more info about women and lc

[john]

Project 2

Role of Estrogen in the Development of Lung Cancer

Principal Investigator(s): Chhanda Gupta, Ph.D.

Co-Investigator(s): Jill M. Siegfried, Ph.D.; James D. Luketich, M.D.; Harry S. Wieand, Ph.D.

Increasing evidence is emerging that women are more susceptible to lung cancer than men, suggesting a role for estrogen in the development of this disease. Estrogens are known to act as tumor promoters through a receptor-mediated mechanism in reproductive organs. These are some reports of estrogen receptor expression in lung tumors, and it is possible that the lung is an estrogen-responsive organ. Recent findings that early menopause is associated with a reduced lung cancer risk and that use of estrogen replacement therapy results in an increased incidence of lung cancer supports this speculation. Additional support for this hypothesis comes from our recent studies, which identified much higher expression of both estrogen receptor (ER) a, and in some cases ERb, in non-small cell lung tumor cells than in normal bronchial epithelial cells or fibroblasts from the lung. Estrogen induced increased cell growth in lung tumor cell lines in vitro and this effect was blocked by the anti-estrogen ICI 182,780. Estrogen also enhanced growth of the lung tumor cell line H23 in immunocompromised mice. Tamoxifen, an inhibitor of estrogen, reduced the in vivo growth of the lung tumor by itself, but enhanced it in the presence of estrogen, suggesting tamoxifen may be a partial agonist in the lung, as it is in the uterus and bone. Based on these findings, we hypothesize that estrogen plays a direct role in promoting lung cancer through a receptor-mediated mechanism and may be responsible for at least some of the increased risk of women to lung cancer. Estrogenic effects may also help explain the high proportion of women among non-smokers who are diagnosed with lung cancer. Project One of this SPORE application found that expression of the Gastrin-Releasing Peptide Receptor (GRPR) gene was associated with a diagnosis of lung cancer in non-smoking women, and that GRPR expression was enhanced by estrogen in lung cells expressing the ERb. This suggests a mechanistic link between estrogen and lung cancer risk. In Project Two of the SPORE, we will examine the role of estrogen in more depth. The Specific Aims are: (1) Determine the frequency and level of expression of the ERa and ERb in lung tumors and normal lung tissues; (2) examine ability of estrogens to enhance tumor cell proliferation in vitro and in vivo, and ability of anti-estrogens to oppose this effect; (3) determine relative mRNA expression levels of the ERs in biopsies of the human airway of normal and preneoplastic histology from current and former smokers; (4) determine effect of estrogen on expression of three genes important in lung cancer proliferation; and (5) examine in on-going clinical trials, and in female subjects from Project One, whether estrogens influence lung cancer risk

[SandyS]

Estrogenic effects may also help explain the high proportion of women among non-smokers who are diagnosed with lung cancer.

Gee - you think a comment like that would get Revlon to admit that Lung Cancer IS a women's cancer?

SandyS

[pecola]

Hi-Five, Sandy! Good point.

Thanks for always providing such fantastic information, John. This is an exciting study.

Gina

[chloesmom]

Here's something interesting about my particular situation. Highly estrogen receptive breast tumor. Tamoxifen--2 years later, lung tumor. Thankfully, I am now menopausal, which, according to this study, or at least, their theory, is a good thing. Now my question is, should I continue on with the tamoxifen, or switch to arimidex in november, which is the current plan?

[Debi]

I have to admit that everytime I read something about estrogen causing lung cancer, I take a breath..

I had had some "woman" problems over 10 years ago and my doctor did quite a few tests. The end results were that I was having so many problems because my body manufactured way too much estrogen. At the time, I was told the only solution would have been to take birth contol pills which wasn't an option because I was just over 35 and I smoked. So basically, I learned to live with my problem and extra estrogen supply.

I have never commented before on the estrogen posts because it is like that dark corner that I don't want to go into because I am afraid of what I'll find..yes, I know that smoking contributed at least in part to my getting lung cancer, but how much responsibility did my own body have? Its somehow easier for me to just blame it on smoking than to think my own built in chemical lab has a shorted fuse somewhere. Not sure if that makes sense to anyone other than me .....

[chloesmom]

Debi,

Makes perfect sense to me--yes, of course smoking didn't help with the whole thing, but an adeno type tumor is glandular, and that kind of thing can be hormonally fed, just like my breast tumor was.

My gynocologist told me that these kind of glandular things follow each other sometimes, and to absolutely not let my 50th year come and go without a colonoscopy--don't worry, I won't.

In my case, I blame smoking, radiation, and estrogen for my lung tumor. The good news is all three of those items are pretty much out of my life now.

I don't know, it makes sense to me...

[Donna G]

I just heard on the weather channel that 85% of lightning to people strikes are to men. Does that even us out any? Donna G

[Connie B]

I should say Donna G. GOOD ONE!!!!