Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

Utility of intravoxel incoherent motion diffusion-weighted imaging in predicting early response to concurrent chemoradiotherapy in oesophageal squamous cell carcinoma.

AIM: To investigate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in predicting the early response to concurrent chemoradiotherapy (CRT) in oesophageal squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Thirty-three patients with OSCC who received CRT underwent IVIM-DWI at three time points (before CRT, at the end of radiotherapy 20 Gy, and immediately after CRT). After CRT, the patients were divided into the responders (complete response or partial response) and the non-responders (stable disease) based on RECIST 1.1. The IVIM-DWI parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], the pseudo-diffusion coefficient [D*], and the perfusion fraction [f]) values and their percentage changes (Δvalue) at different time points were compared between the responders and the non-responders. Receiver-operating characteristic (ROC) curve analysis was used to determine the efficacy of IVIM-DWI parameters in identifying the response to CRT. RESULTS: The tumour regression ratio showed negative correlations with ADCpre (r=-0.610, p=0.000), ADC20 Gy (r=-0.518, p=0.002), Dpre (r=-0.584, p=0.000), and D20 Gy (r=-0.454, p=0.008), and positive correlation with ΔD20 Gy (r=0.361, p=0.039) and ΔDpost (r=0.626, p=0.000). Compared to the non-responders, the responders exhibited lower ADCpre, Dpre, ADC20 Gy, and D20 Gy, as well as higher ΔADC20 Gy, ΔD20 Gy, and ΔDpost (all p<0.05). Dpre had the highest sensitivity (92.9%) and value of area under the ROC curve (0.865) in differentiating the responders from the non-responders. CONCLUSION: Diffusion-related IVIM-DWI parameters (ADC and D) are potentially helpful in predicting the early treatment effect of CRT in OSCC.

Development of a rapid mitochondrial DNA extraction method for species identification in milk and milk products.

Isolation of mitochondrial DNA (mtDNA) from milk offers an effective way to monitor aspects of quality control and traceability to ensure food safety. A few methods of DNA isolation from milk have been reported, but many of them are time consuming and expensive. Here, we report a rapid, simple, and efficient method of mtDNA extraction from raw and processed milk (pasteurized, retorted, and UHT milk) to generate substrate for analysis using any PCR analysis platform. Various techniques used for the separation of mitochondria were explored and combined with a sodium dodecyl sulfate method for mtDNA extraction from raw and processed milk. The optimized protocol supports the efficient amplification of mtDNA independent of sample origin and is sufficiently straightforward to allow its widespread adoption by industry.

[A comparative study on treating femal stress urinary incontinence with TVT-Abbrevo and TVT-Obturator].

OBJECTIVE: To compare the effectiveness and complications of TVT-Abbrevo (tension-free vaginal tape-Abbrevo) and TVT-Obturator (tension-free vaginal tape-obturator) for the treatment of female stress urinary incontinence (SUI). METHODS: From Nov.2012 to Nov.2013, 117 patients suffering from SUI were treated with TVT-Abbrebo (n=79) or TVT-Obturator (n=38) procedure, the clinical efficacy and operation-correlated complications were observed. RESULTS: A total of 117 cases, 107 cases of urinary incontinence symptoms disappeared completely, 10 cases were improved. 72 cases (91.1%) were cured and 7 cases (8.9%) were improved in TVT-Abbrevo group; 35 cases (92.1%) were cured and 3 cases (7.9%) were improved in TVT-Obturator group. No significant differences could be found for the curing rates between two groups (P>0.05). Compared with the TVT-Obturator group, the TVT-Abbrevo group had less patients complaining of inner thigh pain at 24 h and 1 w after surgery (P<0.05). No significant differences were observed for the incidence of inner thigh pain at 1m and 1y after surgery between TVT-Abbrevo and TVT-Obturator group (P>0.05). No intraoperative complications such as blood vessel, nerve, bladder damage were recorded and no postoperative retropubic hematoma, tape adjustment and other complications occurred in two goups. No recurrence after 1 year follow-up. CONCLUSIONS: The study shows that TVT-Abbrevo procedure is safe and efficacy in treatment of SUI, and associated with low incidence of recent postoperative inner thigh pain.

Construction of a cDNA library and preliminary analysis of expressed sequence tags in Piper hainanense.

