遗传性非息肉病性结肠直肠癌的家系和临床研究

目的：探索遗传性非息肉病性结肠直肠癌（hereditary nonpolyposis colorectal cancer,HNPCC)家族成员的发病规律和临床特征，寻求简单，有效的筛查和防治方法。方法：调查家族史，分析9例成员的染色体脆性部位（fragile site,FS)和11例患者的临床资料。结果：先证者祖父两次婚配，祖父母子孙发病接近1／2，5例祖父母后代和5例HNPCC患者FS检出率均为80％（4／5），总检出率为56％（5／9），HNPCC患者11人共发生15例次癌，Lynch综合症Ⅱ型和多原发癌各3例，占27％（3／11），同时性癌1例；病理检查显示11例次均为腺癌。手术后5年生存率88％（7／8），有3例次已生存10年以上。结论：（1）该家族呈常染色体显性遗传。（2）及早发现并经腹手术治疗效果好；（3）FS的高检出率方便了发病的预测和筛查，有助于早期诊断。     

Diagnosis and treatment of greenstick and torus fractures of the distal radius in children: a prospective randomised single blind study

Objective  

The management and the diagnostic modalities used in cases of undisplaced greenstick and torus fractures of the distal radius in children vary between different treatment centres. The aim of this study was twofold: firstly, to analyse the sensitivity of X-rays versus ultrasound to diagnose these fractures; secondly, to compare three available treatment options (plaster cast, Futuro splints, and double Tubigrip) in terms of pain, analgesia requirements, grip strength, deformity, stiffness and interference with a child’s activities of daily living.     

A clinicopathological analysis of breast cancer in patients with a family history

A study was conducted to investigate the clinical and pathological characteristics of breast cancer in patients with a family history (FH). Among 4,481 primary breast cancer patients, 394 (8.8%) had families which included two or more breast cancer patients within three generations (FH(+) group). This group was compared with the remaining 3,969 patients (FH(–) group) with the following results: (1) The tumor diameter in the FH(+) group was slightly less than that in the FH(–) group [not significant (NS)], with fewer lymph node metastases (P<0.05); (2) the positive rates for the estrogen receptor were 52% (138/266) and 49% (1,216/2,481), respectively (NS); (3) expression of the c-erbB-2 protein was observed in 14 out of 40 (35%) and 32 out of 100 cases (32%), respectively (NS); (4) the relative risk of bilateral occurrence in the FH(+) group was 1.4, with a 95% confidence interval of 0.9–2.4; (5) the 15-year survival rate was 72% and 60%, respectively, suggesting a better prognosis for the FH(+) group (P<0.01); and (6) multivariate analysis showed that the contribution of FH to postoperative survival was marginal (P=0.07). Factors related to the hormonal environment such as age at menarche (P=0.08) and age at menopause (P=0.08) made a greater but non-significant contribution to the prognosis of the FH(+) group than to that of the FH(–) group. However, further genetic and molecular biological analyses of familial breast cancer are needed in order to clarify the mechanisms of cancer accumulation within families.     

Carcinomas associated with Lynch syndrome: a family history

Lynch syndrome is a rare and inherited defect disorder. People who have Lynch syndrome are strongly predisposed to develop colorectal cancer as well as several other types of cancer. The aim of this study was to explore features of ovarian cancers arising in families with Lynch syndrome. This study was a case report based on family history examining three patients with a new diagnosis of colorectal adenocarcinoma with ovarian cancer. Family members of carriers of the mutations were counseled, and those found to be at risk were offered mutation testing. The clinical criteria of the Amsterdam II guidelines for Lynch syndrome were used in this study. This is a maternal history of a 27-year-old woman sharing the destiny of her 48-year-old mother and 45-year-old aunt, both of which were suffering from Lynch syndrome associated with ovarian cancer. The maternal grandmother and maternal uncle of this young woman also suffered from colon cancer in their forties. The medical implications for the carrier relatives were considered as the maternal branch of the family.     

Hip dysplasia in Charcot-Marie-Tooth disease: report of a family

Charcot-Marie-Tooth disease is classified into hereditary motor and sensory neuropathy (HMSN) types I and II, and affected patients present with progressive peripheral neuropathy. Some previous orthopedic studies have revealed the association of hip dysplasia with HMSN, in addition to pes cavovarus, scoliosis, and recurrent dislocation of the patella. We describe three patients from the same family who were each diagnosed as having HMSN type I with associated bilateral severe hip dysplasia, borderline abnormalities of both acetabula, and dysplastic osteoarthritis. Based on our experience with these patients and a review of previous reports, we concluded that routine screening of hip joints, especially for those with a family history of HMSN, is necessary for early diagnosis.     

