene had slightly increased mortality from asthma, non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. CONCLUSION: These findings do not strongly support a causal link with trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and non-Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence.

Asthma↗
PubMed1997

The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.

BACKGROUND: Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area. METHODS: We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers. RESULTS: One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated. CONCLUSIONS: Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families.

Adult↗
PubMed1997

Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma.

OBJECTIVE: To investigate the relationship of number and type of nevi to the development of melanoma. DESIGN: Case-control study. SETTING: Outpatient clinics in referral hospitals. PATIENTS: Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus. MAIN OUTCOME MEASURES: Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners. RESULTS: Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma. CONCLUSIONS: Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention.

Adult↗
PubMed1996

Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/Cancer Study Group.

BACKGROUND: In recent years, brain lymphoma incidence has dramatically increased, presumably because of elevated risk of brain lymphoma among persons with acquired immunodeficiency syndrome (AIDS). PURPOSE: The objective of this study was to estimate independent incidence and survival rates of brain lymphoma among persons with or without AIDS and to understand the epidemiologic features of this cancer. METHODS: We linked AIDS and cancer registry reports at nine state and local health departments and compared the demographics, histology, and survival of brain lymphoma cases among persons with or without AIDS. The data were limited to people under 70 years of age. We calculated the incidence of brain lymphoma among persons with AIDS and compared observed cases with those expected. The differences were statistically analyzed using the Poisson test. Epidemiologic features of brain lymphoma in persons with or without AIDS were compared using the chi-squared test, the Student's t test, and the chi-squared test for linear trend. The logrank test was used to compare survival rates estimated by the Kaplan-Meier technique. All P values were two-sided. RESULTS: We matched 50,989 AIDS registry reports to 859,398 cancer registry reports (data from 1981 to 1990) and found 431 people with both AIDS and brain lymphoma. Among people with AIDS, those developing brain lymphoma versus those without brain lymphoma were more likely to be white (70% versus 59%; P < .001) and had homosexuality as their only human immunodeficiency virus risk factor (75% versus 64%; P < .001). Of the 431 patients, 223 developed brain lymphomas during 47,465 person-years of observation after diagnosis of AIDS. The absolute incidence rate of brain lymphoma among persons with AIDS was 4.7/1000 person-years (95% confidence interval = 4.1-5.3/1000 person-years), 3600-fold higher than the base-line rate in the general population. From 1980 through 1989, overall counts of brain lymphoma increased ninefold. Most of this increase was derived from persons with AIDS, but a substantial increase also occurred among persons without AIDS (0.04/100,000 in 1982 to 0.28/100,000 in 1989) (chi-squared test for trend; P < .05). The median survival was shortest for persons with AIDS and brain lymphoma (2 months), was intermediate for persons with brain lymphoma without AIDS (5-7 months), and was longest for persons with AIDS without brain lymphoma (14 months) (P < .05 for all comparisons). CONCLUSIONS: This analysis distinguishes the separate epidemiologies of brain lymphoma incidence among persons with or without AIDS and shows brain lymphoma incidence among persons with AIDS to be several thousand-fold higher than that in the general population. The study documents the overwhelming effect of AIDS-associated brain lymphoma on the overall rate in the general population and demonstrates a significantly rising trend, although of a lesser magnitude, among persons without AIDS. IMPLICATIONS: This study emphasizes a greater need to bring health care resources to this burgeoning epidemic.

Adult↗
PubMed1995

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

Adolescent↗
PubMed1995

Ovarian cancer, ovulation and side of origin.

Reports of more right-sided ovarian cancers and more ovulations in the right ovary seemed to offer powerful support for the theory that ovulation, per se, leads to ovarian cancer risk. We examined laterality in 25,692 epithelial ovarian cancers diagnosed in 1973-89 included in the US Surveillance, Epidemiology, and End Results system of cancer registries. Ovarian cancer occurred equally often in the left and right ovaries in this large series of incident cases.

Aged↗