Black pepper is a perennial climbing vine. It is widely cultivated because its berries can be utilized not only as a spice in food but also for medicinal use. This study aimed to construct a standardized, high-quality cDNA library to facilitated identification of new Piper hainanense transcripts. For this, 262 unigenes were used to generate raw reads. The average length of these 262 unigenes was 774.8 bp. Of these, 94 genes (35.9%) were newly identified, according to the NCBI protein database. Thus, identification of new genes may broaden the molecular knowledge of P. hainanense on the basis of Clusters of Orthologous Groups and Gene Ontology categories. In addition, certain basic genes linked to physiological processes, which can contribute to disease resistance and thereby to the breeding of black pepper. A total of 26 unigenes were found to be SSR markers. Dinucleotide SSR was the main repeat motif, accounting for 61.54%, followed by trinucleotide SSR (23.07%). Eight primer pairs successfully amplified DNA fragments and detected significant amounts of polymorphism among twenty-one piper germplasm. These results present a novel sequence information of P. hainanense, which can serve as the foundation for further genetic research on this species.

Analysis of genetic diversity and trait correlations among Korean landrace rice (Oryza sativa L.).

This study analyzed 394 Korean rice landrace accessions, including 93 waxy varieties, for polymorphisms using 29 simple sequence repeat (SSR) markers. In total, 381 alleles served as raw data for estimating the genetic diversity (GD) and population structure. The number of alleles per locus ranged from 3 to 44 (average = 13.14). The expected heterozygosity and polymorphism information content (PIC) ranged from 0.0341 to 0.9358 (mean = 0.5623) and from 0.0783 to 0.9367 (mean = 0.5839), respectively. The mean GDs in waxy, low amylose content, intermediate amylose content, and high amylose content (HAC) varieties were 0.6014, 0.5922, 0.5858, and 0.7232, respectively, whereas the mean PIC values for each SSR locus were 0.5701, 0.5594, 0.5550, and 0.6926, respectively. HAC varieties had the highest GD and PIC. Consistent with clustering by genetic distances, a model-based structural analysis revealed 3 subpopulations. Analysis of molecular variance revealed that the between-population component of genetic variance was 22.35%, and that of the within-population component was 77.65%. Significant correlations were observed between eating quality and protein content (r = -0.262), K(+) (r = -0.655), Mg(2+) (r = -0.680), 1000-GW (r = 0.159), and amylose content (r = -0.134). The overall FST value was 0.2235, indicating moderate differentiation among the groups. Analysis of variance of the 3 genetic groups (mean of 9 phenotypic and 5 physicochemical traits) by the Duncan multiple range test showed significant differences in 10 traits. This preliminary study represents a first step toward more efficient conservation and greater utilization of rice landraces to broaden the genetic bases of commercially grown varieties.

[Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study].

Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P=0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia.

Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML, MIM 601399) is an autosomal dominant disorder characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukaemia (AML). Informative recombination events in 6 FPD/AML pedigrees with evidence of linkage to markers on chromosome 21q identified an 880-kb interval containing the disease gene. Mutational analysis of regional candidate genes showed nonsense mutations or intragenic deletion of one allele of the haematopoietic transcription factor CBFA2 (formerly AML1) that co-segregated with the disease in four FPD/AML pedigrees. We identified heterozygous CBFA2 missense mutations that co-segregated with the disease in the remaining two FPD/AML pedigrees at phylogenetically conserved amino acids R166 and R201, respectively. Analysis of bone marrow or peripheral blood cells from affected FPD/AML individuals showed a decrement in megakaryocyte colony formation, demonstrating that CBFA2 dosage affects megakaryopoiesis. Our findings support a model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to the acquisition of additional mutations that cause leukaemia.

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.

Long noncoding RNA Chaer mediated Polycomb Repressor Complex 2 (PRC2) activity to promote atherosclerosis through mTOR signaling.

