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| Appolonia Baker Stoecklein She looks young, and I wonder if she's pregnant in this picture, perhaps with her first child, Cody. Photo credit: Annabelle Leyes Clinger |
My last post was about Appolonia Baker Stoecklein and her family background. I've been thinking about her recently because I'm grappling with her genetic legacy: gallbladder problems, and in particular, cancers of the biliary and digestive system (Spoiler: I don't have cancer!)
Appolonia died at the age of 41, after suffering for four years from an unknown disease. We don't know what that disease was - it could have been TB or MS - but if I had to guess, I'd say she died from some type of biliary cancer. Her descendants, certainly, have a sad history of succumbing to it. This type of medical history, in fact, is one of the practical applications of genealogy. It can be used for research on the genetic component of biliary cancers, and also as advanced warning for relatives.
What, exactly, is this family history?
First generation:
- Appolonia Baker Stoecklein died in 1895 after four years from an unknown wasting disease, possibly (although it is unproven) cancer. Age 41.
Second generation: Appolonia had three daughters.
- Her eldest, Cora Stoecklein, died of "stomach cancer" (no more specific information is available) in 1961, age 85.
- Her youngest, Irene Stoecklein Leyes (my direct maternal line great-grandmother) died of gallbladder cancer that spread to her liver, in 1967, age 76.
- Appolonia's middle daughter, Betty, died of a stroke.
Third generation: Appolonia had one granddaughter and one grandson.
- My maternal grandmother, Mary Jane Leyes Cunningham, died of gallbladder cancer that spread to the liver and other organs, in 1972, age 56.
- Her brother, Bill, died of lung cancer, unrelated to the biliary system
Fourth generation: Appolonia has seven great-grandaughters and two great-grandsons (I won't give the names for privacy reasons). Joyfully, all but one member of this generation are still alive.
- My own mother had her gallbladder removed at the age of 27 after developing gallstones during her first pregnancy. The surgeon found no signs of cancer.
- Sadly, my mother's first cousin died of bile duct cancer in 2013, at the age of 46.
Fifth generation: 11 male and 10 female descendants. I'm one of the older ones, and one of the few to have reached the "danger zone" of middle age (I'm 42). Although I've known since I was quite young that I needed to watch for signs of gallbladder stones, it wasn't until December that I first experienced the classic symptoms of a gallstone attack. I quickly made a doctor's appointment and presented the family history above, at which time the medical-industrial complex swung into high gear. (The doctors were pretty bowled over by the family history. They hadn't seen anything like it.) Because of the cancer risk, I had my gallbladder removed at the nearest big city research hospital, where they could remove it without rupturing it, rush it to pathology to check for cancer while I was still on the operating table, and then - if necessary - remove part of my liver and bile ducts if it turned out I had cancer.
I am very happy to say that the surgery went as well as possible, and I have no signs of cancer. I did, however, have two huge gallstones (one was 3.5cm long!), and the surgeon assures me I'll feel much better once I've healed. Now that I've done more research on gallstone symptoms, I realize that I've been feeling their effects for years, I just hadn't recognized the low-level and constant pain in my side and back as "gallbladder problems" as opposed to "back pain" or "acid reflex" or other issues. I'm very grateful to have this problem taken care of before it could become worse.
To summarize, of the six deceased individuals who are direct descendants of Appolonia Stoecklein, four of them died of cancers of the gallbladder, liver, "stomach", or bile system (all closely related organs). There is clearly a genetic component here, but what is it? It is unlikely to be a simple Mendelian trait, but rather a suite of multiple genes that create high risk for her descendants. The good news, then, is that a suite of genes is likely diluted with each generation.
Lynch Syndrome is one possible hereditary link to bile duct cancers. This syndrome was mentioned to my cousin and her sisters, when she was diagnosed with bile duct cancer. To say someone has "Lynch Syndrome" is to say they carry a dominant variant of one (or more) of five genes. These variants are associated with high risk for colon cancer, in particular, but also pancreas, endomitrium, and liver. These risks can be insanely high (much higher than usual when we say someone has a genetic risk for a particular cancer). For example, individuals have a 52-82% lifetime risk of colorectal cancer, with a mean age diagnosis of 44-61 years, and 30% of individuals are diagnosed before age 40(1). We'll know more about my particular Lynch Syndrome genes soon, but our family history differs from Lynch Syndrome in that most Lynch Syndrome cancers are associated with the colon, pancreas, endometrium, and ovaries. We do not seem particularly prone to cancer in those organs, but rather related organs, such as the liver and gallbladder.
