23andme indicates risky genotype for "16q12" region

Hi Tshire:

I wasn't asking you to share the particular SNP (sorry!), but to share it with your counselor. Please also share this information with your current treatment team and any medical oncologist you may consult as well, so they are all fully informed about your risk factors. They may be able to put it into some context for you (for example, tamoxifen is also used as chemoprevention).

I believe one of FDA's concerns in addition to accuracy of testing was that patients are receiving this info and trying to figure it out themselves. I saw a genetic counselor about BRCA testing, consulted with them about the implications of the results (including how they are uninformative is some ways), and also sought advice about what other types of testing to consider. As laypersons, we can read all this (which is good to be informed and shape questions), but we may still not be seeing the whole picture or focusing on the most current and reliable information, the caveats or the clinical implications.

Even though the genetic counselor you consulted uses the Ambry test, since genetic counseling is their field of expertise, they may still be able to advise you about the above results. You could ask them if they are comfortable advising you about this polymorphism, or if not, perhaps they (or your treatment team) can refer you to another genetic counselor with broader practice experience/expertise.

Be sure to ask a counselor about the possibility of an error, and whether any type of confirmatory testing is recommended before you do anything.

I remember the worry I felt while waiting for the BRCA test results (negative). This must be a huge worry added to your burden! Please do seek reliable medical and genetic advice.

Take care,

BarredOwl

Tshire, referring to your original post, I just wanted to point out that tamoxifen does not put women into early menopause. It can alter or stop your periods, but "underneath" your blood hormone levels can be premenopausal. There are injectible drugs (lupron and zoladex) that are used to medically induce menopause so that a woman can use an aromatase inhibitor instead of tamoxifen.

coraleliz and tshire, did you use birth control pills? if so, what is the brand? tshire, how did you find the cancer? you weren't going into get mammos so young, were you? What does 23andme show for your TCF7L2 gene? it's associated with type 2 diabetes as well as breast, colon, and prostate cancer. my mom was an insulin dependent type 2 and died from breast cancer that spread to her bone and brain after years of surviving at stage 4. i was prediabetic and my endocrinologist wasn't concerned, but my ob/gyn put me on metformin 500 mg after i pitched the anti-cancer angle and my family history of breast/colon cancer. i do not have breast cancer or diabetes, but i am higher risk. i am 50.

I was diagnosed at 52. The birth control pill I took for about 2 years was Demulen(It was awful, much worse than Tamoxifen). My GYN at the time was adamant that I take it. He said I had PCOS(polycystic ovarian syndrome). Other GYNs disagreed. But Metformin is sometimes used to treat PCOS.

As for my TCF7L2 gene, I am CC. I am TT for the IGF2BP2 gene. I'll have to review this further.

Hi All:

Interesting discussion.

Tshire: I am inclined to agree with you about your situation. The development of cancer is a multifactorial process, influenced by genes (and there are indeed a variety of genes involved) and by environment - both macro (e.g., environmental exposures, immune surveillance) and micro (the tumor microenvironment). Weila has a family history of colon cancer, so it is difficult to extrapolate from her situation to yours-- other genes or snps may be at play in her family -- known or as yet unknown. The genome is huge.

Also, a predisposition or risk is not predestination. The second page of this Medscape article makes that point for TCF7L2:

http://emedicine.medscape.com/article/1788533-over...

The best part is reproduced below:

• "Although genetic tests for TCF7L2 could help predict the incidence and the rate of onset of type 2 diabetes, the strongest predictors continue to be positive family history, increased body mass index, increased blood pressure, and increased serum levels of triglycerides, apolipoprotein A-1, and liver enzymes, all of which precede inception of metabolic syndrome. In fact, the predictive power of TCF7L2 variants disappears with lifestyle modifications or metformin treatment, while the improved insulin sensitivity resulting from these changes directly oppose the pathological influence of TCF7L2 variants. These data suggest that genetic susceptibility to type 2 diabetes as determined by TCF7L2 variants might prove an actionable indicator for early intervention and disease prevention."

The nice thing is that the lifestyle modifications to reduce breast cancer, and metabolic syndrome and diabetes risk are consistent.

BarredOwl

Weila- As for my PCOS diagnosis. I had some extra hair(abdomen,thighs,face) & was told I had a receding hairline(male pattern baldness-ha!, didn't even realize this until it was pointed out to me). I had 10 periods a year, so a little irregular. My LH was elevated, but that was not really diagnostic because the GYN made no attempt to have it drawn early in my cycle. My prolactin level was also slightly elevated. There was something else that was questionably elevated just don't recall what it was. I also had pretty bad acne but had already cured that with accutane. The GYN made PCOS sound like a terrible disease, I took the birthcontrol pills for almost 2years. He also wanted me to take spironolactone, I refused that one. I've always been thin(actually underweight 5'5' 105lbs).

I have a clean family history as far as cancer, PCOS, diabetes II goes. But I have started to limited my carbs. I started on an anti-inflamation diet & that is part of it. The anti-inflamation diet is helping my achey joints(thank you tamoxifen).

As for 23andme, I have no regrets in paying my $99. Genomics is in it's infancy. I was sad to see the FDA intervene. I think this information belongs in our hands not the physicians. Unfortunately some people "freak out".

