Familial Correlations of the Ages of Manifestation of Lung Cancer and Large-Intestine Cancer

The probability to develop lung cancer before 80 years of age is 1.67 and 0.18% for the male and female populations of Kharkov, respectively; the probability to develop large-intestine cancer is 0.92 and 0.49%, respectively. The correlation coefficient (r) of the age of manifestation (AM) of cancer in parent–offspring pairs is 0.47. These correlation coefficients for the father–son, mother–daughter, mother–son, and father–daughter pairs are 0.64, 0.49, 0.44, and 0.37, respectively. If the parent has lung cancer, the correlation is stronger (r = 0.71). On average, cancer is manifested in offspring earlier than in parents (57 and 63 years, respectively); the differences in the father–daughter and mother–son pairs are 8.2 and 2.8 years, respectively. The best prognostic parameter is the AM of cancer in the father with respect to the AM in the son (b _yx = 0.45).     

Heritability and components of phenotypic expression in skin reflectance of Mestizos from the Peruvian Lowlands

Skin reflectance was measured on the inner upper arm and forehead of a sample of 209 Mestizos ranging in age from 2 to 64 years living in the town of Lamas in the Eastern Peruvian Lowlands. The sample consisted of 43 father-son, 42 father-daughter, 62 mother-son, and 70 mother-daughter pairs. The sample also consisted of 57 brother-brother, 60 sister-sister and 139 brother-sister pairs. The reflectance measurements were made with a Photovolt Reflection Meter, model 670. Stepwise polynomial regression techniques were used to derive standardized residual values. Then using these residual values parent-offspring, sibling intraclass correlations and components of the phenotypic expression of skin reflectance were calculated. The study indicates that 1) the parent-offspring and sibling correlation coefficients conformed with the theoretical correlations expected assuming polygenic inheritance; 2) the husband-wife correlations indicate a high degree of assortative mating for skin color, but despite this effect the parent-offspring and sibling correlation coefficients are lower than the values expected under the influence of autosomal genes; 3) estimates of heritability and components of phenotypic expression indicate that about 55% of the total variability in skin reflectance could be attributed to the influence of additive genetic factors; and 4) there is no evidence of X-linkage in the inheritance of skin color.     

Measurement of Waist and Hip Circumference with a Body Surface Scanner: Feasibility,Validity, Reliability,and Correlations with Markers of the Metabolic Syndrome

Objective

Body surface scanners (BS), which visualize a 3D image of the human body, facilitate the computation of numerous body measures, including height, waist circumference (WC) and hip circumference (HC). However, limited information is available regarding validity and reliability of these automated measurements (AM) and their correlation with parameters of the Metabolic Syndrome (MetS) compared to traditional manual measurements (MM).

Methods

As part of a cross-sectional feasibility study, AM of WC, HC and height were assessed twice in 60 participants using a 3D BS (Vitus^smartXXL). Additionally, MM were taken by trained personnel according to WHO guidelines. Participants underwent an interview, bioelectrical impedance analysis, and blood pressure measurement. Blood samples were taken to determine HbA1c, HDL-cholesterol, triglycerides, and uric acid. Validity was assessed based on the agreement between AM and MM, using Bland-Altman-plots, correlation analysis, and paired t-tests. Reliability was assessed using intraclass correlation coefficients (ICC) based on two repeated AM. Further, we calculated age-adjusted Pearson correlation for AM and MM with fat mass, systolic blood pressure, HbA1c, HDL-cholesterol, triglycerides, and uric acid.

Results

Body measures were higher in AM compared to MM but both measurements were strongly correlated (WC, men, difference = 1.5cm, r = 0.97; women, d = 4.7cm, r = 0.96; HC, men, d = 2.3cm, r = 0.97; women, d = 3.0cm; r = 0.98). Reliability was high for all AM (nearly all ICC>0.98). Correlations of WC, HC, and the waist-to-hip ratio (WHR) with parameters of MetS were similar between AM and MM; for example the correlation of WC assessed by AM with HDL-cholesterol was r = 0.35 in men, and r = -0.48 in women, respectively whereas correlation of WC measured manually with HDL cholesterol was r = -0.41 in men, and r = -0.49 in women, respectively.

