有肺癌家族史的非小细胞肺癌患者的临床病理特征及预后

目的分析有明确肺癌家族史(FHLC)的非小细胞肺癌(NSCLC)患者的临床病理特征及预后。方法对浦东新区陆家嘴社区卫生服务中心登记的NSCLC切除术后患者的临床病理特征及预后进行分析。结果在428例NSCLC患者中,51例有FHLC。手术患者中早期肺癌的比例在FHLC和非FHLC患者中均较高。FHLC组的肺癌更多的为早期肺癌(P=0.037),且病理类型多为腺癌(P=0.018)。FHLC患者的死亡危险比为0.775(95%CI:0.534-1.275,P=0.327)。结论有FHLC的NSCLC患者具有病理早期和腺癌为主的特点,但其死亡危险比并未减少。     

Familial lung cancer: genetic susceptibility and relationship to chronic obstructive pulmonary disease

Lung cancer continues to be the leading cause of cancer death, and although most lung cancer is attributable to cigarette smoking, underlying genetic susceptibility is suggested by studies demonstrating familial aggregation. The first family linkage study of lung cancer has identified linkage of lung, laryngeal, and pharyngeal cancer in families to a region on chromosome 6q23-25. Because lung cancer and chronic obstructive pulmonary disease (COPD) are known to aggregate in families beyond shared risk associated with smoking, the linkage results are compared and contrasted with results from genomewide linkage and association studies and candidate gene studies searching for genes for lung cancer, lung function, and COPD. Linkage on chromosome 6q to both lung cancer and lung function, and on 12 to lung cancer, COPD, and lung function, together with overlap in candidate genes for these outcomes, suggests that future research into underlying genetic mechanisms of lung disease would benefit from broadening the collection of family history data and better defining the "high risk" population. As familial risk of lung disease is better defined, referral into screening programs and prevention trials can be better targeted to reach families with both a history of lung cancer and COPD.     

Familial aggregation and coaggregation of history of hypertension and stroke

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.     

Familial colorectal cancer

Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH‐associated neoplasia, juvenile polyposis syndrome and Peutz–Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre‐test counselling and appropriate follow up.     

Familial gastric cancer

BACKGROUND: Familial aggregation of gastric cancer has pointed out to a possible hereditary and genetic factor involved in the carcinogenesis of this disease. The diffuse type gastric cancer patients are frequently younger and the tumor has locally infiltrative growth pattern early in its development. Observation of families with frequent early onset gastric cancer has led to the identification of a novel gene implicated in gastric cancer susceptibility: CDH1/E-cadherin. Diffuse familiar gastric cancer is defined as any family presenting: two first-degree relatives with diffuse gastric cancer, one of them with age under 50 years or at least 3 first-degree relatives irrespective age of onset. CASE REPORT: The family reported by us does not fit in any of the classification proposed. The precise identification of these families by clinical and molecular tools is of great importance. The case reported is an example of a family that probably is a form of hereditary gastric cancer not yet fully understood. CONCLUSION: Soon there will be new criteria, possibly including genetic and molecular characteristics.     

Familial pancreatic cancer

Pancreatic cancer (PC) carries a poor prognosis with an overall 5-year survival of less than 10%. Early diagnosis, though cumbersome, is essential to allow complete surgical resection. Therefore, primary and secondary prevention are critical to reduce the incidence and to potentially prevent mortality. Given a relatively low lifetime risk of developing PC, identification of high-risk individuals is crucial to allow identification of pre-malignant lesions and small, localized tumors. Although 85–90% of PC cases are sporadic, we could consider risk stratification for the 5–10% of patients with a family history and the 3–5% of cases due to inherited genetic syndromes. These high-risk populations should be considered for screening and surveillance of PC. MRI/MRCP and EUS are the preferred modalities, due to their high sensitivity in lesion detection. Surveillance should be personalized, considering genetics and family history, and assessment of risk factors that may increase cancer risk. Screening programs should be limited to tertiary referral center, with high-volumes and adequate facilities to manage these patients.     

Familial risk for lung cancer by histology and age of onset: evidence for recessive inheritance

The authors used the Swedish Family-Cancer Database to search for evidence for a genetic predisposition in lung cancer. Familial risks in offspring were increased for all lung cancer to 1.77 when a parent was affected with any lung cancers; the comparable risk among siblings was 2.15. At young age, risks between siblings were higher than those between offspring and parents for all histological types of lung cancer. The present data suggest that 1.7% of lung cancers up to age 68 years are heritable and probably due to a high-penetrant recessive gene or genes that predispose to tobacco carcinogens.     

Familial nommedullary thyroid cancer

Nonmedullary thyroid carcinoma, originating from thyroid epithelial cells, is the most frequent thyroid malignant neoplasia. Since 1955, there has been increasing evidence that this cancer may have a familial predisposition. It is now established that around 4.2% of all nonmedullary thyroid carcinomas occurs on the background of familial predisposition. These cases are often more aggressive, due to early onset, multifocality and a higher percentual of recurrences. An autossomal dominant inheritance pattern appears likely in most families, although the exact genes responsible for this syndrome have not yet been identified. Patients affected by this cancer should be treated with total thyroidectomy routinely and, in most cases, lymph node dissection, followed by iodine ablation and TSH suppressive therapy with levothyroxine. Some authors also recommend that first-degree relatives of patients with nonmedullary thyroid cancer (especially women) should be submitted to neck ultrasound for thyroid cancer screening, aiming early diagnosis for better treatment results.     

Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study

STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to lung cancer, we investigated the association between a family history of lung cancer and subsequent risk of lung cancer in a large-scale, population-based cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791 cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A family history of lung cancer in a first-degree relative was associated with a significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.31 to 2.88). The association was stronger in women than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78, respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI, 1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition, family history was more strongly associated with the risk of squamous cell carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68), while no clear increase in risk was observed in adenocarcinoma and small cell carcinoma. A family history of overall cancer was not associated with an increased risk of lung cancer. CONCLUSIONS: These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves.     

Familial heart block and sinus bradycardia. Classification and natural history

Study of 1 family and review of 18 revealed a spectrum of inherited bradycardia from pure familial heart block (10 families), through combined familial heart block and sinus bradycardia (6 families), to pure familial sinus bradycardia (3 families). Familial heart block occurs in 2 forms, congenital (8 families) and of adult onset (8 families). Either may be associated with sinus bradycardia. Complete heart block appeared to be congenital in all 20 affected members of families with congenital block, resulting in 10 deaths, 8 within the first 10 days of life. A narrow QRS complex did not improve the prognosis of members with complete heart block. Of 17 patients with familial complete heart block of adult onset, 8 died from heart block at a mean age of 47 years. Since partial block preceded complete block in 11 subjects who had prior electrocardiograms, it may be possible to identify family members in whom complete block is likely to develop. In families with pure sinus bradycardia, sinus bradycardia was inherited with a high degree of penetrance. It resulted in nodal rhythm in all 16 affected members and in atrial fibrillation in 9. Atrial fibrillation may be protective in these circumstances, not requiring cardioversion. Sinus bradycardia in families with heart block was usually benign. Various features of formation of the conduction system may provide an embryologie basis for the combined inheritance of sinus nodal disease and heart block. Although the lesions may reside in the sinoatrial node and atrioventricular node-His bundle junction, pathologic correlates of the familial bradycardias require further elucidation.     

Formation of benzo[a]pyrene-DNA adducts in blood monocytes from lung cancer patients with a familial history of lung cancer

Summary The in vitro formation of benzo[a]pyrene-DNA adducts was determined in peripheral blood monocytes of 22 lung cancer patients with at least one first-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/g DNA as compared to 2.1 (0.1) fmol/g in controls (p<0.05), and it was independent of age and smoking habits. These findings support the hypothesis that carcinogen-DNA adduct formation may be one factor of a constitutionally enhanced lung cancer risk.This work was supported by a grant from the German Minister for Research and Technology, BMFT Definition: Pack-year, 1 packet of cigarettes/day x no. years they were smoked     

Familial nonmedullary thyroid cancer.

Familial nonmedullary thyroid cancer (FNMTC) is a syndrome of familial clustering of thyroid cancers of follicular cell origin. It is characterized by multifocality, early onset, more recurrences, and a higher degree of aggressiveness than nonfamilial thyroid cancers of follicular cell origin. An autosomal dominant inheritance pattern with reduced penetrance appears likely in most pedigrees. Although several candidate genes responsible for isolated clinical variants of FNMTC have been identified in single families, the gene(s) responsible for the vast majority of FNMTC cases has yet to be identified. Members of FNMTC cohorts should be followed longitudinally with physical examination and ultrasonography, and aggressively treated when cancer is diagnosed. When cancer is diagnosed, total thyroidectomy should be performed, and most patients should have a prophylactic central neck dissection and a therapeutic lateral functional neck dissection, postoperative radioiodine ablation and thyroid-stimulating hormone (TSH) suppressive therapy. Close follow-up with stimulated thyroglobulin levels, neck ultrasounds, and radioiodine scans are also central to the management strategy.     

Present and past smoking history and other predisposing factors in 100 lung cancer patients.

This study assessed the accuracy of obtaining smoking history, relationships between smoking and the histologic subtypes of lung cancer, past and present smoking history, and co-carcinogen history in 100 patients seen between 1982 and 1989. A standard questionnaire filled out by the patients, a data base filled out by the physician, and medical records were abstracted, and detailed information on smoking and co-carcinogen history was obtained. Eleven percent of the patients were nonsmokers and another 41 percent were former smokers who had quit smoking more than one year prior to the diagnosis of lung cancer. Mean ages at onset and cessation of smoking and diagnosis were 17, 59, and 62 years, respectively. The histologic subtypes were as follows: adenocarcinoma, 34; squamous, 18; small cell, 24; adenosquamous, nine; large cell, nine; and bronchioloalveolar carcinoma, six. Mean pack-years of cigarette smoking for the subtypes were as follows: squamous, 82; small cell, 78; large cell, 72; adenocarcinoma, 65; adenosquamous, 48; and bronchioloalveolar carcinoma, 41. The patient and physician questionnaires had comparable data on smoking status in continued smokers and never smokers. Many former smokers filled out the patient questionnaire as a nonsmoker, but on query by the physician admitted to smoking in the past. The physician data set was more accurate in former smokers than questionnaires completed by the patients. Patients with squamous and small cell carcinomas were heavier smokers than patients with adenosquamous and bronchioloalveolar carcinomas. About 50 percent were active smokers until the diagnosis of lung cancer, but only 18 percent of patients continued to smoke after the diagnosis. About 10 percent were never smokers and about 40 percent were former smokers. Most former smokers quit smoking less than five years antecedent to the diagnosis of lung cancer.