Vaginal cancer in a woman with a family history of ovarian cancer

The proband was referred to familial ovarian cancer surveillance because two of her sisters died of carcinoma of the ovary. Her third sister succumbed of cervical cancer and her brother had acute myeloblastic leukaemia. Her second brother is alive and healthy. None of her parents and their sibs suffered of malignant disease. The offspring of the proband's sibs are young and appear to be normal. During surveillance she developed a stage I vaginal cancer. Following preoperative brachytherapy she underwent a radical hysterectomy and bilateral salpingoophorectomy with pelvic lymphadenectomy, and she is free of disease during 2 years of follow-up. The authors are not aware of any similar case.     

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.     

Risk factors for breast cancer in women with a breast cancer family history

For the study of the relationship of the pelviureteric system of one kidney to that of the contralateral one, bilateral cutaneous ureterostomy was performed in 14 dogs. The renal pelvis (RP) and ureter (U) of one side were distended separately with a balloon filled with saline in increments of 1 and 0.25 ml, respectively, and the pressure response of the contralateral RP and U was recorded. The test was repeated after anesthetization of the RP and U. RP distension with 1 ml of saline effected a pressure rise (P < 0.05) in the ipsilateral RP but no pressure response in the ipsilateral U or the contralateral RP or U (P > 0.05). RP distension with 2, 3, and 4 ml of saline induced a significant pressure rise in the ipsi- and contralateral RP but not in the ureters. Ureteric distension produced a pressure elevation (P < 0.05) on the ipsilateral U but had no effect on the contralateral U (P > 0.05) or on either of the renal pelves (P > 0.05). Distension of the anesthetized RP or U effected no pressure response in any of the ipsi- or contralateral RPs or Us. In conclusion, distension of the RP with large volumes led to an increase in pressure in the contralateral RP but not in the U. A reflex relationship is postulated to exist between the two renal pelves and to be mediated through a reflex we call the reno-renal pelvic reflex. It seems that this reflex acts to allow either of the kidneys to share an extra load of the other one by increasing the contractile activity of the RP, thus assumedly assisting the regulation of urine flow.     

Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer

BACKGROUND: Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS: We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS: We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.     

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer

BACKGROUND: The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). METHODS: We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. RESULTS: HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. CONCLUSIONS: The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.     

Screening women aged less than 50 years with a family history of breast cancer

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.     

Frequency of replication errors in colorectal cancer and their association with family history

In the Czech Republic, the incidence of Lyme borreliosis (LB) has shown a rising trend since 1988. The goal of this study has been to find out to what extent a selected part of population is aware of ticks and of the relationship between ticks and LB. The study was based on a questionnaire survey. A total of 110 respondents were selected, including 19 secondary school students, 32 blood donors, 44 park-goers, 15 countryside people. As many as 99% of the respondents were aware of the presence of ticks, 91% knew that ticks are sucking blood of humans and animals, 1.8% thought they eat leaves. 74.5% of the respondents expect ticks to reach them from the vegetation while 22% believe that ticks fall from the trees. Furthermore, 87% and 75% of the respondents indicated to have had ticks attached to the skin or to have removed a tick from other persons' skin, respectively. Only 6.7% of them had never come into contact with ticks. 17% of the respondents use disinfectant when removing a tick, while 67% use oil for tick removal. Almost 30% remove ticks with naked hands. Over 14% destroy the ticks by squashing them with naked fingers. Finally, about 11% of the population studied had never heard about LB and 41% were not aware of the risk of tick-borne encephalitis.     

The family history component of cancer genetic risk counseling

This study evaluated effective resistances on the ventricular surfaces of arterially-perfused rabbit hearts. Effective resistances were determined with a four-electrode array that was parallel or perpendicular to epicardial fibers. Resistance along or across epicardial fibers was determined by applying current to the epicardium with two parallel line electrodes and measuring potentials in the region between the electrodes. Computer simulations were performed to gain insight into the distribution of current in the ventricular wall. The effective resistances were not different along versus across fibers. Simulations showed that transmural rotation of fibers causes current to be distributed differently when the electrode is oriented perpendicular versus parallel to epicardial fibers. When the array is oriented so that epicardial current is across fibers, the fraction of current that flows transmurally and along the deeper fibers increases while the fraction of current that flows epicardially decreases. This introduces isotropy of the effective resistance. Thus, in contrast to isolated cardiac fibers, the ventricular epicardium exhibits isotropic effective resistance due to transmural rotation of fibers. The rotation and isotropic resistance may be important for cardiac electrical behavior and effects of electrical current in the ventricles.     