Conclusions

Although AM of WC, HC, and WHR are higher when compared to MM based on WHO guidelines, our data indicate good validity, excellent reliability, and similar correlations to parameters of the MetS.     

Dispersal,inbreeding avoidance and reproductive success in white-footed mice

The dispersion pattern of 360 juvenile white-footed mice, Peromyscus leucopus, from 158 matings was monitored to determine whether dispersal was sufficient to prevent close inbreeding. Dispersal was male-biased with 20% of the daughters remaining in their natal home ranges. Dispersal of sons was not ‘forced’ by adult males, but may have been influenced by the presence of their mothers. One mother-son and five father-daughter pairs had overlapping home ranges during the breeding season, but the maximum number of matings among close relatives was three of 135 (2·2%). Dispersal of juvenile males was sufficient to keep close inbreeding at a minimum. Dispersal did not result from reproductive competition. Pregnant and post-lactating females frequently moved to new home ranges. The reproductive success of immigrants was the same as that of natal residents.     

Cancer Incidence among Patients with Anorexia Nervosa from Sweden,Denmark and Finland

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.     

Parent-Child Resemblance in Weight Status and Its Correlates in the United States

Background

Few studies have examined parent-child resemblance in body weight status using nationally representative data for the US.

Design

We analyzed Body Mass Index (BMI), weight status, and related correlates for 4,846 boys, 4,725 girls, and their parents based on US nationally representative data from the 2006 and 2007 Medical Expenditure Panel Survey (MEPS). Pearson partial correlation coefficients, percent agreement, weighted kappa coefficients, and binary and multinomial logistic regression were used to examine parent-child resemblance, adjusted for complex sampling design.

Results

Pearson partial correlation coefficients between parent and child’s BMI measures were 0.15 for father-son pairs, 0.17 for father-daughter pairs, 0.20 for mother-son pairs, and 0.23 for mother-daughter pairs. The weighted kappa coefficients between BMI quintiles of parent and child ranged from −0.02 to 0.25. Odds ratio analyses found children were 2.1 (95% confidence interval (CI): 1.6, 2.8) times more likely to be obese if only their father was obese, 1.9 (95% CI: 1.5, 2.4) times more likely if only their mother was obese, and 3.2 (95% CI: 2.5, 4.2) times more likely if both parents were obese.

Conclusions

Parent-child resemblance in BMI appears weak and may vary across parent-child dyad types in the US population. However, parental obesity status is associated with children’s obesity status. Use of different measures of parent-child resemblance in body weight status can lead to different conclusions.     

Birth in winter can reduce the risk of lung cancer: A retrospective study of the birth season of patients with lung cancer in Beijing area,China

The season of birth is an important risk factor for several diseases. We explored the relationship between birth season and lung cancer. In this population-based retrospective study, we focused on patients with lung cancer who had registered at the Beijing Institute for Cancer Research from 2003 to 2012. In total, 33,025 patients were divided into five subgroups based on their histologic classification, and these five subgroups were compared with the general population (i.e., the permanent resident population of Beijing in 2013). A binary logistic regression method with sex and age as control factors was used to evaluate the relationship between birth season and lung cancer; P < 0.01 was statistically significant. Taking winter as a reference in our analysis of the relationship between season of birth and lung cancer, we found that people who were born in other seasons had a higher probability of developing lung cancer (spring: odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.03–1.09; summer: OR = 1.07, 95% CI = 1.04–1.10; autumn: OR = 1.06, 95% CI = 1.03–1.09) (P < 0.01). Among the five subgroups, persons with squamous cell carcinoma who were born in summer were more likely to develop lung cancer than those who were born in winter (OR = 1.09, 95% CI = 1.02–1.15, P = 0.006). The other subgroups showed no correlation with season of birth (P > 0.01). This study demonstrates that for people born in winter, the risks of developing lung cancer and squamous cell carcinoma are comparatively lower than those for people born in other seasons. Differences in immune function and the maternal nutrition status during pregnancy of people born in different seasons may explain this finding.     

