Chromosome instability in lymphocytes from two patients affected by three sequential primary cancers: the role of fragile sites

The chromosomal aberration rate and the expression of fragile sites induced by aphidicolin were evaluated in metaphase chromosomes obtained from peripheral blood lymphocytes of two untreated patients with multiple primary cancers. Spontaneous aberrations of chromosome number and structure and chromosome fragility were compared with controls with the use of the same methods. Chromosomal aberration rates and expression frequencies of fragile sites were significantly higher in the patients than in normal control subjects. In the patients, all but one structural chromosome aberration involved at least one fragile site. Our results suggest that fragile sites may be unstable regions of the human genome, which might play an important role in the genetic instability associated with cancer predisposition.     

Bloom''s syndrome. XIV. The disorder in Japan

Fourteen persons have been diagnosed Bloom's syndrome in Japan, with cytological verification in 11. Widely separated birthplaces throughout Honshu, Shikoku, and Kyushu and a parental consanguinity incidence greater than in the general population suggest that the Bloom's syndrome mutation, although very rare, is distributed widely throughout the Japanese population. The locus mutated is the same as in Jews and persons of Western European extraction. The phenotype differs somewhat from most cases recognized elsewhere, in that dolichocephaly is a less constant feature, the facial skin lesion is less prominent, and life-threatening infections are less common. The characteristic predisposition to neoplasia exists, however, as probably does that to diabetes mellitus.     

The impact of nutrition in urogenital cancers

Prostate, bladder and kidney cancers remain the most common cancers of the urinary tract. Despite improved primary prevention, detection and treatment, the incidence of age-related cancers of the urinary tract is likely to rise as a result of global population ageing. An association of diet with prostate, bladder and kidney carcinogenesis is plausible since the majority of metabolites, including carcinogens, are excreted through the urinary tract. Moreover, large regional differences in incidence rates of urologic tumours exist throughout the world. These rates change when people relocate to different geographic areas, which is suggestive of a strong environmental influence. As a result of these observations, numerous studies have been conducted to assess the effects of diet and nutritional status in kidney, bladder and prostate carcinogenesis. Here, we review the literature assessing the effect of diet and nutritional status on urological cancer risk, which has attracted the most interest.     

Cancer awareness and self-examination practices in young men and women

Participants in this study (N=178) were poorly informed about risk factors, warning signs, and self-examination (SE) practices for two common cancers in young adults, testicular cancer in men and breast cancer in women. Compared to women, men were less likely to know about, see the importance of, or practice SE. We found no relationship between internal locus of control, hypochondriasis, and loneliness, on the one hand, and cancer knowledge and SE, on the other. The best predictors of cancer awareness and SE were fear of developing cancer and self-rated confidence that SE was being done correctly. The results are consistent with a health belief model and self-efficacy theory of health behavior.     

Candidate genes for hereditary colorectal cancer: Mutational screening and systematic review

Genome‐wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM, MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early‐onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population. In the studied cohort, 24 (5%) carriers of (predicted) deleterious variants in the studied genes and no constitutional PTPRJ epimutations were identified. Assessment of allele frequencies in controls compared with familial/early‐onset patients with CRC showed association with increased nonpolyposis CRC risk of disruptive variants in RPS20, IL12RB1, POLE2, MRE11 and POT1, and of FAN1 c.149T>G (p.Met50Arg). Lack of association was demonstrated for LIMK2, PTPN12, LRP6, PTPRJ, POLQ, BLM, MCM9 and FOCAD variants. Additional studies are required to provide conclusive evidence for SEMA4A, WIF1, HNRNPA0 c.?110G>C, and FOCAD large deletions.     

Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority.     

Family attitudes in youth as a possible precursor of cancer among physicians: A search for explanatory mechanisms

A measure of youthful family attitudes, the Closeness to Parents Scale, has continued to be predictive of cancer among physicians in a prospective study of medical students. Nonetheless, questions have remained concerning the meaning and reliability of this measure and whether its predictive value is diminishing over time. Perhaps more important, it is necessary to ascertain whether the relationship is the result of some methodological artifact or whether it is mediated by an association with known risk factors, such as smoking, drinking, and radiation exposure. Each of these issues was examined in turn, using a variety of statistical techniques to refine the scale and to equate cancer and control groups with respect to risk factors as well as possible artifacts. In a group of 913 men, it was found that the scale is primarily a function of good father-son relationships and that its association with later cancer persists even after the influence of possible mediating and artifactual variables is statistically controlled. Several possible explanations for these findings are discussed.This work was supported by National Cancer Institute Grant 1 R18 CA24416-02, National Institute on Aging Grant 1 RO1 GM25822-01, and The Johns Hopkins University.     

