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11Apr/120

Phytoestrogens and cancer

I recently had to write a short essay for my Cell Biology & Health class, where we could pick any subject as long as it was related to breast cancer. Now, about a year ago I stopped drinking milk (dairy) after hearing some scare stories about growth hormones, and switched to soy milk instead. Then, a few months later, I heard additional scare stories about soy products causing cancer and being worse for you than actual dairy, and abruptly switched back. :P (Though to organic milk from grass-fed cows only.)

So, when this topic came up, I figured it would be a good time to actually check out the link between the phytoestrogens in soy and (breast) cancer for myself. I guess some of you might be interested in reading what I found, so I decided to post my essay here as well.

 

The role of phytoestrogens in the development of breast cancer

Phytoestrogens

Asian countries have a very low incidence of cancer (including breast cancer) compared to Western countries. (1) Is this simply because they have a healthy diet in general – their diet is typically low in fat and red meat, and high in fish – or because they consume a lot of soy products, which are especially rich in phytoestrogens?

Phytoestrogens are plants substances that comprise three main classes: the isoflavones, coumestans and lignans. The isoflavones are structurally similar to endogenous human estrogen, and can bind to the estrogen receptor. (2, 3)

Estrogen and the estrogen receptor (ER)

The estrogen receptors regulate transcription of target genes. Estrogen (or another ligand which is structurally similar) binds to the estrogen receptor; the estrogen-ER complex then binds to estrogen response elements (ERE), regulatory sequences in the target genes. In this way, the binding of estrogen to estrogen receptors stimulates the proliferation of cells in the mammary tissue. This increased proliferation increases the risk of breast tumor development. In addition, the metabolism of estrogen may lead to genotoxic by-products, which will also increase cancer risk. (4)

The effect of phytoestrogens: proposed mechanism of action

Because they are structurally similar to estrogen, isoflavones can bind to the estrogen receptor. They have a lower affinity for the estrogen receptor than endogenous estrogen, but can still compete with it if the phytoestrogens are present in sufficient quantities. Unbound phytoestrogen may be much more abundant in the bloodstream than estrogen, since it has a much lower affinity for binding to serum proteins like albumin. If a lot of phytoestrogen is able to displace estrogen in this way, the effect of estrogen will be much less potent, since phytoestrogen exerts a much weaker effect upon binding to the estrogen receptor. (2, 5)

There are two subtypes of estrogen receptors: ERα and ERβ. The ERβ receptor may have a protective role against breast cancer, by negatively regulating cell proliferation. Each receptor subtype has an affinity for particular ligands, and phytoestrogens show a stronger affinity for the ERβ receptor. (5)

Another way in which phytoestrogens may decrease breast cancer risk is through the estrogen biosynthesis pathway. Some of the key enzymes for estradiol biosynthesis – estradiol being the predominant estrogen in premenopausal women – are aromatase, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase. A bioassay has shown that various isoflavonols and flavonoid structures are aromatase, 3β-hydroxysteroid dehydrogenase and/or 17β-hydroxysteroid dehydrogenase inhibitors, thus decreasing estradiol synthesis. Lower levels of estradiol may also reduce the risk of developing breast cancer. (6)

Evidence supporting the effects of phytoestrogens

Most of the research on the effect of phytoestrogens in humans is observational rather than experimental, which makes it more difficult to establish a causative effect. Experimental studies using soy isoflavones on rodents did not show a significant protective effect against breast tumors. However, if the phytoestrogens were given neonatally or at least pre-puberty, they did have a significant protective effect against the development of breast cancer later in the animals’ life. (1)

In one study, rats were treated with genistein, an isoflavonic phytoestrogen. They developed their mammary glands faster and earlier on than controls, but at a later age their mammary tissue was actually less proliferative. (7) This can be compared to the effect of an early first pregnancy, which is a protective factor against breast cancer. (8) The rats showed increased levels of transforming growth factor alpha (TGF-α) and epidermal growth factor (EGF) at 21 days, but lower levels of TGF-α and EGF at 50 days. These growth factors have a proliferative effect, and upregulated TGF-α and EGF may play a role in the development of cancer. (7)