Quantitative genetic analysis of bi-iliac breadth

Bi-iliac breadth, the frontal maximum diameter between right and left iliac crests, was measured in 1,547 male and 2,085 female residents of a rural area in Japan. All subjects were over 14 years of age. The bi-iliac breadth showed an increase related to age but little sex difference. Modification of age and sex variations from the measured value was obtained by calculation of the score, represented by arithmetical means and standard deviations. Distribution of these scores appeared to be binomial, and since binomial distribution approaches normal distribution when n is large, it is presumed that this trait gains normal distribution. Thus variation of bi-iliac breadth in subjects 20-79 years of age enables us to analyze inheritance. No significant difference was found between husband and wife in the correlation coefficients or between father and daughter (0.13 +/- 0.08). Significant differences were found as follows: father-son (0.35 +/- 0.05) (P less than 0.001), mother-son (0.28 +/- 0.05) (P less than 0.001), and mother-daughter (0.28 +/- 0.06) (P less than 0.001). There was no indication of maternal or paternal effects, since no significant difference was found in father-child and mother-child correlation coefficients. It is concluded that bi-iliac breadth is a quantitative genetic trait under control of polygenes on autosomes. Regression coefficient of child on midparental value was 0.55 +/- 0.05, approximately twice the means of four pairs of correlation coefficients between parent-offspring. Narrowly, heritability was estimated as 0.54 approximately 0.55. Contribution of dominance to total variance was small (VD = 0.11), in contrast to the larger additive genetic variance (VA = 0.54).     

Familial aggregation of body mass index: a population-based family study in eastern Finland.

In this study, we investigated the familial aggregation of body mass index (BMI) in a sample of families with young offspring from eastern Finland. 15-year-olds were examined from 1996 to 1997, and their biological parents were examined from 1993 to 1994. 224 children were invited; 184 families participated, and 144 were included in the analysis with complete data. Significant positive correlations were found for mother-offspring pairs (correlation [r] = 0.31, p < 0.001, n = 140), father-offspring (r = 0.23, p = 0.017, n = 107), mother-daughter (r = 0.26, p = 0.044, n = 63) and mother-son (r = 0.36, p = 0.001, n = 77). Adjustment for confounding variables did not alter these results. There was a higher proportion of children in the highest quartile of BMI when the mother was obese (odds ratio [OR] = 3.0, 95 % CI = 1.4 - 6.7, n = 140) and when one or both parents were obese (OR = 2.8, 95 % CI = 1.0 - 8.0 when one parent was obese; OR = 4.6, 95 % CI = 1.1 - 20.0 when both parents were obese; n = 103). The study confirmed familial BMI aggregation. The consistent obesity relationship between mother and offspring may indicate the key role of the mother in primary obesity prevention.     

Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: A correlation with family histories of cancer

Aryl hydrocarbon hydroxylase (AHH) activity was measured in pulmonary alveolar macrophages (PAMs) and peripheral blood lymphocytes from cigarette smokers with and without primary lung cancer. Frequency distribution analysis of AHH induction ratios for the two groups revealed an increased number of individuals in the lung cancer patient group with high lymphocyte induction values (P less than 0.05). A similar increase was not shown for high-PAM AHH values in lung cancer patients (P greater than 0.2). When individual PAM and lymphocyte AHH values were compared between noncancer and lung cancer patients, a positive correlation was observed for noncancer patients (r=0.195, P less than 0.001), but no correlation of these values was noted for lung cancer patients. The lung cancer patients were divided into three subgroups of patients showing (I) high PAM and low lymphocyte AHH levels, (II) low PAM and low lymphocyte AHH levels, and (III) low PAM and high lymphocyte AHH levels. When the incidence of family history of cancer was compared for these subgroups, no family cancer history was recorded for persons in subgroup II; however, individuals in subgroups I and III presented family cancer history incidence of 9.5% and 39.3%, respectively. Patients in group III averaged 6 years younger than those in group I. These data suggest that familial factors may be identified among lung cancer patients and that these factors appear to associate as either a cause of an effect with the capacity of pulmonary alveolar macrophages and lymphocytes to be induced for AHH. The data support the hypothesis that high AHH values may be characteristic of lung cancer patients but show that enzyme values determined from a single tissue, either PAMs or lymphocytes, may not be appropriate for showing whether high AHH inducibility is correlated with lung cancer.     