Lifestyle intervention in overweight individuals with a family history of diabetes

OBJECTIVE: To assess the effect of lifestyle intervention over 2 years on changes in weight, coronary heart disease (CHD) risk factors, and incidence of diabetes in overweight individuals with a parental history of diabetes. RESEARCH DESIGN AND METHODS: Participants (n = 154), who were 30-100% over ideal body weight, had one or both parents with diabetes, and were currently nondiabetic, were randomly assigned to 2-year treatments focused on diet (decreasing calories and fat intake), exercise (goal of 1,500 kcal/week of moderate activity), or the combination of diet plus exercise or to a no-treatment control group. Subjects were reassessed at 6 months, 1 year, and 2 years. RESULTS: At 6 months, the groups differed significantly on measures of eating, exercise, and fitness; weight losses in the diet and diet-plus-exercise groups were significantly greater than in the exercise and control conditions. Weight losses were associated with positive changes in CHD risk factors. After 6 months, there was gradual deterioration of behavioral and physiological changes, so that at 2 years, almost no between-group differences were maintained. Differences between groups in risk of developing diabetes were of borderline significance (P = 0.08). Strongest predictors were impaired glucose tolerance at baseline, which was positively related to risk of developing diabetes, and weight loss from baseline to 2 years, which was negatively related; in all treatment groups, a modest weight loss of 4.5 kg reduced the risk of type 2 diabetes by approximately 30% compared with no weight loss. CONCLUSIONS: Although initially successful, the interventions studied here were not effective in producing long-term changes in behavior, weight, or physiological parameters. However, weight loss from 0 to 2 years reduced the risk of developing type 2 diabetes. Since modest weight loss significantly reduced risk of type 2 diabetes, further research is needed to determine how best to increase the percentage of subjects achieving at least a modest weight loss.     

Distress, personality, and mammography utilization among women with a family history of breast cancer.

The authors examined the impact of psychological distress and the personality construct of conscientiousness (as measured by the Neuroticism, Extraversion, and Openness—Five Factor Inventory) on mammography utilization among women who were at increased risk for breast cancer. Participants were 200 women who had at least 1 first degree relative with breast cancer. Overall, 80% of the participants had obtained a mammogram in the previous year. Analyses controlling for potential confounders (perceived risk, decisional balance, and physician recommendation for mammography), revealed that distress was negatively associated with mammography utilization among participants who were low in conscientiousness. Distress was not significantly related to mammography utilization among highly conscientious women. The results are discussed in terms of their implications regarding interventions designed to increase mammography utilization in this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.     

Psychiatric family history in adolescents with severe asthma

OBJECTIVE: To examine the hypothesis that an association exists between severe asthma and familial affective and anxiety disorders. METHOD: A parent, usually the mother, of 62 adolescents admitted to a tertiary care asthma center was administered the Family History-Research Diagnostic Criteria Interview. Lifetime prevalence rates of psychiatric disorders in first-degree relatives were compared with previously reported rates. RESULTS: In relatives of asthmatic adolescents, rates for depression, mania (females only), substance abuse (males only), and antisocial personality disorder were significantly higher than the rates in the non-ill comparison sample. Rates for substance abuse (males only) and antisocial personality disorder were higher than the rates for relatives of the depressed comparison sample. Rates for anxiety disorders were not higher than rates in epidemiological samples. Rates of attention-deficit hyperactivity disorder (females only) and posttraumatic stress disorder in relatives were higher than in community samples. CONCLUSIONS: These results support the presence of a link between severe asthma and familial affective disorders, posttraumatic stress disorder, antisocial personality disorder, and substance abuse. Whether these disorders are genetically associated with asthma or represent an association with severe asthma because of environmental effects on the growing child is discussed.     

Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment

An investigation was made of daytime plasma prolactin levels in three groups of women aged 50 to 64 years: (1) 139 women with a family history of breast cancer; (2) 50 women on Rauwolfia treatment for hypertension, and (3) 90 women of a control group. A significant difference in prolactin levels was found between groups 2 and 3 but not between 1 and 3. These findings are considered in relation to the results of a breast cancer screening programme in which the women took part. Here, it was the women with a family history of breast cancer who showed an increased breast cancer risk, whereas the risk in women on Rauwolfia was not significantly higher than expected on the basis of the experience among controls. It is concluded that the role of prolactin in the etiology of breast cancer is still not clear.     

Baroreceptor reflex function in young normotensive men with a family history of hypertension

The purpose of this study is to evaluate the baroreflex function using lower body negative pressure (LBNP) and neck suction in young normotensive men with or without a family history of hypertension. Twenty-two young normotensive men with a family history of hypertension (FH+) and eight young normotensive men who had no family history of hypertension (FH-) were studied. FH(+) consisted of men who had a family history of hypertension within second degree relatives. We studied cardiopulmonary baroreflex function using LBNP and carotid sinus baroreflex function using neck suction and evaluated the reflex function under stimulated conditions using both LBNP and neck suction at the same time. Systolic arterial pressure (SAP)(F = 5.42, p < 0.0001) and pulse pressure (PP)(F = 15.57, p < 0.0001) decreased similarly in both groups in response to LBNP. SAP and PP responses to LBNP were not significantly affected by the family history of hypertension. Diastolic arterial pressure (DAP) increased (F = 2.89, p < 0.005) in both groups. There was a relationship between the LBNP level and family history of hypertension (F = 2.53, p < 0.013), and the increment in DAP during LBNP -30, -40 mmHg was larger in the FH(+) group. Through mean arterial pressure (MAP) was not effected by LBNP, there LBNP level was related to the family history of hypertension (F = 2.23, p < 0.02). Heart rate increased progressively (F = 25.7, p < 0.0001) with increasing levels of LBNP; however, these changes did not differ significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.     

Abnormal bcl-2 and pRb expression are independent correlates of radiation response in muscle-invasive bladder cancer

The objective of this study was to determine whether the overexpression of bcl-2, a key protein governing the apoptotic response to radiation, adds to pRb status in estimating the propensity for radiation response in patients with muscle-invasive bladder cancer. Archival formalin-fixed, paraffin-embedded, pretreatment bladder tumor samples were available in 109 of 301 patients treated preoperatively with 50 Gy in 25 fractions followed by radical cystectomy 4-6 weeks later. Radiation response was assessed by clinical-to-pathological tumor downstaging or upstaging. Altered expression of bcl-2 (47% of 107 patients), p53 (56% of 109 patients), and pRb (30% of 98 patients) was assessed by immunohistochemical staining. Morphological criteria were used to calculate the percentage of apoptotic cells. bcl-2 staining correlated with tumor grade; all grade 2 tumors (n = 7) displayed normal bcl-2 expression (negative staining). No correlations between bcl-2 staining and pretreatment apoptosis levels, p53 staining, and pRb staining were observed. In terms of the radiation response parameters, univariate analyses revealed that bcl-2 overexpression was the only factor associated with upstaging. The main predictor of downstaging was the loss of pRb expression (negative staining). Multivariate logistic regression confirmed these findings and also showed that normal pRb expression (positive staining) was significantly related to upstaging. Patient outcome was adversely affected by bcl-2 overexpression, because these patients experienced significantly increased actuarial local failure rates. No difference in distant metastasis or survival rates by bcl-2 staining was seen. The strongest independent correlates of radiation response thus far identified in muscle-invasive bladder cancer are from bcl-2 and pRb immunohistochemical staining. The overexpression of bcl-2 and the normal expression of pRb seem to thwart the apoptotic response to radiation via independent mechanisms. Abnormalities in the expression of proteins that regulate apoptosis may prove to establish a molecular phenotype to characterize which patients should receive radiotherapy.     

A prospective study of family history and the risk of colorectal cancer

BACKGROUND: A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. METHODS: We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. RESULTS: The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, < 0.001). CONCLUSIONS: A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people.