良、恶性肝病、卵巢疾病和胰腺疾病患者血清AFP、CEA、CA125和CA199水平的相关研究

目的:血清中AFP、CEA、CA125和CA199的测定研究良、恶性肝病、卵巢疾病和胰腺疾病诊断的临床意义.方法:发光免疫分析测定了52例正常对照组,68例良性肝病,65例肝癌,56例卵巢疾病和51例胰腺疾病的血清中AFP、CEA、CA125和CA199水平,批内CV＜5%,批间CV＜10%.结果:良性疾病患者的血清四项肿瘤标记物水平大致与对照组的相似(p＞0.05).原发性和继发性肝癌患者的血清CA125和CA199水平较对照组显著升高(p＜0.001).卵巢癌与胰腺癌患者也同样如此(0.001＜p＜0.05).结论:血清AFP、CEA、CA125和 CA199的联合测定是诊断和鉴别肝癌、卵巢癌和胰腺癌的最好方法.     

Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

PALB2-mutation carriers not only have an increased risk for breast cancer (BC) but also for pancreatic cancer (PC). Thus far, PALB2 mutations have been mainly found in PC patients from families affected by both PC and BC. As it is well known that the prevalence of gene mutations varies between different populations, we studied the prevalence of PALB2 mutations in a Dutch cohort of non-BRCA1/2 familial PC (FPC) families and in non-BRCA1/2 familial BC (FBC) families with at least one PC case. Mutation analysis included direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and was performed in a total of 64 patients from 56 distinct families (28 FPC families, 28 FBC families). In total, 31 patients (48%) originated from FPC families; 24 were FPC patients (77%), 6 had a personal history of BC (19%) and 1 was a suspected carrier (3.2%). The remaining 33 patients (52%) were all female BC patients of whom 31 (94%) had a family history of PC and 2 (6.1%) had a personal history of PC. In none of these 64 patients a PALB2 mutation was found. Therefore, PALB2 does not have a major causal role in familial clustering of PC and BC in non-BRCA1/2 families in the Dutch population.     

Estrogen and cancers of the colorectum,breast, and lung in postmenopausal women

As estrogens play an important role in maintaining physiological function in various organs, the estrogen decrease after menopause is thought to cause various diseases frequently observed in postmenopausal or elderly women. With the aging of society and a decrease in infectious or vascular diseases, neoplasms have now become the most frequent cause of death in Japan. Cancers of the colorectum, breast, and lung have been rapidly increasing both in incidence and death, especially among postmenopausal women. Interestingly, all three of these cancers are associated with estrogens. In premenopausal women, ovarian estrogens plays major roles in the female reproductive organs through the classic estrogen receptor, ER‐α. In postmenopausal women, however, estrogens produced/activated by peripherally localized estrogen‐metabolizing enzymes such as aromatase, which converts androgen into estrogens, are thought to play physiologically and pathobiologically important roles in various organs through second ER, namely ER‐β, distributing systemically. In this article, the association of estrogens with these cancers in postmenopausal or elderly women are reviewed, especially focusing on the role of ER‐β and peripheral estrogen metabolism. The possibility of prevention or treatment of these diseases through estrogenic control is also discussed.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Natural killing activity is associated with progression of gastric cancer

Previously, we proposed a new analysis of natural killing activity, in which an individual effector/target cell ratio was employed for comparison according to the peripheral number of effector cells. In 51 patients with gastric cancer, the activity was studied using that modified analysis. Natural killing activity was activated in patients with early cancer, where tumor-cell invasion was restricted to the mucosa or the submucosa, even though in well-differentiated adenocarcinoma with invasion of the mucosa alone, the activity remained at the level of controls. In contrast, the activity in advanced cancer, where tumor cells infiltrated beyond the submucosa, came to be inactivated as the cancer progressed. These facts suggest that natural killing activity in patients with gastric cancer is closely associated with tumor invasion and that reactive activation of the activity against tumor is induced, at least, in some patients with early stage.     