OBJECTIVE: Recent studies highlighted long noncoding RNAs (lncRNAs) have been implicated in many biological processes and diseases. However, atherosclerosis is a major risk factor for cardiovascular disease, but the detailed mechanism of atherosclerosis progression remained unclear. In this study, we mainly focused on the role of lncRNA Chaer in atherosclerosis. PATIENTS AND METHODS: RT-PCR was used to detect the expression of lncRNA Chaer in atherosclerosis patients and animal model. Moreover, the expression of Chaer in vascular smooth muscle cell dysfunction model was also measured. Proliferation ability was tested by CCK-8 and cyclin D1 assay, through loss- and gain-of-function approaches. Western-blot was used to measure the expression of H3 lysine 27 methylation, when Chaer was in different levels. RIP and ChIP assay discovered an interaction between Chaer and PRC2 through mTOR signaling. RESULTS: Here we identified a heart-enriched long non-coding RNA, named Cardiac Hypertrophy Associated Epigenetic Regulator (Chaer). We found that the Chaer was highly expressed in serum samples from 28 patients with atherosclerosis, compared with 28 healthy volunteers. Chaer was dramatically upregulated in atherosclerotic plaques of ApoE-/- mice. We also found that the expression of Chaer was upregulated in vascular smooth muscle cell injury model. Through loss- and gain-of-function approaches, we showed that Chaer promotes cell proliferation and induces apoptosis in vitro. Mechanistically, Chaer interacts with Polycomb Repressor Complex 2 (PRC2) through inhibiting histone H3 lysine 27 methylation. Further, this interaction is induced upon mTOR signaling pathway. CONCLUSIONS: According to the results, we found that lncRNA Chaer was closely related to the progression of atherosclerosis, which could be a previously uncharacterized lncRNA-dependent epigenetic checkpoint.

LncRNA TUG1 promotes proliferation of vascular smooth muscle cell and atherosclerosis through regulating miRNA-21/PTEN axis.

OBJECTIVE: Atherosclerosis is a major risk factor for cardiovascular disease, but its mechanism of progression remained unclear. However, many long non-coding RNAs (lncRNAs) have recently been implicated in different processes for cardiovascular disease. In this study, we mainly focused on the role of lncRNA TUG1 in atherosclerosis. PATIENTS AND METHODS: qRT-PCR was used to detect the expression of lncRNA TUG1 in atherosclerosis patients and animal model. Moreover, the expression of TUG1 in vascular smooth muscle cell dysfunction model was also measured. Proliferation ability was tested by CCK-8 and cyclin D1 assay, through loss- and gain-of function approaches. Western-blot was used to measure the expression of PTEN, when TUG1 was in different levels. RESULTS: We found that the lncRNA TUG1 was highly expressed in serum samples from 38 patients with atherosclerosis, compared with 24 healthy volunteers.  LncRNA TUG1 was dramatically upregulated in atherosclerotic plaques of ApoE-/- mice. We also found that the expression of TUG1 was upregulated in vascular smooth muscle cell injury model. Through loss- and gain-of function approaches, we showed that TUG1 promotes cell proliferation and induces apoptosis in vitro. What's more, TUG1 expression level was reversely correlated with PTEN expression in patients with atherosclerosis. LncRNA TUG1 could compete with PTEN for miR-21 binding. CONCLUSIONS: We found that lncRNA TUG1 was closely related to the progression of atherosclerosis, which could be a potential target for treating atherosclerosis.

Single layer centrifugation improves the quality of frozen-thawed sperm of giant panda (Ailuropoda melanoleuca).

The reproductive capacity of captive giant pandas is poor and sperm cryopreservation is necessary for the reproduction and conservation of this species. Cryopreservation, however, leads to a significant decrease in sperm quality, including sperm motility, acrosome integrity and DNA integrity. In the present study, a method was developed based on colloid single layer centrifugation that could significantly improve frozen-thawed sperm quality. Two colloids were compared for post-thaw giant panda sperm preparation; the sperm samples had greater total motility (Colloid 1: 44.5 ±â€¯16.0%, Colloid 2: 42.4 ±â€¯10.1% compared with Control: 25.4 ±â€¯8.4%, P < 0.05), linear velocity (Colloid 1: 17.2 ±â€¯8.3 µm/s; Colloid 2: 19.0 ±â€¯9.0 µm/s compared with Control: 6.6 ±â€¯1.7 µm/s, P < 0.05) and membrane integrity (Colloid: 46.9 ±â€¯13.2%; Colloid 2: 54.3 ±â€¯5.7% compared with Control: 36.0 ±â€¯9.1%; P < 0.05). This method could be a useful tool to enable the use of poor quality sperm samples and benefit this population by using available genetic material.