A family history of fracture and fracture risk: a meta-analysis

The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.     

Metachronous colorectal cancer risk in patients with a moderate family history

Aim Lifetime risk of a metachronous colorectal cancer (mCRC) is 0.6–3% following sporadic colorectal cancer (CRC) and 15–26% in Lynch syndrome. The lifetime incidence of CRC in individuals with moderate familial risk is 8–17%. Risk of mCRC is unknown. Method A retrospective longitudinal study of the Regional Familial CRC Registry was performed. Patients who had at least one CRC were categorized as follows: moderate risk (n = 383), Lynch syndrome (n = 528) and average (population) risk (n = 409). The Kaplan–Meier estimate (1‐KM) and the cumulative incidence function were used to calculate the risk of mCRC. The 1‐KM gives the risk for individuals remaining at risk (alive) at a given time point and thus is useful for counselling. The cumulative incidence function gives the risk for the whole population. Results The 1‐KM and the cumulative incidence function demonstrated that the risk of mCRC was significantly higher in moderate‐risk patients compared with average (population)‐risk patients (1‐KM, P = 0.008; cumulative incidence function, P = 0.00097). However, the risk of mCRC was higher in patients with Lynch syndrome than in moderate‐risk or average (population)‐risk patients. The 1‐KM in moderate‐risk patients was 2.7%, 6.3% and 23.5% at 5, 10 and 20 years, respectively. In average (population)‐risk patients, the 1‐KM was 1.3%, 3.1% and 7.0% at 5, 10 and 20 years, and the cumulative incidence function was 0.3%, 0.6% and 2.4% at the same time points, respectively. Conclusion These data indicate that the risk of mCRC is significantly higher in patients with a moderate family history of CRC than in those with an average (population) risk. This justifies proactive lifelong surveillance.     

Colonoscopy in asymptomatic individuals with a family history of colorectal cancer

Background This study was performed to evaluate the use of total colonoscopy as the optimal screening test in asymptomatic individuals with a family history of colorectal cancer (CRC). Methods Colonoscopy was performed in 249 asymptomatic individuals who had one or two first-degree relatives (FDRs) with CRC; individuals with three or more FDRs with CRC were excluded. Results Eighty-six colonic lesions were found in 51 individuals (51 of 249; 20.5%). Among these 51 subjects, 27 had neoplastic polyps (n=38) and 29 had metaplastic polyps (n=44). Although no invasive cancer was detected, in 14 individuals the lesions had a high malignancy potential because of their size and histopathology. We did not confirm a statistically significant difference in the incidence of neoplastic polyps according to the number of affected FDRs. Finally, the presence of metaplastic polyps was a very strong indication for the concomitant presence of metaplastic polyps (P<.0001). Conclusions Total colonoscopy is the optimal screening procedure for the examination of asymptomatic individuals with a family history of CRC.     

Setting up a breast cancer family history clinic

Breast cancer causes around 21,000 deaths per year in the UK, the vast majority of these occurring in women aged over 50 years with no genetic predisposition to the disease. Screening and symptomatic services for these women, although by no means perfect or homogeneous, have gradually improved over the last 10 years and, perhaps as a result of this, together with increased use of adjuvant systemic therapy, mortality in this group has fallen. Despite this reassuring state of affairs, media interest in the disease and patients' perception of their risk of developing breast cancer have risen. Part of this is undoubtedly due to the new scientific developments in cancer genetics and, in particular, identification of the BRCA1 gene in 1994 and BRCA2 gene shortly afterwards. These genes are dominantly inherited with up to 80% penetrance; thus, women (and occasionally men) inherit these genes and have a high lifetime risk of developing breast cancer, usually at a younger age than average and possibly of a more aggressive phenotype. Unaffected family members can now be screened and, if they prove carriers, screening for early detection and prevention strategies such as bilateral prophylactic mastectomy can be offered. Because of the high risk of ovarian cancer in BRCA1 carriers, screening or prophylactic ovariectomy may also be considered.     