A computer model for the study of breast cancer

A computer model was designed as a relational database to assess breast cancer screening in a cohort of women where the growth and development of breast cancer originates with the first malignant cell. The concepts of thresholds for growth, axillary spread, and distant sites are integrated. With tumor diagnosis, staging was performed that includes clinical and sub-clinical states. The model was parameterized to have staging characteristics similar to data published by the Surveillance, Epidemiology, and End-Results (SEER) Program. Validation was accomplished by comparing simulated staging results with non-SEER sources, and simulated survival with independent clinical survival data.     

Cancer survival in Cali,Colombia: A population-based study, 1995-2004

Background:

There is limited information on population-based cancer survival data in Latin America.

Objetive:

To obtain estimates of survival for some cancers recognized as a public health priority in Colombia using data from the Cancer Registry of Cali for 1995-2004.

Methods:

All cancer cases for residents of Cali were included for the following sites: breast (3,984), cervix uteri (2,469), prostate (3,999), stomach (3,442) and lung (2,170). Five-year relative survival estimates were calculated using the approach described by Estève.

Results:

Five-year relative survival was 79% in patients with prostate cancer and 68% and 60% in women with breast or cervix uteri cancer, respectively. The cure fraction was close to zero in subjects with lung cancer and less than 10% in those with stomach cancer. The probability of dying from breast or prostate cancer in people in the lower socio-economic strata (SES) was 1.8 and 2.6 times, respectively, when compared to upper SES, p <0.001. Excess mortality associated with cancer was independent of age in prostate or breast cancer. After adjusting for age, sex and SES, the risk of dying from breast, cervix uteri, prostate and lung cancer during the 2000-2004 period decreased 19%, 13%, 48% and 16%, respectively, when compared with the period of 1995-1999. There was no change in the prognosis for patients with stomach cancer.

Conclusions:

Survival for some kinds of cancer improved through the 1995-2004 period, however health care programs for cancer patients in Cali are inequitable. People from lower SES are the most vulnerable and the least likely to survive.     

The risk of contralateral breast cancer in daughters of women with and without breast cancer

We aimed to estimate the 15‐year and lifetime risks of contralateral breast cancer in breast cancer patients according to the age of diagnosis of the first cancer and the history of breast cancer in the mother. The risks of contralateral breast cancer were estimated for all 78,775 breast cancer patients in the Swedish Family‐Cancer Database (age at diagnosis of first breast cancer <70 years). The risk of experiencing a contralateral breast cancer within 15 years of diagnosis was 8.4% [95% confidence interval (CI): 8.1–8.7%] for women with an unaffected mother, was 12% (95%CI: 11–13%) for a woman with a mother with unilateral breast cancer and was 13% (95%CI: 9.5–17%) for women with a mother with bilateral breast cancer. In early‐onset diagnosed women (<50 years) with an unaffected mother, the risk of contralateral breast cancer until age 80 was 23% (95%CI: 20–26%) and for late‐onset (50–69 years) diagnosed women it was 17% (95%CI: 14–21%). In a woman with a mother with an early‐onset unilateral breast cancer, risk of contralateral breast cancer by age 80 was 35% (95%CI: 25–46%). Women with a mother with early‐onset bilateral breast cancer had 31% (95%CI: 12–67%) lifetime risk of contralateral breast cancer. The risk of contralateral breast cancer is higher for daughters of breast cancer patients than for daughters of women without breast cancer. Maternal cancer history and age at onset of first breast cancer in women should be taken into account when counseling breast cancer patients about their risk of contralateral breast cancer.     

Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients

There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, and whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for the implementation of RAD51C into routine clinical genetic testing. Consequently, we have performed a large RAD51C mutation screen of hereditary breast and ovarian cancer families, and the first study of unselected patients diagnosed with ovarian cancer. Our data confirm a consistent but low frequency (2/335 families) of inactivating RAD51C mutations among families with a history of both breast and ovarian cancer and an absence of mutations among breast cancer only families (0/1,053 families). Our data also provide support for the designation of the missense variant p.Gly264Ser as a moderate penetrance allele.