Following the end of the American and Japanese occupation of the Philippines, public health policy continues to be inspired by results of foreign epidemiologic research on suspected pulmonruy carcinogens. Epidemiologic studies on lung cancer conducted in Japan, the United States, and Europe are used to buttress antismcking efforts in developing countries such as the Philippines. Results of retrospective and prospective studies indicate that the majority of those who dieof lung cancer, among American, European, and Japanese women. are cigarette smokers. On the other hand, results of retrospective studies and cancer registries indicate that cigarette smoking is not a significant or essential associated factor in Philippine and other Asian women with lung cancer. Recent efforts by U.S. governmental agencies to regulate environmental tobacco smoke (ETS) in the workplace are being followed in the Philippines. The association between ETS exposure of workers and lung cancer has not been investigated in most developing countries because the conduct of prospective studies is financially burdensome. Occupational. environmental, dietary, and genetic factors are more significant than tobacco use in pulmonary carcinogenesis in Asian women, compared to American black and Caucasian women.

Differences in lung cancer risk between men and women: Examination of the evidence Zang EA, Wynder EL. American Health Foundation, 320 East 433rd Sr., New York, NY 10017. J Nat1 Cancer Inst 1996;88:183-92.

Backgmund: Lung cancer incidence is gradually leveling off in U.S. men but is continuing to rise in U.S. women. This increase in U.S. women exceeds that expected from a slower decline of smoking among women. Recent epidemiologic and biochemical studies suggest gender differences in susceptibility to tobacco carcinogens. Purpose: We conducted an up-to-d$e, more in-depth evaluation of our earlier observation of a potential gender difference in relative risk (RR) of lung cancer due to smoking. We added information from several additional case and control subjects and included more precise histologic classification of the cancer type, accurate quantitation of smoke exposure. and adjustments for body size. Methods: The present investigation was a part of an ongoing hospital-based, case-control study by the American Health Foundation. It included data from 1889 case subjects (I I08 males and 781 females) with lung cancer of squamous/epidermoid, small- cell/oat cell, large-cell, and adenocarcinoma types and 2070 control subjects (II22 males and 948 females) with diseases unrelated to smoking. The case and control subjects were admitted IO participating hospitals from 1981 to 1994and werepair-matchedbyage, sex, hospital, and the time of hospital admission. Ex-smokers and non-Caucasians were excluded from analyses to avoid confounding. The RRs and 95% cotidence intervals were estimated from adjusted odds ratios (0R.s) by use of unconditional multiple logistic regression analysis, and statistical significance was determined by two-sided tests. The ORs for major histologic types were estimated at increasing levels of exposure to cigarette smoke. Resulrs: Our results indicated that women were more likely to be never- smokers than men, particularly those with the squamous/epidermoid-type cancer (8.3% for women versus 2.9% for men 55 years old or older). Men started smoking earlier, reported inhaling more deeply, and smoked more cigarettes per day than women. In contrast, dose-response ORs over cumulative exposure to cigarette smoking were l.2-fold to I .7-fold higher in women than in men for the three major histologic types; these differences were more pronounced for small-cell/oat cell carcinomas and adenocarcinomas than for squamouu’epidermoid carcinomas. Adjustments for weight, height, or body mars index did not alter the ORs. Conclusions: These results confirm our earlier finding that the ORs for major lung cancer types are consistently higher for women than for men at every lwel ofexposure to cigarette smoke. Furthermore, this gender difference cannot be explained by differences in base-line exposure, smoking history, or body size, but it is likely due to the higher susceptibility to tobacco carcinogens in women.

Basic biology

Molecular analysis of a family of cyclin-dependent kinase inhibitor genes @15/MTS2/lNK4b and plUINK4c) in non-small cell lung cancers Kawamata N, Miller CW. Koeffler H?? Cedars-Sinai Medical Instrtute, UCL4 School ofMedicine. 8700 Beverley Blvd, Los Angeles, CA 90048 Mol Carcinog 1995;14:263-8.

Cyclin and cyclin-dependent kinase (CDK) complexes play important roles in modulating the cell cycle. The CDK inhibitors (CDKls) inhibit the kinase activities of these complexes and block the cell cycle. The pl6/multiple tumor suppressor (MT’S) l/inhibitor of CDK4 (INK4) aXDKN2 gene, a CDKI, is frequently deleted in a variety of human cancers. Recently another CDKI gene. plSiMTS2/lNK4b. was cloned and localized to within 20 kb of the pl6 gene. Moreover. a third CDKI gene, named plSANK4b and having a high degree ofprotein homology to ~16, has now been cloned. To elucidate the importance of these CDKI genes in non-small cell lung cancers (NSCLCs), we examined DNAs from 34 NSCLC samples for alterations in these genes by Southern blot and polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP)analyses. Matched control normal tissues from the same individuals were also examined. Homozygous deletions of the ~75 gene were found in three cases. Furthermore, comparativePCR analysis confirmed these deletions and suggested that one additional case had an abnormality of the pl5 gene. Neither rearrangements nor deletions of the pl8 gene were detected By PCR- SSCP and direct sequencing of the aberrantly migrating bands, we detected only polymorphic nucleotide substitutions in both the p75 and pl8 genes. In summary, the frequency of deletions of the ~15 gene was 12% (four of 34 cases), and no point mutations in the ~75 gene were detected in the NSCLCs. For the ~18 gene, no abnormalities were detected. A previous analysis of these NSCLC samples for pl6 gene alterations revealed that the three cases with homozygous deletions of the ~15 gene also have homozygous deletions of the p76 gene.

A study on the levels of calmodulin and DNA in human lung cancer cells Liu G-X, Sheng H-F, Wu S. Department of Resprrototy D~scase, Southwest Hospital, Thn-d Milifav Medrcal Umversily Gaotanyan 630038. Chongqing. Sichuan Province. Br J Cancer 1996;73:899-901.

In order to study the role ofcalmodulin (CaM) in the proliferation of lung cancer cells, the CaM level of the specimens of 40 cases of primary lung cancers and the DNA content of the specimens of 35 cases of primary lung cancers were determined with phosphodiesterase assay and flow cytometry respectively. It was found that the CaM level of lung cancers was significantly higher than that of host lungs, benign lung diseases and normal lungs (P < 0.00 1) and that it was significantly correlated with the histopathological grading and TNM staging of the lung cancers. It was also found that the cellular DNA content of lung cancers, like the CaM level, was also significantly higher than that of benign lung diseases and normal lungs (P < 0.001). There was a significant positive correlation between the cellular DNA content and tissue CaM level in lung cancers (r = 0.885). It is believed that CaM plays an important role in the proliferation of lung cancer cells through the mechanism of the promotion of an uncontrolled synthesis of DNA in the cells. Consequently, it is inferred that CaM antagonists may be tried as a chemotherapeutic agent for lung cancer.

P53 expression, DNA ploidy and S-phase cell fraction in oper- able locally advanced non-small-cell lung cancer Costa A, Silvestrini R, Mochen C. Lequaglie C, Boracchi F’, Faranda A et al.Oncologia Sperimentale C. 1st. Nazionale Studio Cura Tumori. via Venezian 1, 20133 Milan. Br J Cancer 1996;73:914-9.