Breast-conservation therapy in early-stage breast cancer patients with a positive family history

Background Our goal was to evaluate the role of breast-conservation therapy in early-stage breast cancer patients with a family history (FH) of breast cancer. Methods Between 1970 and 1994, 1324 female patients with breast cancer were treated with breast-conservation therapy at our institution. From these, we identified 985 patients with stage 0–II breast cancer and who had available information on FH status. FH was considered positive in any patient who had a relative who had been previously diagnosed with breast cancer. Disease-specific survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. Results The stage distribution for the 985 patients was as follows: 0 in 65 (7%), I in 500 (51%), and II in 420 (43%). The median age was 50 years (range, 21–88), with a median follow-up time of 8.8 years (range, .25–29). The median tumor size was 1.5 cm. FH was positive in 31%. There were no significant differences in locoregional recurrence, distant recurrence, disease-specific survival, or incidence of contralateral breast cancer in patients with a positive FH versus patients with a negative FH. Conclusions Breast-conservation therapy is not contraindicated in early-stage breast cancer patients with a positive FH.     

Absolute risk of breast cancer for Australian women with a family history

BACKGROUND: The purpose of the present paper was to estimate the absolute risk of breast cancer over the remainder of a lifetime in Australian women with different categories of family history. METHODS: Age-specific breast cancer incidence rates were adjusted for screening effects, and rates in those with no family history were estimated using the attributable fraction (AF). Relative risks from a published meta-analysis were applied to obtain incidence rates for different categories of family history, and age-specific incidence was converted to cumulative risk of breast cancer. The risk estimates were based upon Australian population statistics and published relative risks. Breast cancer incidence was from New South Wales women for 1996. The AF was calculated using prevalence of a family history of breast cancer from data on Queensland women. The cumulative absolute risk of breast cancer was calculated from decade and mid-decade ages to age 79 years, not adjusted for competing causes of death. RESULTS: Lifetime risk is approximately 8.6% (1 in 12) for the general population and 7.8% (1 in 13) for those without a family history. Women with one relative affected have lifetime risks of 1 in 6-8 and those with two relatives affected have lifetime risks of 1 in 4-6. The cumulative residual lifetime risk decreases with advancing age; by age 60 years all groups with only one relative affected have well above a 90% probability of not developing breast cancer to age 79 years. CONCLUSIONS: These Australian risk statistics are useful for public information and in the clinical setting. Risks given here apply to women with average breast cancer risk from other risk factors.     

Azoospermia in two brothers with Kartagener syndrome:a family history and diagnosis

0This article describes 2 infertile brothers of asoospermia equally associated with co-existing sinusitis,bronchiectasis,and situs inversus and their family history.These two cases were diagnosed as Kartagener syndrome(KS).The patients were not offspring of kin marriages but their family members with scattered bronchi-pulmouary infections were discovered.No one manifests azoospermia,dextrocardia or situs inversus in the paternal family ex-cept two cases reported.No abnormalities were found in their mother-side family.KS should be differentiated from Young's syndrome,cystic fibrosis(CF),and other diseases such as Kallmann's syndrome in male infertility clinic.     

上皮型钙黏附素基因表达及启动子甲基化与胃癌家族遗传性

目的通过检测家族遗传性胃癌和伴胃癌家族史和肿瘤家族史胃癌及散发性胃癌的E-cd的表达和启动子甲基化情况,探讨E-cd与我国家族遗传性胃癌家系的关系。方法采用免疫组织化学方法检测符合ICG-HGC诊断标准的家族性遗传性胃癌8例和伴胃癌家族史胃癌的30例,伴肿瘤家族史胃癌的30例,散发性胃癌20例的E-cd蛋白表达情况及基因启动子甲基化情况,进行分析,探讨家族性胃癌发生的分τ遗传学基础。结果E-cd在各组胃癌中表达均下调,与正常组织的差异具有统计学意义。家族性遗传性胃癌中E-cd表达下调与其他胃癌组相比差异具有统计学意义。在各组中均不同程度发生E-cd基因启动子甲基化,在家族遗传性胃癌、伴胃癌家族史胃癌与其他组相比差异具有统计学意义。结论E-cd蛋白表达抑制在胃癌中较常见 且在家族遗传性胃癌组降低最明显,同时E-cd基因启动子区甲基化可能是导致E-cd基因表达下调的重要原因 E-cd基因可能是家族遗传性胃癌的分子遗传学基础。     

Factors associated with breast MRI use among women with a family history of breast cancer

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85‐17.06), 2.48 (95% CI, 2.27‐2.71), and 2.50 (95% CI, 2.09‐2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82‐2.75) and OR = 1.76 (95% CI, 1.52‐2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications.