關於 genetic predisposition ，我們在網路上蒐集到這些相關的討論、資訊與評價

上個月是世界乳癌月，因為有乳癌基因BRCA1與BRCA2的突變（統稱BRCA) 而做預防性乳房切除的議題再次被討論。女性大眾一生中約有八分之一的機率會得到乳癌，如果不幸有 BRCA 基因突變的女性則約有 80% 的機率會得乳癌 。（40% 的機率得卵巢癌）

很顯然有這個基因突變會大幅增加得到乳癌的機率。再者，有突變病人的乳癌比其他人更難治療也更容易復發。影星安潔莉娜∙裘莉就是因爲有這個基因的突變而決定做預防性的全乳房與卵巢切除。但為什麼各國的婦產科醫學會大都不推薦所有女性做BRCA 突變的檢測？ 早點知道基因檢測的結果會有壞處嗎？我自己尋找資料後希望與各位分享我的想法，希望大家能更了解這個題目。

基因是人體細胞內含的遺傳資訊單位，它像是身體裡的零件製造代碼，代碼寫錯時做出來的零件就會有問題，而代碼的儲存媒介是雙股DNA，它像拉鏈一樣接合以便保存遺傳資訊，待基因需要表現時細胞會把DNA像拉鏈一樣拉開，轉錄為mRNA 最終轉譯為蛋白質，而各種不同的蛋白質表現成了各種細胞的變化，形成外在人與人之間不同的表現 如酒渦或髮線。（可惜的是我兩者都沒有）顯性的基因變化代表只要從父母任一方遺傳到這個變化便會表現出來，隱性的基因變化代表必需從父母雙方都遺傳到這個變化才會表現出來。BRCA 屬於顯性基因。

健康BRCA基因製造的蛋白質可以抑制細胞不正常的增生而突變的結果，造成所製造的蛋白質無法有效的抑制細胞增生進而產生癌症，約400個人就有一個帶有此突變，對個人來說，只要花幾千塊可以找到這個高度致癌因子是否存在有何不可？在美國婦產科學會的調查中，只有40% 的醫生認為每位女性都可以做 ，我認為原因在於檢測結果的後續行動，在目前的科技下還沒有專家們明確的共識。 雖然有些方法可以降低BRCA突變病人發生乳癌的風險（如吃藥或手術）姑且不論這些方法本身含有的風險，但陽性不代表一定會得乳癌，而陰性也不代表得乳癌的機率會大幅降低。 (約90% 的乳癌病人都沒有BRCA突變) 所以尤其是對於無其他風險的健康女性來說 ，檢測結果背後意義，其複雜度與心理負擔遠比一般的抽血(如膽固醇檢測) 來的大許多，而其必要性也可受討論。

目前國際上的共識是除了需要詳盡的檢測前基因諮詢外，也建議已經有其他危險因子，如家族史 年齡早發(50歲前)乳癌，同患乳癌與卵巢癌的病人考慮做基因檢測，才會有比較大的幫忙。希望這些想法能幫助考慮做乳癌基因檢測的各位做參考，有不詳盡的方面也請多包涵。

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The breast cancer genes BRCA1 and 2 (BRCA) made its biggest fame with Angelina Jolie’s decision to undergo preventive breast and ovary surgical removal after learning she carries a pathogenic mutation of BRCA. There is about a 1 in 8 chance of getting breast cancer in a woman’s lifetime. With the BRCA mutations, the risk of developing breast cancer can be as high as 80%. (and about 40% chance of developing ovarian cancer).

Having a pathogenic mutation in BRCA greatly increases the risk of developing breast cancer (and ovarian cancer). Moreover, breast cancer in patients with BRCA mutation tends to be more aggressive and more likely to recur. It seems intuitive to screen for BRCA mutation in every woman. However, most professional bodies around the world do not recommend routine BRCA testing because the carrier rate is low (approximately 0.25% in the general population). Also, there is no conclusive evidence on non-surgical methods of risk reduction. (Hormone antagonists such as Tamoxifen has only been shown to reduce breast cancer in the general population but not patients with BRCA mutation)

Prophylactic mastectomy and oophorectomy is very effective at reducing the risk of breast ( 50% reduction) and ovarian cancer (80% reduction) in patients with BRCA mutation, although the risk is not completely eliminated. However, not everyone who carries the BRCA gene will develop breast/ovarian cancer, so there is potentially an unnecessary surgical risk if one chooses to undertake prophylactic surgery.

Pre-test genetic counselling should be considered in everyone who wishes to take the BRCA testing. Currently the recommendation for women is those who have a strong family history of breast cancer, breast cancer younger than 50 years of age or patients with both breast and ovarian cancer.

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BRCA: The Breast Cancer Gene [Internet]. National Breast Cancer Foundation. [cited 2020 Nov 29]. Available from: https://www.nationalbreastcancer.org/what-is-brca/

Kim E-K, Park SY, Kim S-W. Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients. J Pathol Transl Med. 2020 May 14;54(4):265–75.

Hung F-H, Wang YA, Jian J-W, Peng H-P, Hsieh L-L, Hung C-F, et al. Evaluating BRCA mutation risk predictive models in a Chinese cohort in Taiwan. Scientific Reports. 2019 Jul 15;9(1):10229.

Sung P-L, Wen K-C, Chen Y-J, Chao T-C, Tsai Y-F, Tseng L-M, et al. The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels. PLOS ONE. 2017 Sep 29;12(9):e0185615.

