Epidemiology of bronchioloalveolar carcinoma Falk, R T; Pickle, L W; Fontham, E T ...
Cancer epidemiology, biomarkers & prevention,
07/1992, Volume:
1, Issue:
5
Journal Article
Peer reviewed
Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with ...risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.
Previous reports of the association between the debrisoquine polymorphism and lung cancer risk are conflicting. Following the report of an association between lung cancer risk and the variant allele
...CYP2D6(C), we examined the presence of this allele in 98 incident Caucasian lung cancer patients and 110 age, race, and sex matched hospital controls from a case-control study conducted at the National Naval Medical Center in Bethesda, MD. Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8 h urine collected. Genomic DNA was genotyped by a specific polymerase chain reaction amplification and subsequent restrictionenzyme digestion, and Southern analysis. Twenty subjects were heterozygous for the
CYP2D6(C) allele but none were homozygous for this allele. There was no significant difference in frequency of
CYP2D6(C) between lung cancer patients and controls (5.61% and 4.09%, respectively), and there was no significant heterogeneity among cases by histologic type of lung cancer (
P = 0.08). However, 7 of 11 cases (64%) with the
CYP2D6(C) allele had small cell lung cancer, and none had squamous cell carcinoma. Carrying the
CYP2D6(C) allele did not impair debrisoquine metabolism to the same degree as the known inactivating mutations,
CYP2D6(A) and
CYP2D6(B), or deletion of
CYP2D6. Thus, the
CYP2D6(C) allele does not encode a completely inactivating mutation, and the suggestion of a role for this variant allele in the risk for specific histologic types of lung cancer justifies further investigation.
To study the relation of occupational exposures and pancreatic cancer, we evaluated data from males (198 cases and 209 controls) participating in a hospital-based case-control study conducted in a ...high-risk area of Louisiana between 1979 and 1983. The questionnaire obtained information on lifetime occupational history, as well as dietary, smoking, and drinking habits and demographic characteristics. After adjustment for smoking and dietary patterns, white collar occupations showed consistent elevations in risk, whereas associations for other occupations were in general unremarkable. Although not significantly elevated, risks for truck drivers (OR = 1.7) and those with long-term employment in machine repair or as mechanics were suggestive (OR = 2.5). No association was found for jobs in oil refining or oil and gas extraction (ORs were 0.5 and 0.4, respectively), although risks were slightly elevated for long-term workers in the chemical processing industry (OR = 1.2). While these associations deserve further study, our findings are consistent with results of other studies which do not suggest that occupational exposures are important determinants of pancreatic cancer.
Alpha-1-antitrypsin (alpha 1AT) deficiency is a hereditary disorder characterized in adults by a high risk for the development of severe destructive lung disease at an early age. The present study ...was designed to draw conclusions concerning the characteristics of a referral population of 124 patients with alpha 1AT deficiency and symptomatic emphysema. Typically, the alpha 1AT level was 30 mg/dl, and the alpha 1AT phenotype was almost always PiZZ. The individuals in this population were most often male, caucasian, and ex-smokers, and they had become dyspneic between 25 and 40 yr of age. Most routine blood tests were normal. The chest radiographs and ventilation-perfusion studies typically showed abnormalities with a lower zone distribution, and about one third of the study population had evidence suggestive of pulmonary hypertension. Lung function tests were typical for emphysema; the FEV1 and DLCO were the parameters most dramatically reduced, and the annual rate of decline of those parameters was greater than that of the general population. The cumulative probability of survival of this population indicated a significantly shortened lifespan with a mean survival of 16% at 60 yr of age compared with 85% for normal persons.
During meiosis, gene expression is silenced in aberrantly unsynapsed chromatin and in heterogametic sex chromosomes. Initiation of sex chromosome silencing is disrupted in meiocytes with sex ...chromosome-autosome translocations. To determine whether this is due to aberrant synapsis or loss of continuity of sex chromosomes, we engineered Caenorhabditis elegans nematodes with non-translocated, bisected X chromosomes. In early meiocytes of mutant males and hermaphrodites, X segments are enriched with euchromatin assembly markers and active RNA polymerase II staining, indicating active transcription. Analysis of RNA-seq data showed that genes from the X chromosome are upregulated in gonads of mutant worms. Contrary to previous models, which predicted that any unsynapsed chromatin is silenced during meiosis, our data indicate that unsynapsed X segments are transcribed. Therefore, our results suggest that sex chromosome chromatin has a unique character that facilitates its meiotic expression when its continuity is lost, regardless of whether or not it is synapsed.
Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the ...primary data from 20 cohorts.
During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model.
Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status.
Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
Oogenesis is one of the first processes to fail during aging. In women, most oocytes cannot successfully complete meiotic divisions already during the fourth decade of life. Studies of the nematode ...Caenorhabditis elegans have uncovered conserved genetic pathways that control lifespan, but our knowledge regarding reproductive aging in worms and humans is limited. Specifically, little is known about germline internal signals that dictate the oogonial biological clock. Here, we report a thorough characterization of the changes in the worm germline during aging. We found that shortly after ovulation halts, germline proliferation declines, while apoptosis continues, leading to a gradual reduction in germ cell numbers. In late aging stages, we observed that meiotic progression is disturbed and crossover designation and DNA double‐strand break repair decrease. In addition, we detected a decline in the quality of mature oocytes during aging, as reflected by decreasing size and elongation of interhomolog distance, a phenotype also observed in human oocytes. Many of these altered processes were previously attributed to MAPK signaling variations in young worms. In support of this, we observed changes in activation dynamics of MPK‐1 during aging. We therefore tested the hypothesis that MAPK controls oocyte quality in aged worms using both genetic and pharmacological tools. We found that in mutants with high levels of activated MPK‐1, oocyte quality deteriorates more rapidly than in wild‐type worms, whereas reduction of MPK‐1 levels enhances quality. Thus, our data suggest that MAPK signaling controls germline aging and could be used to attenuate the rate of oogenesis quality decline.
In C. elegans germline, aging leads to several changes, including crossover designation, apoptosis, and the quality of the mature oocytes. All of these were previously shown to be controlled by MAPK signaling. We show that arrested oocyte's quality is lower when MAPK is overactivated, yet it can be improved by lowering MAPK via genetic or pharmacological tools.
PDF