Most interventions with phytoestrogens or soy products in humans fail to show a protective effect of phytoestrogens against breast cancer. This could be due to the fact that the subjects are almost always adult women who have already gone through puberty. It may be that phytoestrogen intake is only effective at high doses, consumed at young ages (i.e. before the girl reaches puberty). (1, 2) Some studies have shown a decrease in genotoxic metabolites like estradiol, FSH and LH after intervention with soy in women, offering a possible protective effect against breast cancer. (2)

Several epidemiological studies show an association between soy and/or phytoestrogen intake and low breast cancer risk, but generally fail to conclude (with any significance) that phytoestrogens have a protective effect against breast cancer. (2) For instance, some studies on humans show that breast cancer patients have low levels of phytoestrogens, while people with high levels of phytoestrogens are usually in low breast cancer risk groups, but this is not enough information to draw a definitive conclusion on the effect of phytoestrogens. (1) It is also a problem that these studies are observational, so researchers are limited to studying existing populations and their intakes. Among the Asian population phytoestrogen consumption is homogenously high, while it is rather low among the Western population, making it more difficult to establish any significant effect. (2, 3)

Possible adverse effects of phytoestrogens

If a fetus is exposed to high levels of endogenous estrogen prenatally, this increases their risk of developing breast cancer later in life. In rats, a similar effect was observed when administering high levels of phytoestrogen prenatally. However, there has not been any evidence that phytoestrogens have the same effect in humans. (1) Epidemiological studies have not shown any evidence for increased breast cancer risk in populations that consume high levels of phytoestrogens. (2)

Conclusion

There is insufficient evidence to conclude that consumption of phytoestrogens has a protective effect against breast cancer in humans. More experimental research may be necessary to establish a causal association, for instance to test the effect of high phytoestrogen intake in young (pre-puberty) women.

On the other hand, no adverse effects of phytoestrogen consumption on breast cancer development have been reported. Women may safely continue to eat soy products and other foods containing phytoestrogens.

References

  1. H. Adlercreutz: Phytoestrogens and breastcancer. The Journal of Steroid Biochemistry and Molecular Biology, 2002, vol 83(1-5), p 113–118.
    http://www.sciencedirect.com/science/article/pii/S096007600200273X
  2. P.H.M. Peeters, L. Keinan-Boker, Y.T. van der Schouw, and D.E. Grobbee: Phytoestrogens and breast cancer risk. Breast Cancer Research and Treatment, 2003, vol 77, p171–183.
    http://www.springerlink.com/content/g3g4u2j23157n842/
  3. L. Keinan-Boker, Y.T. van Der Schouw, D.E. Grobbee, and P.H.M. Peeters: Dietary phytoestrogens and breast cancer risk. Am J Clin Nutr, 2004, vol 79(2), p282-288.
    http://www.ajcn.org/content/79/2/282.short
  4. B.J. Deroo and K.S. Korach: Estrogen receptors and human disease. J Clin Invest, 2006, vol 116(3), p561–570.
    http://www.jci.org/articles/view/27987
  5. D. M. Harris, E. Besselink, S. M. Henning, V. L. W. Go and D. Heber: Phytoestrogens Induce Differential Estrogen Receptor Alpha- or Beta-Mediated Responses in Transfected Breast Cancer Cells. Exp Biol Med, 2005, vol 230(8), p558-568.
    http://ebm.rsmjournals.com/content/230/8/558.short
  6. J. Le Baila, Y. Champavierb, A. Chuliab, G. Habrioux: Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breastcancer cells. Life Sciences, 2000, vol 66(14), p 1281–1291.
    http://www.sciencedirect.com/science/article/pii/S0024320500004355
  7. N.M. Brown, J. Wang, M.S. Cotroneo, Y. Zhao, and C.A. Lamartiniere: Prepubertal genistein treatment modulates TGF-a, EGF and EGF-receptor mRNAs and proteins in the rat mammary gland. Molecular and Cellular Endocrinology, 1998, vol 144(1-2), p149–165.
    http://www.sciencedirect.com/science/article/pii/S0303720798001063
  8. K. Britt, A. Ashworth and M. Smalley: Pregnancy and the risk of breast cancer. Endocrine-Related Cancer, 2007, vol 14, p907-933.
    http://erc.endocrinology-journals.org/content/14/4/907.full