The genes particularly associated with a high risk for bile duct cancer are only now being identified, although initial work suggests they aren't the same genes as those associated with Lynch Syndrome(3). Gallbladder cancer, in particular, is extremely rare, so little research has been done on its heritability. Most gallbladder cancer is caused by gallstones. The constant irritation of the organ by the stones can lead to out-of-control cell growth. Once possibility, then, is that Appolonia Stoecklein handed down genes that made her descendants more likely to develop gallstones, and in particular large gallstones, which are more highly correlated to cancer(2). Certainly, a combination of Lynch Syndrome genes, plus genes associated with the growth of large gallstones, could account for the particular patterns of cancer seen in our family.
As I said, we'll know more soon. I received a personal gene testing kit for Christmas, and the results are due any time now. I look forward to delving into the full data and seeing what I can find. In the meantime, I'd urge any descendants of Appolonia Stoecklein to consult with a doctor to schedule periodic scans of their liver and gallbladder. These are silent cancers, and by the time you're aware of the problem, it can be too late.
References:
(1) Kohlman, Wendy, and Stephen Gruber. 2014. Lynch Syndrome. http://www.ncbi.nlm.nih.gov/books/NBK1211/
(2) Lowenfels, A.B., et al. 1989. Gallstone Growth, Size, and Risk of Gallbladder Cancer: An Interracial Study. International Journal of Epidemiology 18:50-54. http://www.ncbi.nlm.nih.gov/pubmed/2722383
(3) Maroni, Luca, et al. 2013. The Significance of Genetics for Cholangiocarcinoma Development. Annals of Translational Medicine Oct: 28. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200671/
I am very happy to say that the surgery went as well as possible, and I have no signs of cancer. I did, however, have two huge gallstones (one was 3.5cm long!), and the surgeon assures me I'll feel much better once I've healed. Now that I've done more research on gallstone symptoms, I realize that I've been feeling their effects for years, I just hadn't recognized the low-level and constant pain in my side and back as "gallbladder problems" as opposed to "back pain" or "acid reflex" or other issues. I'm very grateful to have this problem taken care of before it could become worse.
To summarize, of the six deceased individuals who are direct descendants of Appolonia Stoecklein, four of them died of cancers of the gallbladder, liver, "stomach", or bile system (all closely related organs). There is clearly a genetic component here, but what is it? It is unlikely to be a simple Mendelian trait, but rather a suite of multiple genes that create high risk for her descendants. The good news, then, is that a suite of genes is likely diluted with each generation.
Lynch Syndrome is one possible hereditary link to bile duct cancers. This syndrome was mentioned to my cousin and her sisters, when she was diagnosed with bile duct cancer. To say someone has "Lynch Syndrome" is to say they carry a dominant variant of one (or more) of five genes. These variants are associated with high risk for colon cancer, in particular, but also pancreas, endomitrium, and liver. These risks can be insanely high (much higher than usual when we say someone has a genetic risk for a particular cancer). For example, individuals have a 52-82% lifetime risk of colorectal cancer, with a mean age diagnosis of 44-61 years, and 30% of individuals are diagnosed before age 40(1). We'll know more about my particular Lynch Syndrome genes soon, but our family history differs from Lynch Syndrome in that most Lynch Syndrome cancers are associated with the colon, pancreas, endometrium, and ovaries. We do not seem particularly prone to cancer in those organs, but rather related organs, such as the liver and gallbladder.
The genes particularly associated with a high risk for bile duct cancer are only now being identified, although initial work suggests they aren't the same genes as those associated with Lynch Syndrome(3). Gallbladder cancer, in particular, is extremely rare, so little research has been done on its heritability. Most gallbladder cancer is caused by gallstones. The constant irritation of the organ by the stones can lead to out-of-control cell growth. Once possibility, then, is that Appolonia Stoecklein handed down genes that made her descendants more likely to develop gallstones, and in particular large gallstones, which are more highly correlated to cancer(2). Certainly, a combination of Lynch Syndrome genes, plus genes associated with the growth of large gallstones, could account for the particular patterns of cancer seen in our family.
As I said, we'll know more soon. I received a personal gene testing kit for Christmas, and the results are due any time now. I look forward to delving into the full data and seeing what I can find. In the meantime, I'd urge any descendants of Appolonia Stoecklein to consult with a doctor to schedule periodic scans of their liver and gallbladder. These are silent cancers, and by the time you're aware of the problem, it can be too late.
References:
(1) Kohlman, Wendy, and Stephen Gruber. 2014. Lynch Syndrome. http://www.ncbi.nlm.nih.gov/books/NBK1211/
(2) Lowenfels, A.B., et al. 1989. Gallstone Growth, Size, and Risk of Gallbladder Cancer: An Interracial Study. International Journal of Epidemiology 18:50-54. http://www.ncbi.nlm.nih.gov/pubmed/2722383
(3) Maroni, Luca, et al. 2013. The Significance of Genetics for Cholangiocarcinoma Development. Annals of Translational Medicine Oct: 28. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200671/
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