Increased plasma levels of adrenomedullin, a vasoactive peptide, in patients with end-stage pulmonary disease

AIM: To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases. METHODS: Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study. RESULTS: Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables. CONCLUSIONS: AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.     

Genetic relationships of grizzly bears (Ursus arctos) in the Prudhoe Bay region of Alaska: inference from microsatellite DNA, mitochondrial DNA, and field observations

Grizzly bears are abundant in the region of the Prudhoe Bay oil fields in northern Alaska. We used field observations and molecular genetic data to identify parent-offspring and sibling relationships among bears in this region. We determined genotypes at 14 microsatellite DNA loci and the cytochrome b gene of mitochondrial DNA (mtDNA) for 36 bears. We identified 17 possible mother-offspring pairs and 8 possible father-offspring pairs. This includes verification of the relationships of 14 mother-offspring pairs identified from field observations. Three additional mother-offspring pairs and all eight father-offspring pairs were determined from genetic and age data. Relatedness coefficients based on numbers of shared alleles between individuals were as expected: approximately 0.50 for parent-offspring and sibling pairs and approximately 0.75 for a father-offspring pair resulting from a father-daughter mating. The level of genetic variation (mean number of alleles per locus = 6.6, mean heterozygosity = 70%) and allele frequencies in grizzly bears in the Prudhoe Bay region are similar to those in other parts of the species' range.     

nm23、EGFR和Bcl-2蛋白在肺癌组织中的表达及临床意义

目的:观察nm23、EGFR和Bcl-2在人肺癌中的表达,探讨其与肺癌临床生物学行为的关系。方法:采用免疫组化检测了49例肺癌及癌旁组织中nm23、EGFR和Bcl-2蛋白的表达情况,并对其与肺癌临床生物学行为进行相关分析。结果:在49例肺癌中,EGFR和Bel-2蛋白的阳性表达率分别为51.0%和34.7%,均高于正常肺组织17.5%和12.5%(p<0.05),nm23蛋白的阳性表达率为55.1%,则显著低于正常肺组织87.5%(p<0.01)。在病理分级的高一中分化、低分化和未分化中nm23的阳性表达率分别为82.6%、41.2%和11.1%(p<0.01)。EGFR在非小细胞肺癌(NSCLC)组为61.5%,在小细胞肺癌(SCLC)组为10.0%(p<0.01)。在NSCLC TNM分期中,Ⅰ期 Ⅱ期与Ⅲ P<0.01)期中EGFR的阳性表达率分别为39.3%和81.8%(p<0.01);病理分级的高-中分化和低分化中EGFR的阳性表达率分别为39.1%和88.2%(p<0.01);在淋巴结转移组为57.9%,无淋巴结转移组为27.3%(p<0.05)。Bcl-2的阳性表达率在NSCLC组为25.6%,在SCLC组为70%,统计学分析差异有统计学意义(p<0.01);在NSCLC组病理分级的高分化、中分化和低分化中Bcl-2阳性表达率分别为62.5%、26.7%和5.89%(p<0.01)。结论:癌基因EGFR、凋亡抑制基因Bcl-2与抑癌基因nm23在肺癌的发生、发展中存在着相互促进作用。     

Characteristics of Malignant Tumors in 230 Husband–Wife Pairs

The aim of this study is to obtain a reference point for early detection of tumors in individuals whose spouses were diagnosed with malignant tumors. Data from 230 husband and wife pairs with malignant tumors were collected and analyzed from the family history records of 15,000 people who came to the Department of Cancer Prevention, Cancer Institute/Hospital, Chinese Academy of Medical Sciences for cancer screening between January 2009 and May 2012. The median diagnosis age was 67 years for husbands and 65 years for wives. A total of 214 cases (46.5 %) had digestive system malignancies. Respiratory system cancers were diagnosed in 64 husbands, of whom 20 (31.3 %) had spouses also with respiratory system cancer. Lung cancer ranked first for the females. The total number of lung cancer and commonly seen female-specific cancers (breast, ovarian, uterine, and cervical) was 127 (55.2 %). The difference in age at diagnosis between spouses was less than 10 years in 134 couples (58.3 %), while 77 (33.5 %) couples had an age difference less than 5 years. A family history of malignant tumors in first-degree relatives was documented in 48.3 % of the husbands and 48.7 % of the wives. The occurrence of cancer in both spouses of the couples studied resulted from an interaction between genetic and environmental factors. Nonhereditary factors such as diet, smoking, passive smoking, and air pollution also contributed to the development of cancers. It is recommended that when husband is diagnosed with cancer, the wife should be screened focusing on lung, breast, and gynecological cancers. If the wife was diagnosed with malignant disease, then screening for lung and digestive system cancers should be emphasized in the husband.     