Germline p53 mutations are frequently detected in young children with rhabdomyosarcoma.

We investigated the possibility that a proportion of children with sporadic rhabdomyosarcoma (RMS) carry constitutional mutations of the p53 tumor suppressor gene. 33 patients with sporadic RMS at two large outpatient pediatric oncology clinics submitted blood samples. Genomic DNA was extracted from peripheral blood leukocytes and PCR was used to amplify exons 2-11 of the p53 gene. Amplified genomic DNA was screened for the presence of germline p53 mutations using single-strand conformation polymorphism (SSCP) analysis. The DNA sequence of those samples that showed aberrant migration of bands on SSCP analysis was determined to identify the precise nature of the gene mutations. Patient records were reviewed to assess clinical correlates of the mutant p53 carrier state. Heterozygous constitutional mutations were detected in 3/33 patient samples screened. Two of these missense mutations are located in exon 7 and one in exon 8 of the p53 gene. The presence of mutations was not correlated with tumor histology, stage, or site. However, an association between young age at diagnosis and presence of a constitutional p53 mutation was noted: 3/13 children under the age of 3 yr at diagnosis carried mutations, whereas none of 20 children over 3 yr of age at diagnosis harbored a detectable constitutional mutation. These results in children with RMS corroborates previous findings in other clinical settings suggesting that the mutant p53 carrier state may predispose individuals to malignancy at an early age. Although this study did not assess whether the mutations were preexisting or new germline alterations, assessment of close relatives of RMS patients for cancer risk and predictive genetic testing may be indicated.

Absence of hereditary p53 mutations in 10 familial leukemia pedigrees.

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms.

Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics.

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, however. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16(INK4a) cell cycle control mechanism in addition to hTERT expression to achieve immortality. To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems. Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16(INK4a)-negative keratinocyte line. In contrast, when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT(+) keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16(INK4a) expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16(INK4a)-dependent mechanism, the activation of which can occur independent of telomere length. Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes without affecting other major growth control or differentiation systems.

Incidence of childhood tumors in Shanghai, 1973-77.

Data of the Shangai Tumor Registry were analyzed for incidence of cancer in children under 15 years of age, 1973-77. The incidence of all malignant neoplasms combined was 104.7 per million boys and 89.2 per million girls. Leukemia, brain tumors, and lymphomas comprised 70% of all childhood tumors in Shangai. Compared with U.S. whites, Shangai children had higher rates of myeloid leukemia and liver cancer and lower rates of lymphoid cancers and tumors of the kidney, eye, soft tissue, and testis. Effects of migration on tumor rates among Chinese children are largely unknown and merit additional study.

Questionnaire study of cancer etiology in 503 children.

Usefulness of an etiologic questionnaire was examined in an interview study of 503 children with cancer. The medical records of the children were abstracted, and their parents responded to a questionnaire-interview to identify genetic and environmental causes of cancer. Among 1,123 siblings of the index patients, 10 developed cancer as compared with 2 expected on the basis of cancer rates for the general population. Cancer risk factors were identified in individual patients with predisposing genetic and congenital disorders: neurofibromatosis (brain tumor), hereditary immunodeficiency (lymphoma), Down's syndrome (leukemia), XY gonadal dysgenesis (germ cell tumor), giant nevus (melanoma), and meningocele (sacral teratocarcinoma). Environmental causes of childhood cancer were difficult to discern because prior exposures were numerous, diverse, and usually ill defined. The questionnaire yielded more data than the medical record on gestational and family history and helped identify patients with exceptionally high cancer risk for additional investigation. Although the findings provide anecdotal confirmation of several associations, few original etiologic hypotheses were generated for formal testing with conventional epidemiologic techniques.

Correlation between cancers of the uterine cervix and penis in China.

A national survey of cancer mortality in the People's Republic of China during 1973--75 revealed concurrent geographic variation for cancers of the uterine cervix and penis, including clustering of both tumors in central parts of the country. The findings are consistent with recent reports from other countries that the cancers tend to aggregate in spouses and with the hypothesis of an etiologic factor in common.

Offspring of patients treated for cancer in childhood.

Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalies or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments.