Cancer & risk factors by Mayo Clinic

Hindsfeet · January 2010

Cancer Cancer - Comprehensive overview covers cancer symptoms, causes and treatments. Definition

Cancer refers to any one of a large number of diseases characterized by the development of abnormal cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissue. Cancer also has the ability to spread throughout your body.

Symptoms

Signs and symptoms caused by cancer will vary depending on what part of the body is affected. Some general signs and symptoms associated with, but not specific to, cancer include:

Fatigue
Fever
Lump or thickening that can be felt under the skin
Pain
Weight changes, including unintended loss or gain
Skin changes, such as yellowing, darkening or redness of the skin, sores that won't heal, or changes to existing moles
Changes in bowel or bladder habits
Persistent cough
Difficulty swallowing
Hoarseness
Persistent indigestion or discomfort after eating

Causes

Cancer is caused by damage (mutations) to the DNA within cells. Your DNA contains a set of instructions for your cells, telling them how to grow and divide. Normal cells often develop mutations in their DNA, but they have the ability to repair most of these mutations. Or, if they can't make the repairs, the cells often die. However, certain mutations aren't repaired, causing the cells to grow and become cancerous. Mutations also cause cancer cells to live beyond their normal cell life span. This causes the cancerous cells to accumulate.

In some cancers, accumulating cells form a tumor. But not all cancers form tumors. For example, leukemia is a cancer that involves blood, bone marrow, the lymphatic system and the spleen, but doesn't form a single mass or tumor.

The initial genetic mutation is just the beginning of the process by which cancer develops. Scientists believe you need a number of changes within a cell in order to develop cancer, including:

An initiator to cause a genetic mutation. Sometimes you're born with this genetic mutation. Other times a genetic mutation is caused by forces within your body, such as hormones, viruses and chronic inflammation. Genetic mutations can also be caused by forces outside of your body, such as ultraviolet (UV) light from the sun or cancer-causing chemicals (carcinogens) in your environment.
A promoter to cause rapid cell growth. Promoters take advantage of genetic mutations created by initiators. Promoters cause cells to divide more rapidly. This could lead to an accumulation of cells, such as a tumor. Promoters could be inherited, could come from inside your body or could come from outside your body.
A progressor to cause cancer to become aggressive and spread. Without a progressor a tumor may remain benign and localized. Progressors make cancers more aggressive, more likely to invade and destroy nearby tissue, and more likely to spread to other parts of your body. Like initiators and promoters, progressors could be inherited or they could come from environmental sources.

Your genetic makeup, forces within your body, your lifestyle choices and your environment can all set the stage for cancer or help complete the process once it's started. For instance, if you've inherited a genetic mutation that predisposes you to cancer, you may be more likely than other people to develop cancer when exposed to a certain cancer-causing substance. The genetic mutation begins the cancer process, and the cancer-causing substance could play a role in further cancer development. Likewise, smokers who work with asbestos are more likely to develop lung cancer than are smokers who don't work with asbestos. That's because tobacco smoke and asbestos both play roles in cancer development.

Risk factors

While doctors have an idea of what can put you at risk of cancer, the majority of cancers occur in people who don't have any known risk factors. Factors known to increase your risk of cancer include:

Your age
Cancer can take decades to develop. That's why most people diagnosed with cancer are 55 or older. By the time a cancerous mass is detected, it's likely that 100 million to 1 billion cancer cells are present, and the original cancer may have been growing for five years or more. While it's more common in older adults, cancer isn't exclusively an adult disease - cancer can be diagnosed at any age.

Your habits
Certain lifestyle choices are known to increase your risk of cancer. Smoking, drinking more than one drink a day (for women) or two drinks a day (for men), excessive exposure to the sun or frequent blistering sunburns, and having unsafe sex can contribute to cancer. You can break these habits to lower your risk of cancer - though some habits are easier to break than others.

Your family history
Only about 10 percent of cancers are due to an inherited condition. If cancer is common in your family, it's possible that mutations are being passed from one generation to the next. You might be a candidate for genetic screening to see whether you have inherited mutations that might increase your risk of cancer. Keep in mind that having an inherited genetic mutation doesn't necessarily mean you'll get cancer.

Your health conditions
Some chronic health conditions, such as ulcerative colitis, can markedly increase your risk of developing certain cancers. Talk to your doctor about your risk.

Your environment
The environment around you may contain harmful chemicals that can increase your risk of cancer. Even if you don't smoke, you might inhale secondhand smoke if you go places where people are smoking or you live with someone who smokes. Chemicals in your home or work place, such as asbestos and benzene, also are associated with an increased risk of cancer.

CameoBarbie · January 2010

I am wondering about high risk assessement. I was surfing, and so, have a serious question for anyone who might know. The "p16 and p53 tumor suppressors that are somewhere with BRCA2" are also found to be a factor in pancreatic cancer. My father died of pancreatic cancer. All the women on my Mother's side are clear. My father died quite young at 54 within 21/2 years of diagnosis of his illness.

Is it proper to write a letter to the Physician who 'treated' him to have them consider whether I am just too 'out there' with this thought? Would involving them in this at all be like applying for the presidency with just a mop?

I wonder if they would even have his records available still from 1997.

I really thought I was satisfied with fibrocystic change but ... Any answer would be very appreciated. Thank you.

LISAMG · January 2010

Dear Cameo,

There is a direct correlation between hereditary pancreatic cancer and the BRCA2 gene, especially since your father died young. Any BC, OVCA or Melanoma at all on your Dad's side? Have you had and/or considered genetic counseling/testing??

leaf · January 2010

A genetics counselor is the expert. But just because you have a first degree relative with pancreatic cancer does NOT mean you have a BRCA change.

They don't even mention pancreatic cancer in the guidelines below. It is certainly POSSIBLE to have only pancreatic cancer in one's family and have a known BRCA 1/2 mutation; it is just not highly likely. In the statement below, it says that (barring family patterns such as no daughters in a family, few members in a generation, adoption, uncertainty in diagnosis, etc.) Women who have none of these family history patterns have a low probability of having a harmfulBRCA1 or BRCA2 mutation.

These are the guidelines on who should get genetically tested, according to the USPTF.

For women who are not of Ashkenazi Jewish descent:two first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was diagnosed at age 50 or younger;three or more first-degree or second-degree (grandmother or aunt) relatives diagnosed with breast cancer regardless of their age at diagnosis;a combination of first- and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person);a first-degree relative with cancer diagnosed in both breasts (bilateral breast cancer);a combination of two or more first- or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis;a first- or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis; andbreast cancer diagnosed in a male relative. For women of Ashkenazi Jewish descent:any first-degree relative diagnosed with breast or ovarian cancer; andtwo second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer.The likelihood of a harmful mutation in BRCA1 or BRCA2 is increased with certain familial patterns of cancer. These patterns include the following (15):These family history patterns apply to about 2 percent of adult women in the general population. Women who have none of these family history patterns have a low probability of having a harmfulBRCA1 or BRCA2 mutation.

http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA

Estimated new cases and deaths from pancreatic cancer in the United States in 2009:
New cases: 42,47 Deaths: 35,240

http://www.cancer.gov/cancertopics/types/pancreatic

No direct measures of the prevalence of clinically important BRCA1 or BRCA2 mutations in the general, non-Jewish U.S. population have been published; however, models have estimated it to be about 1 in 300 to 500.^13-16 Prevalence estimates in a large study of individuals from referral populations with various levels of family history ranged from 3.9 percent (no breast cancer diagnosed in relatives <50 years of age and no ovarian cancer) to 16.4 percent (breast cancer diagnosed in a relative <50 years of age and ovarian cancer diagnosed at any age).¹⁷ http://www.ahrq.gov/clinic/uspstf05/brcagen/brcagenrs.htm#discussion

In this study of Ashkenazi Jews, about 3/4 of the pancreatic cancers were thought NOT to be due to a known BRCA 1/2 mutation.

In summary, from among 23 families with pancreatic cancer, 6 (26%) informative BRCA1/2 mutation carriers were identified, equally cosegregating the 185delAG or the 6174delT mutation. http://www.ncbi.nlm.nih.gov/pubmed/18439109

LISAMG · January 2010

Having pancreatic cancer in a family WITH breast or ovarian cancer CAN be a huge red flag for the BRCA2 gene, according to several documented research studies. This is why the specific question was asked if there was any BC, OVCA AND/OR Melanoma,,, or even Prostate Cancer has been shown to have a direct correlation with an underlying BRCA mutation. PC alone can also be suggestive of a BRCA association, especially with a young age of onset. Nothing else was implied, just for the record here.

As mentioned, genetic counseling should always be considered and/or explored in these given situations, as they are the only up-to-date professionals for accurate guidance. Too many healthcare professionals are NOT aware of possible correlations when obtaining/reviewing a patient's family history, unfortunately.

.Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683202/?tool=pubmed

Family history of pancreatic cancer in a high-risk cancer clinic: implications for risk assessment.

http://www.ncbi.nlm.nih.gov/pubmed/18581219?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed

"In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation."

This topic serves to remind me of a woman I cared for last year while working in the O.R. She was young and having back surgery. During her interview I learned she had BC a few years prior, Triple Negative BC, with no known history of BC or OVCA. She elaborated even more by telling me there was no cancer in her family EXCEPT her father who passed on from prostate ca. BINGO, a possible correlation...32 y old woman with TNBC, despite no known bc/ovca, with a father having prostate ca. I asked her if she ever considered genetic testing? She told me no one, including her oncologist or surgeons, ever suggested the idea. Long story short, I later learned this woman tested positive for BRCA2 and her sisters were in the process of being tested too.

leaf · January 2010

Having pancreatic cancer in a family WITH breast or ovarian cancer CAN be a huge red flag for the BRCA2 gene, according to research.

Yes, I agree, pancreatic cancer WITH bc and/or oc CAN be a huge red flag.

Quoting from your source, Although most pancreatic cancer is sporadic, 5-10% of cases show familial clustering http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683202/?tool=pubmed

which means that 90-95% of pancreatic cancer cases do not have KNOWN familial causes.

Genetic counseling and genetic testing is expensive, and not always covered by insurance, particularly if you have no family history. If Cameo had a first degree relative with breast cancer or ovarian cancer, you would think she would have mentioned this along with the news her father had pancreatic cancer. After all, Cameo mentioned pancreatic cancer on a breast cancer website.

Yes, it is possible to be BRCA positive and have NO cancer PERIOD in one's first or second degree relatives. I have read a post on this website from such a person. We have limited healthcare resources.

Everyone who gets breast cancer should NOT be BRCA tested. We would catch more people with BRCA that way, but it would not be a good spending of precious resources. Breast cancer (and ovarian) cancer are more likely to be flags for BRCA testing. That's why they included breast and ovarian cancer in the BRCA guidelines and did not include pancreatic cancer. Cameo says she has fibrocystic changes, not breast cancer.

vivre · January 2010

Barry, that was a great summary. Do you have the link? Thanks

CameoBarbie · January 2010

Thank you LISAMG and leaf.

I am grateful for the reading material. I certainly did not intend to discuss PC as such, but mostly about the BRCA2 gene. Thank you for sharing some knowledge of the subject.

I think, after reading the information you have provided, I will forward a letter to my Father's Doctor, to find out, if, I can, whether his illness was environmental or deeper. Maybe if they still have his records, I could find out some syncronicity or none at all. That is why I asked about it, as there isn't any history of BC or OVCA, nor Melanoma, that I know of, and since I don't understand it, it can be quite daunting.

You know I don't get any discussion time with my GP and I see her on Thursday. I guess I just want to know more than she is telling me, and if I stepped over the line on the board, I didn't mean to. I want her to hate me back with my "link to's" and I have another 6 months before pictures!

Like the 'link between menopause and histamines - (answer, Don't wear wool !!!)

Thank you ladies. Very appreciated.

LISAMG · January 2010

"Everyone who gets breast cancer should NOT be BRCA tested."

Of course not, but listed below are very real red flags for breast/ovarian cancer syndromes that can provoke the need for genetic counseling for those populations at high risk and/or may not be aware of a possible hereditary component in their family. I honestly believe advocacy & increasing awareness is so vitally important and worthy of mentioning here...that's all. Interestingly, many insurance companies will now pay for genetic testing WITHOUT a family history of BC/OVCA. This can be true, especially if a woman is diagnosed under the age of 50, a young woman diagnosed with triple negative bc and any woman with ovca [including women with no family history]. Based on current research findings, it is now being suggested that ANY woman at ANY age with a diagnosis of OVCA should consider BRCA testing. Hopefully, this will also soon become standard of care, as already recommended by many genetic counselors and/or gyn oncologists. OVCA is so lethal and very rare, but the consequences of ignoring potential future generations of devastation seems negligent, more deadly and even more costly. Prevention is the key and ultimately, more cost effective, bottom line.

Signs of an hereditary breast-ovarian cancer syndrome may include but are not limited to:

Breast cancer at age 45 or younger
Breast cancer in both breasts in a woman at any age
Both breast and ovarian cancer in the same woman
Two or more family members with ovarian cancer and/or breast cancer, especially if the breast cancer was diagnosed at or before age 50
At least one family member with breast cancer and one with ovarian cancer
Breast cancer in men
Ashkenazi Jewish heritage and ovarian cancer at any age or breast cancer before age 60
A number of relatives on the same side of the family with breast or ovarian cancer and one of these cancers:
- Prostate cancer
- Pancreatic cancer
- Melanoma

Other cancer syndromes can increase the risk for breast or ovarian cancer and may have other signs as well. To read more about these other syndromes, check out the source below:

http://www.facingourrisk.org/hereditary_cancer/hereditary_cancer_and_genetics.html?PHPSESSID=5c60251b4c9a30bb0e3a220743f3a2c6#signs

Niecee · January 2010

There is so much wonderful information in these posts, especially the lists of indications for genetic testing. Risk assessment is best done by meeting with a Certified Genetic Counselor who can review the family and personal histories and determine which test, if any, is appropriate. As stated above, not everyone with cancer in the family is a candidate for genetic testing. However, those of Ashkenazi Jewish ancestry need to be aware that they are more likely to carry a harmful gene mutation than non-Jews, and that with only one close relative with breast or ovarian cancer, their risk is increased. Sharsheret is an organization for Jewish women and families facing breast cancer. They have a great peer support program, a Genetics for Life program and many other free, confidential helpful resources. Feel free to call me at (866)474-2774. I also encourage you to visit our blog ,www.sharsheret.blogspot.com to learn more about out programs

Niecee Schonberger, MS, CGC

Genetics for Life Coordinator

Sharsheret

CameoBarbie · October 2010

Hello Everyone

Thought I would tell a bit more about this. I had a lipoma taken out 2 years ago. I read it is a tumor so I sought out info about benign tumors. In surfing I read about the BRCA2 mutation "referencing" markers and links, including pancreatic cancer. I asked and your response helped me and I have spent alot of time since then thinking about it or avoiding the subject.

(Let me first say that I learned of LISAMG's decision and I didn't want to bother her in such a personal time. My heart goes out to you.)

So, I will generalize as much as I can.

One precursor mentioned was "A NUMBER of relatives on the same side of the family with breast or ovarian cancer, and one of these cancers: prostate, pancreatic or melanoma."

I also said I would contact the Doctor who cared for my Father. Well, I did get the forms to submit to the "genetics academy" and had help filling it out but was stopped because I would have had to initiate contact with family members that would cause my Mother to need legal representation, over other issues. I received the letter in the mail saying when we would pursue it again to restart the process.
Also though, when I asked the Counsellor about this she referred me to a Nurse at her Center, who informed me that genetic testing is not granted when there is only one cancer in the family. Because on my Father's side there are 7 Uncles, and I Aunt who is fine, can't be sure of anything regarding women's cancers anyway. And besides, if anything changes with me, won't testing become a part of the procedure anyway?

So when does benign stay benign??????

I think I have to write to Dad's Doctor so that his records are not destroyed - just in case. That much I have to do.

CameoBarbie · April 2012

Well, it rears its ugly head. I have been sick with pneumonia again and a sinus infection and something weird growing on my eye that I have to have surgically cut off. It's been busy trying to keep up with stuff.

I had a catscan in March which luckily caught where the pneumonia was so am being taken care of well BUT the abdominal CT was prescheduled for something else and I was informed that they found cysts on my pancreas. Great. I am to have an MRI for that scheduled soon. Pancreatic cancer is what my Father passed from, so now, I don't know which one came first or if all of this is totally separate from the other.

I met some people last night while I was getting my coffee and she is expecting a BC diagnosis when she gets her CT. It was odd. I have wanted to blurt out all these health concerns to someone but you know, I did, to them, and it felt so good to discuss it face to face. She said she would pray for me! I really don't know what to expect from the MRI but most cysts on the pancreas are not so easily benign. Don't know where all this will lead.

pupmom · April 2012

Anecdotal, but, my dad died in his 90's of pancreatic cancer. My sister had DCIS in her 30's and my grandmother had BC, don't know its characteristics, in her 70's. I was 62 when diagnosed with BC. Because of my history I got the genetic testing. It was negative.

CameoBarbie · April 2012

I contacted that Dr that looked after my Dad but all the records were destroyed and he would not accept me as a patient. So, I have to start everything new. I think I will do what I can to assess future family member risk. All in all, something like ancestry.com but it can start with me for them.

I found this article. Role of BRCA1 and BRCA2 mutations in pancreatic cancer

Julia B Greer,
David C Whitcomb

Department of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

Correspondence to:
Dr J B Greer
Department of Medicine, University of Pittsburgh, Division of Gastroenterology, Hepatology and Nutrition, Presbyterian University Hospital, Mezzanine 2, C Wing, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA; julia.greer{at}verizon.net

Accepted 29 August 2006
Revised 25 August 2006
Published Online First 14 September 2006

Abstract

Germline mutations in the tumour suppressor genes breast cancer antigen gene (BRCA)1 and BRCA2 have been proven to portend a drastically increased lifetime risk of breast and ovarian cancers in the individuals who carry them. A number of studies have shown that the third most common cancer associated with these mutations is pancreatic cancer. BRCA1/2 mutations are characterised by "allelic" or "phenotypic" heterogeneity, in that they demonstrate differing cancer expressivity between and within pedigrees that segregate their mutations. If the same mutation is present in all our cells, why do some families with a given mutation display predominantly breast cancer? Why do other lineages show a preponderance of ovarian cancer? And why would some families have members who develop mostly or exclusively pancreatic cancer-a cancer that occurs more commonly in men and that lacks consistent evidence for a hormonal basis to its aetiology-which is clearly the case for breast and ovarian cancer? The answer is that other modifying genetic and environmental factors must interact to preferentially incite carcinogenesis in one organ over another. We are just beginning to elucidate what these factors are.

Until I get the MRI, I have my little place in now where land again. At least the scenery changed.

Cancer & risk factors by Mayo Clinic

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