"You are what you eat" - have you heard of that? What about when you're pregnant? Would your baby "become" what you eat? Fact is, your genetic predisposition, activity level and your diet during pregnancy would definitely affect how your baby will turn out to be. I spoke about this in length in my podcast before I "popped". Check out episode 97 entitled "I Got It From My Mama" 👉 https://www.aiskacang.com.my/b-fit-b-cool/

不能胖才是大麻煩

Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase).

We all have a genetic predisposition to the amount of fat mass that we can safely achieve..Some folks have a very limited ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue. The recruitment of new adipose cells is known as Adipogenesis.

Adipogenesis is the process of cell differentiation by which pre-adipocytes become adipocytes. Once these folks can no longer recruit new adipose cells to store excess lipids during times of over-feeding, their existing adipocytes (fat cells) in their fat mass, their adipocytes grow in cell size and they reach a point where they become hypertrophic.

Their adipocytes (fat cells) become very inflamed, very insulin resistant. They start leaking all kinds of inflammatory markers into the circulation. These adipocytes (fat cells) become so insulin resistant that they can no longer properly regulate the flow of fatty acids and glycerol from storage. There is an excess spill-over of fatty acids to the liver. These excess fatty acids are re-esterfied in the liver to triglycerides. These excess fatty acids and triglycerides cause extreme insulin resistance in the liver. They also cause fatty liver. There is a dramatic rise in circulating triglycerides (lipids). These excess lipids also end up stored in the pancreas and other organs causing lipotoxicity. Welcome to T2 diabetes.

"Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lipotoxicity is believed to have a role in heart failure, obesity, and diabetes, and is estimated to affect approximately 25% of the adult American population."
https://en.wikipedia.org/wiki/Lipotoxicity .

Folks that have metabolically health fat mass have adipose tissue that grows by hyperplasia, increase in cell number..

Adiponectin is a very important hormone that is secreted by our adipose tissue..Adiponectin is very insulin sensitizing...also increases our metabolic rate...increases fatty acid oxidation...preserves pancreatic beta-cells...adiponectin promotes glucose-stimulated insulin secretion (GSIS), prevents apoptosis (cell death), and enhances the viability of pancreatic beta-cells under a variety of conditions.

Once you have dysfunctional adipose tissue, your adipocytes release LESS adiponectin and more leptin..Adiponectin is very anti-inflammatory...Leptin is very PRO-inflammatory.

LOW blood adiponectin levels are VERY indicative of T2 diabetes and fatty liver, many other diseases.

Small healthy fat cells release very high levels of adiponectin, very low levels of leptin..

I would need to try and write a few posts about adiponectin, T2D and fatty liver..

Here is a good article on adiponectin:

"Ever since its initial discovery, adiponectin has inspired widespread interest. Readily detectable in blood, stable upon collection and relatively inert to the method of collection and diurnal changes, its levels inversely correlate with multiple metabolic disorders and related diseases. Adiponectin can therefore serve as a potent clinical biomarker in humans and rodents. From the 10,000 studies over the past two decades since its discovery, it is widely appreciated that adiponectin exerts pleiotropic metabolic effects. Adiponectin sensitizes peripheral tissues to insulin and protects against inflammation and apoptosis."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773837/ .

Kobe beef (神戸ビーフ Kōbe bīfu) (KO-BEH) refers to beef from the Tajima strain of Wagyu cattle, raised in Japan's Hyogo Prefecture according to rules as set out by the Kobe Beef Marketing and Distribution Promotion Association. The meat is a delicacy renowned for its flavor, tenderness, and fatty, well-marbled texture. Kobe beef can be prepared as steak, sukiyaki, shabu shabu, sashimi, and teppanyaki. Kobe beef is generally considered one of the three top brands (known as Sandai Wagyuu, "the three big beefs"), along with Matsusaka beef and Ōmi beef or Yonezawa beef.

Kobe beef is also called Kobe niku (神戸肉, "Kobe meat"), Kobe-gyu (神戸牛) or Kobe-ushi (神戸牛, "Kobe cattle") in Japanese.

Wagyu (和牛 Wagyū, "Japanese cow") is any of four Japanese breeds of beef cattle, the most desired of which is genetically predisposed to intense marbling and to producing a high percentage of oleaginous unsaturated fat. The meat from such wagyu cattle is known for its quality, and commands a high price. In several areas of Japan, wagyu beef is shipped carrying area names. Some examples are Matsusaka beef, Kobe beef, Yonezawa beef, Mishima beef, Omi beef and Sanda beef.

There are four breeds of wagyu: Japanese Black (黒毛和種 Kuroge Washu), Japanese Brown (赤毛和種 Akage Washu or Akaushi), Japanese Polled (無角和種 Mukaku Washu), and Japanese Shorthorn (日本短角和種 Nihon Tankaku Washu). Wagyu cattle's genetic predisposition yields a beef that contains a higher percentage of omega-3 and omega-6 fatty acids than typical beef. The increased marbling also increases the ratio of monounsaturated fats to saturated fats.

Japanese Black makes up 90% of all fattened cattle in Japan. Strains of Japanese Black include Tottori, Tajima, Shimane and Okayama. Japanese Brown, also known as Japanese Red, is the other main breed; strains include Kochi and Kumamoto. Japanese Shorthorn makes up less than one percent of all cattle in Japan.