 

ETA: Wow, the WordPress font and spacing is tiny. This is nearly three pages in my original document... it looks so short here! Haha. Also, if you're a student and you've happened to stumble upon this blog post through a Google search or something, you probably want to look up those sources for yourself, instead of directly quoting another undergraduate's essay which is subject to error. I've even included handy links and everything! ;)

Filed under: Uni, Writings No Comments
20Aug/112

Purple Mountains

This is the first 500-odd words of the 20,000-word fairytale-ish story I wrote for my 2009 Nanowrimo. I dunno why I randomly felt like posting it, but, well, there you go. Unbeta'ed.

 

The gates in front of him were majestic. The knight approached them warily. It had been a long journey; now that he'd come this far, he'd rather not have it come to an abrupt end by being captured at this point. He hopped off his mount and slowly approached the gates on foot. When he felt he was getting close enough to be spotted by the guards, he crouched down low behind a piece of rock that was jutting out from the uneven surface of the ground. His mount tried to make himself invisible behind a large oak tree -- which was not an easy feat, considering it was a twelve foot tall dragon.

The knight reached into his pack and pulled out a specially sharpened piece of glass. He held it up in front of his eyes and studied the large gates from his vantage point. They appeared much closer now. The guards on either side of it were still looking straight ahead, gazing off into the distance. He breathed a sigh of relief. They hadn't been seen.

He rummaged around in his bag again and eventually found a large, mossy green... object. It's purpose became clear when he wrapped it around himself, from his head down to his legs, and suddenly looked rather like a misshapen bush. Curious, the dragon poked out his head from behind the tree to see, sniffing in the knight's direction.

Stay back, he thought, and the beast obliged. He crawled out from behind his rock and over towards the entrance. He went completely still when he felt eyes prickling in his direction and prayed the cheap disguise would work.

The guard on the left side of the gates turned to the one on the right. "Did you just hear... I don't know, some kind of rustling?"

"What, like the wind in the trees? Cause, you know, there's trees all around, and it is pretty stormy," the other replied.

"Yeah, well. This rustling seemed new, somehow. Different. Say, has that bush always been here?"

"You mean the really ugly dark one over there? I'm not sure."

"You'd think we'd remember a bush that pathetic, right?"

Right Guard shrugged. "Guess it could have grown overnight. Groundskeeper said he was going to try some new fertilizer."

"That he got off some wizard, I'm sure, for it to cause that rate of growth." Leftie looked uneasy. "I still say we should investigate it."

"Investigate a bush?! Surely we have better things to do."

There was a moment of uncomfortable silence as they both looked around the outstretched fields in front of them. They were decidedly empty. They usually were. This was only the king's secondary castle, so there wasn't much to do around these parts, most of the time. Suddenly, even investigating a bush seemed like a good way to pass the time.

The chunk of mossy bush decided this conversation had gone on long enough. There was a short swishing sound, and two stones came flying out from between the leaves in rapid succession. A moment later, both guards suddenly dropped to the ground. The knight shook off the assorted gathering of leaves, moss and twigs and turned to the dragon. "You can come out now."

 

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23Jul/111

White Collar fanfic recs & question

So, for the past week, most of my time not spent rewatching WC episodes was spent reading fanfic, instead. I figured it only made sense to link you to some of the stuff I've been reading, so you can all join in on the fun.

I'll start with the first fanfic I started on, after not really reading much of it for any fandom for years. One my Twitter followers whom I knew to be both a Chuck & White Collar fan, posted about having updated her fanfic, so I figured I'd go check it out. Maria (marihun) writes Chuck/WC crossover fanfic; so far, one short story and one ongoing multi-chapter fic. Gen.

Next, through a link that someone shared on Twitter, I discovered daria234's LiveJournal. She's written a ton of WC fanfics, as well as some Chuck, Firefly and a bunch of other fandoms, too. In fact, the list of fics is so long I haven't even finished half of it, but I like most of what I've read so far, so it deserves a rec. Mostly slash, some gen and a tiny bit of het. Warning: includes NC17 fics.

From that LJ, I started following a bunch of links (through comments on the fics etc.) to other journals. Turns out there's a lot of WC fanfiction on LJ -- who knew? TJ, nefhiriel and imbecamiel all have some pretty neat stories, mostly gen. Finally, the most recent LJ that I just started reading yesterday is that of hoosierbitch, which has mostly slash. NC17 warning for this one as well.

(I'm assuming, since you're bothering to read a post about fanfiction, you're familiar with terms like gen/het/slash, NC17 ratings etc? Let me know if I need to explain. :P)

Oh, and remember how I said I would personally never write fanfic ever? Cue not being able to get to sleep a couple nights ago, and finally, at 3.30am or so, grabbing my netbook and, well. Then this happened.

(No, I didn't stay up all the way until 6am. Apparently my Google Docs time zone is rather off. I never noticed this until just now.)

Let us never speak of this again and instead, move on to a question that has been bugging me ever since I initially watched the first two seasons. Warning: I'm about to spoil the entire first two seasons to death. Click the "continue reading" link at your own risk. :P

12Jul/111

Writings

I've been hearing good things about WordPress 3.2. I cannot upgrade to it because, apparently, the server I'm hosted on runs an outdated version of PHP. Maybe it really is time to start looking for a new host.

Anyway. For the past three days, I've been reading crazy amounts of fan fiction (most of it White Collar). I haven't been keeping track, but I wouldn't be surprised if I've literally read about 100,000 words of fic in the past 60 hours. (That's roughly a good-sized novel.)

All this reading is suddenly making me realise just how little writing I've been doing lately. Where by "lately", I mean something like, the last year at least. Okay, sure, just in the last two weeks I've written over 7,000 words' worth of blog posts, and there's also that 10,000-word essay for uni -- which still hasn't been graded and I'm starting to go slightly insane with suspense but that's another story entirely -- but no fiction. Now, I would consider myself more of an artist than a writer, anyway... but I do still love to write. Hell, ever since I discovered the novel concept of comics and being able to get a story out through art, I've doing very few independent sketches, drawings, paintings. (No, this is not a good time to mention RoA has been on hiatus for over half a year. RoA-centric blog post coming up very soon, in fact.)

As I mentioned in one of the recent t-shirt posts, I've done ScriptFrenzy twice, and wrote about 170 pages of screenplay in total. (I just realised I've never bothered to do an exact word count on the RoA script, which is totally not my style. But I would estimate it falls in the 35-40,000 word range.) I've also done NaNoWriMo, what, five times? For those who have no idea what I'm talking about, it's the same concept as Screnzy, except you try to write a 50,000 word novel in a month, rather than a 100 page screenplay. In fact, Screnzy is a Nano spin-off, not the other way around. I've never actually won Nano, admittedly, but with those five attempts combined, I did write about 70,000 words of stories over the years. My best attempt was Nano2009, where I both got my highest word count yet (around 26,000) and, more importantly, actually finished my story. As you might know if you've read the blog post where I squee over winning Screnzy2009, I don't really tend to do that. On the one hand, I insist on writing multi-chapter novel length stories rather than one-shots; on the other, my attention span and inspiration levels are clearly too low to actually finish those, 9 times out of 10.

