Features of the spike activity of globus pallidus neurons and pallido-thalamic functional interactions during targeted verbally cued movements in humans

OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in women with various categories of family history. DESIGN: A meta-analysis of all published case-control and cohort studies. METHODS: Pooled relative risk estimates were calculated for the case control studies, using the Mantel-Haenzel method. These estimates were combined with the relative risks from the cohort studies. The pooled estimates of relative risk were used to estimate lifetime risks of ovarian cancer from age 15 up to age 75, for various categories of family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of developing ovarian cancer were calculated for the categories of women with 1. an affected first degree relative; 2. an affected mother; 3. an affected sister; and 4. women with more than one affected relative. RESULTS: The relative risk to first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this relative risk declines with age. The relative risk to mothers of cases 1.1 (95% CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1), and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a substantially higher risk of developing ovarian cancer compared with women without such a history. However the risk is small for most categories of family history, except for the small number of individuals who have more than one affected relative.     

Cancer in developing countries: Part II--Cancer control: strategies and priorities

In 1992 the first Hereditary Cancer Center in Poland has been organized in Szczecin. DESIGN: One of its goals is application of appropriate management in families with hereditary ovarian cancer. The aims of our program include studies of: incidence, clinical characterization, DNA diagnostic tests and efficiency of screening for early detection of hereditary ovarian tumors in North-West Poland. MATERIAL: Our program includes 234 families with 258 cases of ovarian cancers. RESULTS: Site-specific familial aggregation of ovarian cancer was diagnosed in 16 (6.84%) families, breast-ovarian cancer syndrome in 27 (11.54%), Lynch II syndrome in 5 (2.14%) families, undefined cancer family aggregation in 12 (5.13%) families, sporadic ovarian cancers diagnosed age of 44 in 56 (23.93%) families and other sporadic ovarian cancers in 118 (50.4%). In 17 patients with ovarian cancer from families with breast-ovarian cancer syndrome constitutional BRCA-1 gene mutations were studied by sequencing DNA on automated sequencer of PCR products for all 24 exons. In 1 patient constitutional mutation in exone 11 was detected. We found also multiply polymorphic changes. 124 women-members of 116 families with diagnosed hereditary predisposition for ovarian cancer have been studied for asymptomatic tumors by intravaginal USG and evaluation of CA 125 marker every 6 month beginning from 20-25 years of age. Up to now we found 5 cases of benign serous cystadenomas, 3 cases of cystadenomas of borderline malignancy and 1 cases of serous cystadenocarcinoma. CONCLUSIONS: It seems, that particular surveillance program in women from families with hereditary cancers can be the effective way of detection of early ovarian tumors. Clinical characterization of hereditary ovarian cancers in North-West Poland and other countries is similar.     

The role of diet for development of renal cell carcinoma]

Dietary risk factors for renal cell cancer were investigated in a population based case-control study of incident cases. A total of 351 cases and 340 controls matched for age and sex were interviewed about dietary habits as well as exposure to other known or suspected risk factors. An association was found between risk of renal cell cancer and energy intake, especially fats. There was no protective effect of fruits but a weak protective effect of cruceferous vegetables. The association with diet was present after adjusting for the effect of cigarette smoking, socioeconomic status and body mass index, all of which have been identified as risk factors for renal cell cancer.     

Biochemical composition of human peripheral arteries examined with near-infrared Raman spectroscopy

OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familial IIM were compared with those in 181 patients with sporadic IIM. The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 2 families with inclusion body myositis. RESULTS: The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002). CONCLUSION: These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM.     

Evaluation of an immunoturbidimetric assay for haemoglobin A1c on a Cobas Mira S analyser

A case-control study was carried out in Spain to assess associations between parity, lactation and age at first full-term pregnancy and breast cancer. From November 1989 to February 1992, 184 incident breast cancer histologically confirmed cases were interviewed and matched by age and residence to 184 hospitalized patients and 184 community controls selected by random digit dialing. Multiple logistic regression was used to assess the independent influence of each factor on the risk of breast cancer in relation to other factors included in the model. Age at first full-term pregnancy was associated with breast cancer risk with an estimated odds ratio of 3.5 (95% CI 1.41-9.83) for women with their first birth after 30 years in comparison with those whose first birth was before age 21. Breast cancer risk decreased with increasing number of full-term pregnancies, OR 0.3 (95% CI 0.16-0.78) for women who had had more than 3 full-term pregnancies in comparison with nulliparous women. Among parous women, the estimated OR for women with more than 3 children was 0.4 (95% CI 0.13-0.81) after allowance for age at first childbirth and lactation. The estimated OR was 2.6 (95% CI 1.4-4.7) for women with a positive history of breast cancer in first-degree relatives. Breast cancer was not associated with total duration of lactation. The study indicates that parity is an independent risk factor associated to breast cancer and that the women with a late age at first full-term pregnancy constitute a high-risk group.     

Nucleic acid technology (NAT) testing and the transfusion service: a rationale for the implementation of minipool testing

Breast cancer is the single largest cancer and causes the high rate of cancer mortality among women. A positive family history of breast cancer is recognized as one of the major risk factors for this disease. The present study evaluates bleomycin (BLM)-induced chromosome sensitivity analysis in breast cancer families which provides indirectly a measure of the DNA repair defect of each person. BLM sensitivity assay on cultured lymphocytes of 36 familial breast cancer patients, their 85 first or second degree female relatives, 36 sporadic breast cancer patients and 40 age- and sex-matched controls (without any family history of cancer) were carried out to measure interindividual variation in their DNA repair capacity through mutagen-induced chromosome sensitivity analysis. Fifty percent of familial breast cancer patients and seven unaffected relatives showed hypersensitivity. Compared to hyposensitive relatives these seven subjects may be considered as high risk individuals.     

Characteristics of women with a family history of ovarian cancer. I. Galactose consumption and metabolism

BACKGROUND: Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS: The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype. RESULTS: Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. CONCLUSION: Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.     

Inheritance in idiopathic premature ovarian failure: analysis of 71 cases

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.     

Familial predisposition for degenerative disc disease. A case-control study

STUDY DESIGN: This case-control study was undertaken to determine if relatives of patients who had been admitted for surgery for degenerative disc disease-related problems were at increased risk for lower back pain or sciatica. OBJECTIVES: To determine if familial factors play a role in placing a person at risk for development of degenerative disc disease of the lumbar spine. SUMMARY OF BACKGROUND DATA: It is known that smoking and various occupational factors can place a person at risk for degenerative disc disease problems. It is not known if a familial predisposition may also exist. METHODS: The family members and relatives of 65 patients who had undergone surgery for lumbar degenerative disc disease were interviewed with a standardized questionnaire and compared with a control group of 67 patients who had been admitted to hospital for non-spine-related orthopedic procedures. The same interview and standardized questionnaire was used for both groups by a single observer. RESULTS: In the study group of 65 patients who had undergone surgery for degenerative disc disease, 44.6% were noted to have a positive family history, whereas 25.4% of the patients in the control group had a positive family history. Eighteen and one-half percent of relatives in the study group had a history of having spinal surgery, compared with only 4.5% of the control group. CONCLUSIONS: The results indicate that a familial predisposition to degenerative disc disease can exist along with other risk factors.     

Familial clustering of obesity and breast cancer

One of the most striking characteristics of breast cancer (BC) is a tendency to familial aggregation. In order to evaluate whether familial clustering of obesity could account, at least in part, for the familial aggregation of BC, we compared the adult body size of entire sets of first-degree relatives belonging to 60 families with two or more cases of BC (case families) and 120 BC-free families (control families). Case families included an index case recently admitted for primary BC who had a confirmed first-degree family history for the disease. Control families included one population-based healthy index control with no family history and age-matched (2:1) to index cases. Index cases and controls, recruited from a pool of participants in a large case-control study, completed a questionnaire covering their own body size history as well as that of each of their first-degree relatives (598 case and 1,128 control relatives) using a validated system of body silhouette drawings. The odds ratio (OR) for premenopausal familial BC associated with having one parent markedly obese compared to none was 0.17 (95% confidence interval [CI] 0.04-0.65), while having both parents obese resulted in an OR of 0.25 (95% CI 0.04-1.56). Obesity among siblings was not related to premenopausal familial BC risk nor was familial obesity a significant predictor of familial BC after menopause. Index cases from both menopausal groups tended to be thinner than their unaffected relatives at age 40 years and thereafter. The inverse relationship between parental obesity and premenopausal BC risk is concordant with the protective effect of obesity on early-onset BC previously reported at the individual level.     

Risk of leukemia after platinum-based chemotherapy for ovarian cancer

BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.     

Lack of familial clustering of hepatitis C virus infection

BACKGROUND: Although transmission of hepatitis C virus (HCV) through parental exposure is well documented, it is still controversial whether familial clustering of HCV occurs. METHODS: To investigate risk factors for HCV infection, 109 cases and 84 non-infected controls were studied. In addition, 250 family members (104 men, 146 women) of cases and 170 family members of controls (64 men, 106 women) were tested for HCV infection using an anti-HCV antibody, alanine aminotransferase (ALT), and reverse transcribed polymerase chain reaction (RT-PCR). RESULTS: In the case-control analysis, people aged > or =60 were almost three times more likely to be infected by HCV than those aged <40. Risk of HCV infection was most strongly related to a history of blood transfusion (OR = 12.6, 95% CI: 4.3-36.5) followed by a history of jaundice (OR = 4.1, 95% CI: 1.3-12.6). Only one family member of cases and no-one related to the controls had HCV infection. CONCLUSIONS: These results suggest that, in Korea, age and parenteral exposure, such as a blood transfusion, are risk factors for HCV infection and familial clustering of HCV infection, if it occurs, is rare.     

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk

PURPOSE: Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS: Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION: Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.     

Symptom-related self-care of Mexican Americans with type 2 diabetes: preliminary findings of the Starr County Diabetes Education Study

OBJECTIVES: Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored. Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. METHODS: We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States. Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. RESULTS: Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR] = 1.05). Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems (ORage 35+ :age <20 = 1.13, 95 percent confidence interval [CI] = 0.7-1.9), but a relatively strong association among women with fertility problems (ORage 35+ :age <20 = 2.96, CI = 1.3-7.0). Among women with a first full-term birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. CONCLUSIONS: Our study suggests that the association between late age at first birth and breast cancer is stronger among women with self-reported fertility problems than among women with no fertility problems.     

Relationship between number of ovulatory cycles and accumulation of mutant p53 in epithelial ovarian cancer

BACKGROUND: It has been suggested that increased numbers of ovulations might increase the risk of p53 gene (also known as TP53) mutation in the ovarian epithelium, thereby leading to the development of cancer. The data supporting this hypothesis have come from an observation that accumulation of p53 protein in epithelial ovarian cancer was strongly associated with increasing numbers of ovulatory cycles. We have further investigated the association between ovulatory history and p53 gene mutation by use of data from a large case-control study of ovarian cancer in Australia. METHODS: Tissue blocks were available for immunohistochemical analysis of p53 protein from 234 case subjects, aged 18-79 years, who had invasive epithelial ovarian cancer. Epidemiologic data were also available for these women and for 855 control subjects. Case-case comparisons were made by use of prevalence ratios and 95% confidence intervals (CIs), and case-control comparisons were made by use of odds ratios (ORs) and 95% CIs. All statistical tests were two-sided. RESULTS: There was no association between p53 accumulation and years of ovulation. Women with p53-positive cancers had undergone an average of 29.3 years of ovulation compared with 29.0 years of ovulation for women with p53-negative cancers (P=.8). Although the overall risk of ovarian cancer development was significantly increased in women who had undergone more years of ovulation (OR=2.17; 95% CI =1.54-3.05-for > or =35 years versus <23 years of ovulation), there was no difference in the risk associated with p53-positive and p53-negative cancers. CONCLUSIONS: These results confirm the association between increased ovulation and ovarian cancer risk but do not support the hypothesis that this association is due to an increased risk of p53 mutation with a greater number of ovulatory cycles.     

Use of screening mammography and its demographic and risk determinants in women 25 to 65 years of age

BACKGROUND: To know the utilization of the screening mammography among women from 25 to 65 years old in an urban health zone, where there is not an specific screening program for breast cancer. To detect the demographic and risk determinants that are involved in the mammography screening use. SUBJECTS AND METHODS: A sample of 1,240 women were interviewed consecutively as they visited their physician. Risk factors, sociodemographic variables and use of health services were analyzed. The associated variables with the use of mammography screening were determined by univariant analysis. A multiple logistic regression model was designed to identify the variables independently associated with the use of mammography screening. RESULTS: The percentage of interviewed women who have completed at least one mammography screening in the last three years has been 10.2 +/- 3% (confidence level: 95%), 68.3% of them were under 50 years old. The variables independently associated with the use of mammography screening were: age (OR = 1.08); routine visit to the gynecologist (OR = 8.13); educational level (primary: OR = 2.44, secondary: OR = 3.66, university: OR = 7.43, no schooling: reference level); and knowledge about the benefits of mammography screening (OR = 6.15). Family history of breast cancer and the other risk factors were found not to be associated with the use of mammography screening. CONCLUSIONS: The use of mammography screening among women from 25 to 65 years is inadequate according to the age and other risk factors. Mammography screening among women with a family history of breast cancer and those over 50 years old is underused, so it would be recommended and their use increased for these women. But women under 40 years old without family history of breast cancer have to be dissuaded from undertaking such a screening.     

