女性肺癌的遗传流行病学研究

通过对１７６个女性肺癌先证者核心家系和１９４个女性对照的核心家系资料分析。发现女性肺癌先证者的一级亲属（父母、同胞）患肺癌的危险性是对照一级亲属（父母、同胞）的１．６７倍，且差异具有显著性。其中女性亲属患肺癌的危险性显著高于对照的女性亲属，ＯＲ值为２．８１（Ｐ＜０．０１）。女性肺癌的遗传度为２０．５４％，遗传因素是女性肺癌的重要危险因素。女性肺癌先证者的女性亲属对肺癌的遗传易感性比男性亲属高。这些结果有助于全面阐明云南省宣威县女性肺癌高发的原因。     

宣威肺癌的遗传流行病学研究

分析了宣威肺癌高发区的３７０对核心家系的资料。结果表明；肺癌的发生具有家族聚集性，肺癌先证者的亲属患肺癌的危险性增加，是配偶家系亲属的１．８５倍。女性亲属是配偶家系女性亲属的２．６４倍。肺癌的遗传属于多基因遗传，其分离比为０．１５，其遗传度为２４．６％，肺癌先证者的亲属对肺癌的易感性比配偶的亲属高。遗传因素是肺癌的危险因素，但不是宣威肺癌高发的主要危险因素。     

肺癌患者亲属对癌症有易感性的研究

分析了３７０例肺癌先证者的核心家系和３７０个对照的核心家系资料，发现肺癌先证者的亲属（父母、同胞）患癌症的危险性明显高于对照的亲属（父母、同胞），前乾是后者的２．０７倍（Ｐ〈０．０１）。其中患癌的危险性是对照亲属的１．８５倍，患其它癌症的危险性是３．７８倍，差别均具有高度显著性统计学意义，表明了宣威肺癌患者的亲属不仅对肺癌的易感性增高，而且对其它癌症的易感性也较高。这些结果都支持了肺癌患者的家系亲属对癌症具有遗传易感性的假设。     

肺癌患者亲属对癌症具有易感性的研究

分析了３７０例肺癌先证者的核心家系和３０个对照的核心家系资料，发现肺癌先证者的亲属（父母，同胞）患癌症的危险性明显高于对照的亲属（父母，同胞）前者是后者的２．０７倍（Ｐ〈０．０１）。其中患肺癌的危险性是亲属的１．８５倍，患其它癌症的危险性是３．７８倍，差别均具有高度显著性统计学意义，表明了宣城威肺癌患者的亲属不仅对肺癌的易感性增高，而且对其它癌症的易感性也较高，这些结果都支持了肺癌患者的家系亲属对     

慢性阻塞性肺部疾病的家族聚集性分析

为了判断慢性阻塞性肺部疾病（ＣＯＰＤ）的家族聚集性，探讨遗传因素对ＣＯＰＤ发病的影响，分析了２０６对核心家系的资料。结果表明：ＣＯＰＤ的发病具有家族聚集性。ＣＯＰＤ先证者的亲属（父母、兄弟姐妹）患ＣＯＰＤ的危险性增加，是对照家系亲属（父母、兄弟姐妹）的２．０７倍。除母亲之外，两家系父亲间，兄弟间及姐妹间患ＣＯＰＤ危险性的差异均具有显著性。故ＣＯＰＤ先证者的亲属对ＣＯＰＤ的易感性比对照的亲属高，说明遗传因素是ＣＯＰＤ的危险因素之一。     

2型糖尿病遗传病因的流行病学研究

对３６３例２型糖尿病先证者家系及２９１例人群对照家系进行了以人群为基础的遗传流行病学病例－对照研究。结果显著的：糖尿病先证者一级亲属（父母、同胞、子女）的累积发病率为３．９４％,对照组一级亲属１．０９％,相对危险度（ＲＲ）为３．６２,差异有非常显著性意义（χ２＝３６．５４,Ｐ＜０．００１）;无论男性或女性一级亲属,先证者组的累积发病率均非常显著地高于人群对照组;诊断时年龄＜５５岁先证者的一级亲属,其糖尿病累积发病率和相对危险度均显著高于诊断年龄＞５５岁组。二项分布显示先证者一级亲属中２型糖尿病的分布呈明显的家庭聚集性,先证者一级亲属的遗传度为４０．４％（男性４２．６％,女性３８．６％）;２型糖尿病在同胞中的分离比为０．０３２,显著低于０．２５,不符合单基因遗传的特征。     

肺癌危险因素的家系分析

通过宣威县３７０对核心家系（肺癌病例的核心家系及对照的核心家系）的分析，表明即使调整了主要环境因素（燃烟煤史及吸烟史）和ＣＯＰＤ史的混杂作用，病例的核心家系亲属（父母、同胞）患肺癌的危险性显著高于对照的核心家系，尤其是女性亲属。说明人群对肺癌的遗传易感性高可能是宣威肺癌高发的重要危害因素。     

16岁以下青少年支气管哮喘的危险因素分析

收集了仅有１６岁以下青少年为子女的支气管哮喘核心家系的资料。２３０个家系资料的分析结果表明：１６岁以下的青少年中，男性患哮喘的危险性是女性的１．６２倍（Ｐ＜０．０１），饮用塘河水的人产生哮喘的危险性明显比饮用自来水的人高（ＯＲ＝１．６７，Ｐ＜０．０５）。父母的哮喘史是青少年最为突出的危险因素，使青少年患哮喘的危险性分别增加２．０６和２．７３倍，且均具有高度显著性意义。此家系分析也显示，母亲的哮喘史对子女产生哮喘的影响更大，约为父亲的两倍。青少年自身的气道高反应性和过敏体质也是青少年产生哮喘的危险因素之一，优势比分别为１．９２和２．０１（Ｐ＜０．０１）。本文揭示了遗传因素在哮喘发病过程中可能的重要作用。     

脑梗塞遗传病因的流行病学系列研究(Ⅰ)

通过遗传流行病学病例对照方法，对宜兴市２１４个家系（１０９个脑梗塞先证家系和１０５个对照家系）进行分离比、多基因遗传方式和遗传度的分析。结果表明：在病例和对照家系具有良好均衡可比性的前提下，脑梗塞的分离比为０．０５２９，显著低于０．２５，说明其不符合单基因遗传病的特征；多基因遗传方式的分析表明，其一级亲属的理论发病率为６．６７８％，与实际发病率８．６１１％相比，无统计学显著性差异，符合多基因遗传的特征；遗传度的估算显示；脑梗塞先证者的一级亲属中，遗传度为５３％，其中女性亲属的遗传度达５７％，显著高于男性亲属的３９．４％，说明在脑梗塞病因中，遗传因素起着一定的作用，特别是对女性作用更明显     

儿童哮喘病遗传流行病学研究

目的　探讨遗传因素在儿童哮喘病发病中的作用。方法　用病例对照的研究方法,确定了１８６ 例哮喘患儿为先证者,收集了１８６ 对核心家系的资料进行了遗传流行病学研究。结果儿童哮喘病具有明显家族聚集性（χ２ ＝ ２４ ．８０ ,Ｐ＜ ０ ．０１） ,先证者Ⅰ、Ⅱ级亲属哮喘病患病率（ 分别为１３ ．６８ ％ 和５ ．３０ ％ ） 明显高于对照组（１ ．９６ ％ ） 。哮喘病分离比为０ ．１４ ,９５ ％ 可信限为０ ．０９７ ～０ ．１８ ,哮喘病Ⅰ、Ⅱ级亲属遗传度分别为７８ ．１８ ％ 和５５ ．０２ ％ ,且女性亲属遗传度（８３ ．６４ ％ ） 明显高于男性（７３ ．４８ ％ ） 。结论　哮喘病属多基因遗传方式,遗传因素是儿童哮喘病的主要危险因素,且对女性更明显     

Familial factors associated with malignant gliomas

Family histories of male patients with histologically confirmed malignant gliomas were compared to family histories of controls (wives). Included were 77 case families with 892 relatives and 77 control families with 719 relatives. Cases had significantly more siblings than controls (P = 0.02), although cases were not preferentially the oldest or the youngest sibs. Odds ratios of two or more were found for mental retardation, Parkinson's disease, and meningitis for the relatives of cases versus controls, but none were statistically significant. The excesses of Parkinson's disease and meningitis were explained by the family of one particularly interesting case containing three relatives with meningitis and two relatives with Parkinson's disease. Noteworthy age-adjusted odds ratios for cancer among relatives of cases compared to relatives of controls were 1.6 (95% confidence interval (CI) = 1.0-2.3) for cancer of any site, 2.4 (95% CI = 0.8-6.1) for breast cancer, and 4.0 (95% CI = 0.6-10.7) for lung cancer. Only the odds ratio for cancer of any site was statistically significant. Overall, 6 of 77 (8%) of cases came from families that included two or more relatives with breast or lung cancer in addition to the proband with malignant glioma. These three cancer sites may form familial clusters worthy of further evaluation in future studies by pedigree and genetic linkage analyses.     

