190 Abstracts/Lung Cancer 13 (1995) 185-232

of those 3 1 patients received adjuvant radiotherapy for breast cancer and developed lung cancer a median of 17 years later. Gfthe 19 irradiated patients who subsequently developed lung cancer, 15 did so in the ipsilateral lung and only four had lung cancer contralateral to the previously irradiated site @ < 0.001). Adjwant radiotherapy for breast cancer as delivered decades ago may be an etiologic factor for lung cancer.

Relationship of serum cholesterol, dietary and plasma R-caro- tene with lung cancer in male smokers Scab J, Astre C, Segala C, Gerber M. Groupe Epidemiologie Meta- bolique. INSERM-CRLC, 34094 Montpellier Cedex 5. Eur J Cancer Prev 1995;4:169-74.

It has been hypothesized that D-carotene mediates the association between low serum cholesterol levels and increased risk of lung cancer. It follows from this assumption that this association should be greater in population strata with a low intake of O-carotene than in with those with a high intake. To investigate this hypothesis, we analysed dietary D-carotene, plasma g-carotene and serum cholesterol levels in 20 male smokers with lung cancer and 103 male smoking controls, a subsample taken from a larger case-control study on oxidant-antioxidant status As predicted, we found that the association between low serum cholesterol levels and lung cancer risk was greater in subjects with low plasma D-carotene. Controlling for plasma D-carotene decreased but did not negate the magnitude of the inverse association between serum cholesterol and lung cancer. A low serum cholesterol level tended to increase the risk associated with low plasma D<arotene. Gur data suggest that a low plasma g-carotene does not totally explain the association between serum cholesterol and lung cancer,

High frequency of K-ras mutations in spontaneous and vinyl carbamate-induced lung tumors of relatively resistant B6CFl (C57BL16J I BALB/cJ) mice Massey TE, Devereux TR, Maronpot RR, Foley JF, Anderson MW Environmental Carcinogenesis Program, Nat1 Inst Environm Health Sciences, Research Triangle Park, NC 27709. Carcinogenesis 1995; 16: 1065-g.

The murine K-ras protooncogene is hypothesized to be a pulmonary adenoma susceptibility gene. This postulate is supported by the previous demonstration of a preference for mutation of the K-ras allele from the susceptible parent in lung tumors of A/J x C3H Fl mice. We have examined K-ras activation in control and vinyl carbamate (VC) (single dose 0.03 ImoVg ip.) treated B6CFI mice, the progeny of resistant C57BL/6J and intermediately sensitive BALB/cJ parents. Thirty-four of 37 tumors from VC-treated mice and 17 of 23 from controls contained activating K-ras mutations. The spectra of mutations in codons 12 and 6 1 of K-ras were similar for the two groups, except that 7 tumors from VC-treated mice had A T transversions in the second base of codon 61; none were observed in tumors from saline-treated animals. PCR- based genotyping of first exon K-ras mutations revealed that the vast majority (15 of 18) of the mutations were in the BALB/cJ allele. Furthermore, the three tumors with mutated C57BL/6J K-ras were among the smallest tumors analyzed. These results are consistent with previous findings in other mouse hybrids showing parental bias for K- ras mutations and suggest that mutation of the allele of the susceptible parent may provide a growth advantage to the tumor.

Basic biology

Gender comparisons in human lung cancer: Analysis of ~53 mutations, anti-p53 serum antibodies and C-erbB-2 expression Guinee DG Jr, Travis WD, Trivers GE, De Benedetti VMG, Cawley H, Welsh JA et al. Laboratoty ofHuman Carcinogenesis, National Cancer Institute. National Institutes of Health, Bethesda, MD 20892. Carcinogenesis 1995;16:993-1002.

Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of ~53 mutations, immunohistochemisny, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (4 1%). Sequence analysis of exons 5-8 in 42 females and 49 nudes identified 44 ~53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos, c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for ~53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in tive of nine patients who had serum antibodies recognizing ~53; tumors from these patients were also strongly positive for ~53 by immunohistochemistry These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypotheses regarding gender differences in lung cancer susceptibility.

Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancels from Japanese patients and its association with squamous cell carcinoma Kishimoto Y, Sugio K, Mitsudomi T, Gyama T, Virmani AK, Mclntire DD et al. Department of Pathologv. University of Texas, Southwestern Medical Gene,: 5323 Hany Hines Boulevard Dallas, TX 7S235-8593. J Cancer Res Clin Oncol 1995;121:291-6.

We analyzed 87 Japanese non-smallcell lung carcinomas (NSCLC) including 30 squamous cell, 51 adenocarcinomas and 6 largeceil carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome g, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9Sl26, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%)). Concordance among the four markers was high (87%) indicating that the deletions often were relatively huge. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shirt in band mobility. We noted a high frequency of LOH at 9p especially in squamous cell carcinoma (17 of 29 informative cases or 59%). and iu poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports, we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Gur findings demonstrate that LOH at the short arm of chromosome g is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.