Trends in disability-adjusted life years of lung cancer among women from 2004 to 2030 in Guangzhou,China: A population-based study

BackgroundForecast of disease burden in lung cancer is an important health agenda. One of the main challenges is to predict the evolution of trends in disability-adjusted life year (DALY) of lung cancer so as to anticipate the future burden and to coordinate the supply of sufficient health services and care.MethodsUsing 2004–2013 cancer registry data in Guangzhou, we fitted Bayesian age-period-cohort models with age, period, and cohort effects to analyze trends of lung cancer among women, and then made forecast for DALY of lung cancer until 2030.ResultsDuring 2004–2013, there was an annual average of 10,582 DALYs for lung cancer (15.84% of total DALY). In 2014–2030, DALY is expected to reach 234,752 person-years for lung cancer (12.25% of total DALY), with an annual mean of 13,809 DALYs. Lung cancer crude DALY rate is projected to rise steadily from 257.56 (95% uncertainty interval: 165.97–361.22) in 2014 to 316.99 (219.96–419.41) per 100,000 women in 2030, and the rise is mainly seen in 45–64 years age group. Lung cancer DALY rate remains the highest in the 65–89 years age group.ConclusionsWomen at 65–89 years carry the highest lung cancer burden among other age groups in Guangzhou. The DALY rate of lung cancer is projected to increase most precipitously for the 45–64 years age group. This indicates that concerted efforts are needed to develop adequate cancer services, and to reassess health resources for control and care of lung cancer in these populations.     

Progesterone, 17-OH-progesterone, androstenedione and testosterone plasma levels in spermatic venous blood of normal men and varicocele patients

Progesterone (P), 17-OH-progesterone (17-OH-P), Androstenedione (delta 4) and testosterone (T) plasma levels were measured in spermatic venous blood of twenty-nine varicocele patients (V) and in twelve normal subjects (N). Our data reveal a significant decrease of the mean testosterone in the spermatic blood of varicocele patients with respect to normal controls: (N = 1708.7 +/- 223.8 (SEM) nmol/l, n = 10. V = 1190.9 +/- 101.1 (SEM) nmol/l, n = 29. P less than 0.03). An inverse correlation has been observed between the age of varicocele patients and 17-OH-P (n = 29. y = -33.38x + 1384.70, r = -0.59, P less than 0.01) and delta 4 values (n = 23, y = -1.62x + 85.65, r = -0.49, P less than 0.05). The 17-OH-P/delta 4 ratio appears significantly augmented in varicocele patients with respect to normal controls (n = 4.80 +/- 0.86 (SEM), n = 12. V = 9.65 +/- 1.21 (SEM), n = 23.0.02 greater than P greater than 0.01). This indicates a deficiency in varicocele patients of 17-20 lyase activity. The positive correlation between the P/17-OH-P ratio and age of varicocele patients (n = 28, y = 0.007 x -0.090, r = 0.45, P less than 0.03) suggests a progressive impairment of 17-alpha-hydroxylase in such patients as they grow relatively older. These data demonstrated that the reduced spermatic levels of testosterone in varicoceles are due to the enzymatic impairment of testosterone biosynthesis, concerning firstly 17-20 lyase activity and secondly 17-alpha-hydroxylase activity. The latter enzymatic impairment is age related as is seen from the significant increase of the P/17-OH-P ratio in older patients.     

Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer

Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA-DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04-2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65-9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.     