Increased familial risk for non-lung cancer among relatives of lung cancer patients

Reports of two or more anatomically distinct cancer types clustering in families suggest the possible existence of a susceptibility-to-cancer gene. To determine whether a genetic predisposition accounts for such familial aggregation, a retrospective case-control study was conducted in 1976-1979 of 337 southern Louisiana families in each of which a deceased lung cancer patient was used as the proband. A comparison of first-degree relatives of proband families with spouse (control) families revealed a significantly greater overall risk of cancer (odds ratio (OR) = 2.0, p less than 0.0001) in the proband group. Using logistic regression techniques to control for the confounding effects of age, sex, cigarette smoking, and occupational/industrial exposures, relatives of lung cancer probands maintained an increased risk of non-lung cancer (p less than 0.05). The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.16 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.66 and 5.04, respectively. Each risk estimate was significant at the 0.01 level. The most striking differences in cancer prevalence between proband and control families were noted for cancer of the nasal cavity/sinus, mid-ear, and larynx (OR = 4.6); trachea, bronchus and lung (OR = 3.0); skin (OR = 2.8); and uterus, placenta, ovary, and other female organs (OR = 2.1). These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer.     

Aggregation of lung cancer in families: results from a population-based case-control study in Germany

The authors investigated familial aggregation of lung cancer by means of a population-based case-control study, conducted in Germany between 1988 and 1993. They compared lung cancer prevalence in first degree relatives of 945 patients and 983 controls, accounting for various potential risk factors using logistic regression and generalized estimating equations. Some 83% of the study participants were male, and about 14% were below age 51 (young age group). Overall, lung cancer in parents or siblings was associated with a 1.67-fold (95% confidence interval (CI): 1.11, 2.52) increase in lung cancer risk. For the young participants, this risk was 4.75 (95% CI: 1.20, 18.77). Having multiple affected relatives (two or more) was related to a threefold risk elevation (odds ratio (OR) = 2.99, 95% CI: 0.32, 27.55). Paternal (OR = 1.64, 95% CI: 0.91, 2.96) but not maternal (OR = 0.91, 95% CI: 0.32, 2.61) lung cancer was associated with an increased risk of the disease. Lung cancer risk from smoking was particularly pronounced in the parents of cases (OR = 12.20, 95% CI: 3.34, 44.62 vs. OR = 7.93, 95% CI: 2.43, 25.91 in parents of controls). No risk elevation was detected for other smoking-related and other cancers in general. Results confirm previous findings and support the etiologic role of a genetic predisposition to lung cancer.     

Lung cancer risk in families of nonsmoking probands: heterogeneity by age at diagnosis.

In an earlier investigation, we did not detect a major genetic component to lung cancer in families of nonsmoking lung cancer probands. However, heterogeneity with respect to familial aggregation, based on probands' age at diagnosis, was evident. We reanalyzed our previously collected data of 257 families, stratified by age at diagnosis of the probands, using complex segregation analysis. We specifically tested the effects of a Mendelian diallelic gene, history of tobacco use, and history of selected chronic lung diseases in families with a proband diagnosed at the age of 60 years or older and in families with a younger proband (i.e. , under 60 years of age). Cases were identified from the Metropolitan Detroit Cancer Surveillance System. Information on lung cancer occurrence, smoking history, and chronic respiratory diseases in first-degree relatives was obtained for 210 older probands and for 47 younger probands. In older probands' families, no evidence of a major genetic effect was detected. A history of emphysema and tobacco-smoke exposure were found to be significant risk factors. In younger probands' families, a Mendelian codominant model with significant modifying effects of smoking and chronic bronchitis best explained the observed data. Our results suggest the presence of a high-risk gene contributing to early-onset lung cancer in a population where the probands are nonsmokers.     