Yes, it's true that all we can really do is eat right & exercise. In my case, I was shown to have a 50% risk for macular degeneration. The average risk is 7%. My mom had macular degeneration. I asked the opthamologist about my risk for this with a history in one parent. He said it was elevated but couldn't give me a number but no where near 50%. I told him about my 23andme results. He told me that doctors don't know what to do with those results. He said macular degeneration doesn't come on suddenly & I show no signs of it so far. He also said that all I can really do is eat lot's of green leafy veggies & hope I remain in the 50% without the disease. Since there is treatment(laser) for early stage, i'll definitely keep my yearly eye appts. Let's just say I've been known to procrastinate.

tshire-best of luck with your surgery this week!

"I took the birthcontrol pills for almost 2years.." Coraleliz, what did you do for the PCOS after 2 years? my ob/gyn called me back today. it was the nurse in her office that was handling the PCOS treatment for my daughter. i asked the ob/gyn if she could take over my daughter's treatment and if she had experience prescribing metformin to girls with PCOS. she said yes to both, so i'm making an appt tomorrow. also, there are some supplements now being marketed like ocuvite that came out of studies on macular degeneration. i believe the studies were called the Allred Trials, or something like that.

• my previous ob/gyn suggested i have uterine ablation to take care of my heavy periods. instead i did research and found aleve would cut down on my flow, which it has. i have to live with the results of my healthcare decisions, not my doctors, so i am extremely proactive. for example, a low carb diet might not ultimately stave off diabetes, but the most i have to lose is fat. the benefit outweighs the risk. just as with taking aleve- the risk from it is small, while the risk from a uterine ablation was larger. it's all risk/benefit analysis. testing your blood sugar one and two hours after a bowl of oatmeal and seeing if you go over 140 will not hurt you in anyway. but this is my personality, and the only ones who really have to put up with it are my children and husband. they see the benefits it (being cautious/a researcher/etc) has brought in other areas of our life, so it is easy for them to put up with.

coraleliz, my daughter freaked out when i said i wanted her to try metformin instead of the bc pills. she likes them because she knows when she is going to have her period, and i guess she is fearful of having more hair (she doesn't have that much extra, but she is super muscular) and higher testosterone. i will take to the ob/gyn privately before i do anything with her. the bc pills my daughters are on have the least amount of risk i learned after having to give myself a crash course in different kinds of progestins just so i could make sense of the research paper listed on this site (the paper did not list brands of birth control pills associated with the study for some reason). my 19 year old is on lomedia fe 24, which is low dose estrogen and has one of the safer progestins. my 17 year old is on ortho-tricyclen lo, which is also one of the safer ones. but they still have risks. my older daughter is sexually active, she is just too afraid of getting pregnant, so she wants the double protection of condoms and pills.

i found a study on lean women with PCOS published in 2007: "Role of insulin the in the hyperandrogenemia of lean women with polycycstic ovary syndrome and normal insulin sensitivity"

they gave the women "8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH". i don't know about those drugs. i know that low carb causes less insulin to be secreted and metformin causes greater insulin sensitivity and less insulin to be secreted as metformin reduces glucose production by the liver (gluconeogenesis, i believe).

"Conclusions- In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due it increased sensitivity of their androgenic insulin pathway".

you might try other doctors to get metformin if you still want to try that route. as i said before, low carb is more important for me than metformin in reducing my blood sugar, with exercise second. and sticking to the low carb diet can be difficult. if i am not getting enough sleep and have stress, i will want carbs. so being organized to reduce stress and getting to sleep are the top two priorities on which everything else for my health rests. i am a very disorganized person, so it is a struggle for me.

how did you discover that you had breast cancer? what risk factors do you have?

Pregnancy can also cause breast cancer. Look into Dr Borges studies:

Holysmokes coraleliz! Three years! That is sickening. I learn after dx how worthless mammos are w extremely dense tissue, yet I and I think most women think "I had a clean mammo, I'm good."

the current use of genetic testing is being thwarted across the board. My oncologist said I should not have been given the genetic testing. I learned that Myriad Genetics is refusing to share information. Also what has the FDA done to support collection of genomics in an accessible and legible database not stopping and preventing genomics from being done. At this point, former president Bill Clinton sat on a panel with Craig Ventner and advocated for whole genome testing for us all not just special cases. It looks to me like with the help of the FDA and the NIH women are still dying from breast cancer with no roadmap to a cure. Why are vaccine trials taking so long? The " specialist" cannot even decide on lumpectomy or mastectomy . As a victim of breast cancer I am just not impressed with the confusion and poor management of research from the NIH and NCI.

Of and let us not discuss the $billion given to the start up PCORI to not support any experimental research for patients.

The rudest people I have spoken with are those call backs I received from trials.gov sites. Outrageously poor customer relations. If I even received a call back. Caveat: One site was more responsive: at MD Anderson. But travel costs to Texas are on you

But oh yes let's stop 23and me from providing us with information and allow Myriad to deny access to their databases.

I am hopeful that vaccines from Cuba may become available in the U.S. But big pharmaceutical companies will probably stop them too. Obviously, We need to be protected from our own health information and a real cure.

Why should there still be variants of unknown significance if the data were properly collected and disseminated.

Sorry for my pessimism today was my last day of maximum lifetime dose of radiation a more than 50 year old treatment for breast cancer. New modern?Only issue Marie Curie died from her radiation exposure.