Cross-cultural correlations of childhood growth and adult breast cancer

International differences in breast cancer incidence and mortality, and studies on Japanese migrants to the United States, point to the importance of environmental factors, including diet and nutrition, in the etiology of breast cancer. Some studies have suggested that dietary patterns in early life are important to the long-term risk of breast cancer. Given that human growth is partially a function of early dietary intake, cross-cultural correlations between breast cancer rates and anthropometric variables measured at different times in childhood provide additional information about the association of early nutrition and cancer. In this study, the associations between food consumption and anthropometric variables, and childhood growth patterns (attained size at age) and adult breast cancer rates, were considered. Data from cross-sectional growth studies conducted during the years 1956-1971 on children aged 6-18 years were obtained for age-specific stature, sitting height, weight, triceps skinfold thickness, arm and chest circumferences, and biacromial and biiliac diameters. National food consumption data were obtained from the United Nations Food and Agriculture Organization (FAO) and socioeconomic status indicators from the United Nations Children's Fund (UNICEF). Cancer incidence data for the years 1972-1977 were obtained from regional cancer registries reported by the International Agency for Research on Cancer (IARC), and mortality data for 1978 were obtained from national cancer registries around the world. Significant correlations were seen between national food consumption data and childhood growth (attained size at age); between cancer incidence and age-specific stature (r = 0.68), weight (r = 0.59), triceps skinfold thickness (r = 0.78), and biacromial width (r = 0.84); and between mortality and age-specific stature (r = 0.77), weight (r = 0.75), and biacromial width (r = 0.78). In general, the correlation coefficients of the observed anthropometric variables with breast cancer increase with increasing age and become highly significant at ages 13-14 years, reflecting cumulative childhood nutritional intake.     

Heritability of bone mass: a longitudinal study in aging male twins

Midshaft radial bone mass was first measured from 1970 through 1972 by photon absorptiometry in 42 pairs of monozygotic (MZ) and 38 pairs of dizygotic (DZ) male Caucasian twins (age 44-55 years). The MZ intraclass correlation (rMZ) of .70 was significantly larger (P less than .05) than the DZ correlation (rDZ) of .45, providing evidence for genetic influences (Smith et al. 1973). Radial bone mass measurements repeated 16 years later (1986-87) on 25 of the MZ pairs and on 21 of the DZ pairs revealed an rMZ of .61 and an rDZ of .44, but the difference was not significant (P greater than .05). The twins had an average radial mass loss of 0.49%/year between the two examinations. The rMZ (.52) and rDZ (.49) values for the 16-year loss in radial mass were both significantly different from zero, but their similar size indicated that the correlations were due to nongenetic factors. In a search for the source of genetic influences on adult radial mass, heritability was estimated by the formula 2(rMZ - rDZ) for radial width and was found to be .66 and .76 (P less than .05) for examinations 1 and 2, respectively. An index of radial density (mass/width) was calculated, and the differences between rMZ and rDZ were not significant at either examination. The intraclass correlations (rMZ = .35; rDZ = .43) were both significant for the loss of bone density between examinations but provided no evidence for genetic influences, results similar to the findings for the loss of mass.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer

Lung cancer is the most common fatal cancer among Danish men, and the incidence rate is increasing among women. In a case-cohort study, we have investigated the occurrence of lung cancer in relation to a high-risk haplotype, previously identified for breast cancer among post-menopausal women, and in relation to the closely linked polymorphisms XPD Asp312Asn and Lys751Gln. Among 54220 members of a Danish prospective cohort study aged 50-64 at entry, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. Among women in the 50-55 year age interval, homozygous carriers of the high-risk haplotype were at increased risk of lung cancer (RR=7.02, 95% CI=1.88-26.18). In the 56-60 year and 61-70 year age intervals, no associations were observed. Among men, no statistically significant associations were found in any age interval. Female homozygous carriers of the variant allele of XPD Lys751Gln were at significantly increased risk of lung cancer in the two younger age-intervals (50-55 years: RR=5.60, 95% CI=1.18-26.45, 56-60 years: RR=10.60, 95% CI=1.50-75.64). Among men, carriers of the variant allele of XPD Lys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval (RR=6.38, 95% CI=0.74-54.90). When the polymorphisms in XPD Asp312Asn and Lys751Gln were mutually adjusted, XPD Asp312Asn was not associated with increased risk of cancer. We found no interaction between genotypes and duration of smoking. In conclusion, two regions of chromosome 19q13.2-3 seem to be associated with risk of lung cancer.