家族性和散发性鼻咽癌患者的危险因素及肿瘤家族史的比较

目的 研究广东地区家族性鼻咽癌患者与散发性鼻咽癌患者发病因素间存在的差异及其一级亲属恶性肿瘤发病情况,为鼻咽癌患者家庭成员的遗传咨询和筛查策略提供依据.方法 选取2005年10月至2007年10月中山大学肿瘤防治中心收治的广东籍新发鼻咽痛患者作为研究对象,共收集1877例鼻咽痛患者,包括181例家族性鼻咽痛患者和1696例散发病例.对两组患者的人口学特征、临床特征、危险因素及一级亲属肿瘤家族史进行比较分析,并对家族性鼻咽癌患者受累一级亲属的分布及其与先证者发病的时间间隔进行分析.结果 1877例鼻咽癌患者中181例(9.64%)有一级亲属受累;在受累的一级亲属中有58.49%(124/212)为同胞,41.51%(88/212)为父母.同胞与先证者发病的时间间隔为(7.40±5.41)年,而父母与先证者发病的平均时间间隔为(15.55±10.61)年,两者间差异有统计学意义(t=-5.78,P<0.01).两组患者确诊时80%以上临床分期已进入晚期(Ⅲ期以上).无论是患病前还是儿章时期,两组在咸鱼(OR=1.01;95%CI:0.59～1.75 vs OR=1.31;95%CI:0.92～1.86)、腌菜(OR=0.93;95% CI:0.58～1.49 vs OR=1.12;95%CI:0.80～1.57)、酱类(OR=0.37;95%CI:0.14～1.01 vs OR=1.61;95% CI: 0.99～2.48)、新鲜水果(OR=0.87;95%CI: 0.60～1.26 vs OR=0.65;95% CI:0.20～2.12)、腊味(OR=1.26;95%CI:0.87～1.83 vs OR=1.28,95%CI: 0.71～2.30)等饮食因素方面差异均无统计学意义(P值均>0.05).两组患者在吸烟(OR=0.99;95%CI:0.68～1.45)及其一级亲属患其他肿瘤的风险方面(OR=0.85;95%CI:0.56～1.28)差异也无统计学意义(P值均>0.05).结论 在中国广东地区的鼻咽癌患者中,家族性鼻咽癌约占9.64%.在高发家系中,同胞与先证者发病的时间间隔短于父母与先证者发病的时间间隔.大多数患者就诊时已到晚期,建议确诊的鼻咽癌患者的一级亲属,特别是同胞,应根据具体情况定期进行鼻咽癌筛查.     

Familial aggregation of breast cancer with early onset lung cancer.

Site-specific familial aggregation and evidence supporting Mendelian codominant inheritance have been shown in lung cancer. In characterizing lung cancer families, a number of other cancers have been observed. The current study evaluates whether first-degree relatives of early onset lung cancer cases are at increased risk of breast cancer. Families were identified through population-based lung cancer cases and controls under 40 years of age. Cases were ascertained through the Metropolitan Detroit SEER registry; controls through random-digit dialing. Data were available for 384 female relatives of 118 cases and 465 female relatives of 161 controls. Breast cancer in relatives was evaluated after adjusting for age, race, sex, and smoking status of each family member and the sex and age of the probands. A positive family history of early onset lung cancer increased breast cancer risk among first-degree relatives 5. 1-fold (95% CI, 1.7-15.1). Relatives of cases with adenocarcinoma of the lung were at highest risk (RR = 6.3, 95% CI 2.0-20). Mean age of breast cancer diagnosis among relatives of cases was 52.2 years and not statistically different from relatives of controls. Three case families also reported early ovarian cancers (mean age of diagnosis of 35 years). These findings suggest that shared susceptibility genes may act to increase risk of early onset lung and breast cancer in families.     

Effect of cohort differences in smoking prevalence on models of lung cancer susceptibility.

Data on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an individual's pack-years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke--predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected; further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking.     

Validation of family history data in cancer family registries

BACKGROUND: Although family history information on cancer is used to infer risk of the disease in population-based, case-control, cohort, or family-based studies, little information is available on the accuracy of a proband's report. In this study, we sought to determine the validity of the reporting of family history of cancer by probands in population-based and clinic-based family registries of breast, ovarian, and colorectal cancers. METHODS: To assess the accuracy of probands' reported family history of cancer in their relatives, we compared the family history from the personal interview of each proband to a reference standard that included pathology reports, self-reports, or death certificates on the relatives. Our study included 1111 families that accounted for 3222 relatives who were verified. To account for within-family correlations in the responses, we used a generalized estimating equation approach. RESULTS: The probability of agreement between the proband-reported cancer status in a relative with the reference standard varied by cancer site and by degree of relationship to the proband. This probability for first-degree relatives was 95.4% (95% confidence interval [CI]=92.6-98.3) for female breast cancer; 83.3% (95% CI=72.8-93.8) for ovarian cancer; 89.7% (95% CI=85.4-94.0) for colorectal cancer; and 79.3% (95% CI=70.0-88.6) for prostate cancer. CONCLUSIONS: We found high reliability of probands' reporting on most cancer sites when they reported on first-degree relatives and moderate reliability for their reporting on second- and third-degree relatives. Overreporting of cancer was rare (2.4%). Race or ethnicity and gender of the proband did not influence the accuracy of reporting. However, degree of relationship to the proband, type of cancer, age at diagnosis of the proband, and source of ascertainment of probands were statistically significant predictors of accuracy of reporting.