And it's not like I solely write for challenges like Nano and Screnzy, either. I was penning down stories way before that. I think my first serious attempt at writing a story happened when I was seven-ish. Okay, it probably sucked, I'll be the first person to admit that, but it was a genuine attempt at writing a children's adventure story, instead of just spouting some random illogical little-kid-style drivel. Many more stories followed between that one and my first Nano attempt, some 10 years later.

So then we had that high point in 2009, where I finished both the 170-page RoA screenplay and a 26,000-word fairy-tale-ish story. (That, by the way, I still have only revised the first 40% or so of, so there's no chance of you seeing it any time soon. :P) And then, well, it's almost as if some subconscious part of me thought "better quit while you're ahead", because I've hardly written anything at all, since then.

Okay, I guess I have been busy. From late 2009 to mid-2010, RoA took away a lot of my spare time. It may have been on hiatus for ages at this point, but those first nearly-100 pages didn't exactly draw themselves, you know? Then I started uni, and, not gonna lie, the workload was quite a bit more intense than I'd expected. Okay, I've been getting pretty good marks, and it's not like I've been up all hours of the night studying, every week, to make that happen -- but it's also not as if they just happened, just like that. (I think the biggest problem is -- and I'm trying really hard to come up with a way not to make myself sound like a bragging smart-ass here -- that throughout most of high school and college, a lot of my good marks did kinda "just happen", without huge amounts of studying being involved. So this whole "study hard or you will fail" thing is still a little new to me.)

So, anyway... bottom line is, I haven't written much for the past year and a half or so. I literally haven't written any fiction at all since a tiny 165-word drabble that I did on January 10th at 11.38pm. I know it's this exact date and even time because Google Docs is nice enough to keep track of such things. I know it's 165 words because there's an author's note at the end that says it was written for the "100 word challenge: “Are we there yet?” It’s 165 words. Sue me." (I have no idea where I even got that prompt from, though I'm guessing most likely some Livejournal community. I'm pretty sure I never had any intention to actually post it anywhere, though, much less as a response to said prompt. Also, yes, that means I leave author's notes to myself as if I'm addressing an audience, apparently. I'm only a little bit crazy, I promise.)

I have been feeling like writing, again, lately, but there are a few issues with that. First, okay, it's summer vacation (man, I find a way to rub that under your noses in every damn blog post, don't I) but that doesn't mean I suddenly have a gazillion of free hours. Well, I mean, I kinda do, thanks to not having taking on a summer job and all. But I already want to use those hours for lots of other things, like going on holiday and reworking the RoA script and making awesome drawings and all sorts of fun stuff. Still, that should leave plenty of writing time, I suppose. (Provided I don't do silly things like read some 60 White Collar fan fics in three days. Which I would never. >.>) So secondly, and more importantly, I have no idea what I should write about.

So. How about you throw me some prompts in the comments? I'm not making any promises as to whether that will actually make me write anything, but at least it's a start, right? ;) Preferably ideas that work for original fiction, because for all the reading I do, I've never actually written fanfiction ever. (I'm pointedly ignoring the 500 words or so of Harry Potter fanfiction -- that I wrote when I was like 14 -- into nonexistence. That means the statement still stands.) Though I suppose if you give me a really crazy awesome prompt for some fandom, I could always at least try.

I had a pretty good punchline on which to end this blog, back when I started it some 11 hours ago. Then I had to leave the house before I could finish the last paragraph. Imagine the pretty good punchline going right about here.

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21Jun/091

The Ride

"Five years ago, I stepped onto a train, not knowing where it would take me. It passed through several different places, most of them quite beautiful, others not so great. Now, five years later, I've gotten off that train, at exactly the same stop I got on. Right back where I started? In terms of location -- yes. But as a person? No. That journey has helped me become who I am now; in many ways, I think, a better person than those five years ago. So if I could go back and change it all, would I do so? Again -- the answer is no. It was a wonderful ride, and I wouldn't have missed it for the world. But I'm also glad to be home."

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