Breast cancer risk and alcohol consumption: results from a large case-control study

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.     

Dietary factors and lung cancer among men in west Sweden

BACKGROUND: Previous studies have reported an association between tea drinking and lung cancer. In view of these data, the relationship between tea drinking as well as other dietary factors and lung cancer was investigated in a case-control study in the west of Sweden. METHODS: Patients with suspected lung cancer were collected from pulmonary units at central hospitals in the area investigated, and population controls were matched for age. The material reported here comprises 308 male cases with a confirmed diagnosis of lung cancer and 504 controls. The participants were interviewed by specially trained nurses, using a questionnaire to assess smoking, dietary habits, occupational exposures and conditions in the residential area (local air pollution). This paper reports the results from dietary factors studied with a food frequency technique. RESULTS: The results demonstrated a strong protective effect of vegetables (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.46-1.05, and OR = 0.37, 95% CI: 0.23-0.61 for intermediate and high consumption classes respectively). A low OR was consistent for all histological types of lung cancer. High consumption of fruits did not show any similar protective effect. Drinking milk was associated with a dose-response related risk increase after adjustment for smoking and vegetable consumption (P for trend = 0.07). Odds ratio was 1.73, 95% CI: 1.00-3.01 for high consumption of milk. CONCLUSIONS: High intake of vegetables had a strong protective effect among males. Diet is thus a potential confounding factor in studies on lung cancer and environmental factors and should thus be taken into consideration in the planning of such studies.     

Treadmill exercise duration and dyspnea recovery time in chronic obstructive pulmonary disease: effects of oxygen breathing and repeated testing

OBJECTIVES: To evaluate biochemical outcome after definitive radiotherapy as a function of family history groupings. METHODS: Biochemical freedom from disease for 920 men treated for prostate cancer with external beam radiation alone between March 1987 and December 1997 was compared according to hereditary/familial history (PFH) and sporadic family history. To adjust for known predictors of biochemical outcome, 97 PFH patients were randomly matched 2:1 to 194 sporadic patients according to age, grade, pretreatment prostate-specific antigen level, and palpation stage and compared in terms of biochemical outcome. Cox multivariate regression analyses were also performed to identify independent predictors of outcome in the two patient populations. RESULTS: In both patient populations, univariate analysis of biochemical outcome demonstrated no difference according to family history groupings. After adjusting for known predictors of biochemical outcome, multivariate analysis confirmed the nonsignificant univariate findings. CONCLUSIONS: No difference was found in this study between patients with a PFH (combined hereditary and familial) and patients with the sporadic form of prostate cancer. Recent published reports are conflicting and the question of whether a genetic change influencing prostate cancer causation is associated with factors altering treatment response should be addressed using a multi-institutional, carefully documented, prospective family history data collection and outcome analysis.     

Population attributable fraction estimation for established breast cancer risk factors: considering the issues of high prevalence and unmodifiability

Established breast cancer risk factors, in addition to being relatively unmodifiable, are highly prevalent among US women. Previous reports of population attributable fraction for the established risk factors have used definitions that resulted in 75-100% of women in the source population labeled exposed. The practical value of such estimates has not been discussed; further, the estimates have frequently been misinterpreted. In the context of examining the interpretation and public health value of such estimates, the authors demonstrate the sensitivity of the population attributable fraction to changes in exposure cutpoints. They use data from the Carolina Breast Cancer Study, a case-control study of breast cancer conducted in North Carolina between 1993 and 1996. For the four established risk factors (menarche before age 14 years, first birth at age 20 years or later/nulliparity, family history of breast cancer, and history of benign breast biopsy), the estimated population attributable fraction was 0.25 (95% confidence interval 0.06-0.48). Over 98% of the source population was exposed to at least one of these risk factors. The population attributable fraction estimate was reduced to 0.15 when more restrictive definitions of early menarche (less than age 12 years) and late age at first full-term pregnancy (30 years or more) were used (proportion exposed, 0.62). Population attributable fractions for established breast cancer risk factors probably have little public health value because of both the high proportions exposed and the relative unmodifiability of the risk factor distributions.