維他命D基因變化與大腸癌風險較高有關


  【24drs.com】維他命D路徑的基因變化,可能會造成美國黑人的大腸直腸癌風險增加。根據發表於美國癌症研究研討會、針對跨領域癌症健康科學的研究,雖然需要更多資料,DNA序列的差異顯然改變了維他命D相關基因的功能。
  
  研究者發現,維他命D相關基因之多種單一核甘酸多型性(SNPs)造成黑人的易感性增加,不過,一個次要對偶基因對左側大腸直腸癌有某種程度的保護作用。
  
  伊利諾大學博士後研究助理Fabio Pibiri博士表示,血清維他命D值較高和大腸直腸癌比率較低有關。維他命D因日曬而活化,而皮膚色素增加會降低紫外線穿透皮膚的量,黑人比白人更容易缺乏維他命D。這也解釋了美國黑人為什麼比白人有更高的發病率和死亡率。
  
  研究顯示,基因差異可能有重要影響。Pibiri博士在發表前的記者會中公佈資料。
  
  Pibiri博士等人在他們的研究中評估了39種SNPs和維他命D相關基因(CYP27A1、GC、CYP3A4、CYP2R1、DHCR7/NADSYN1、VDR、CYP27B1與CYP24A1)之DNA序列變化。研究對象是961名大腸直腸癌黑人病患,838名黑人對照組。
  
  使用邏輯回歸計算勝算比(OR),設定一個累加基因模式,並且校正年紀、性別與西非組先等因素。進行後續分析確認基因多態性是否造成右側或左側大腸直腸癌(包括直腸癌)的風險差異。
  
  大腸直腸癌和24-hydroxylase基因CYP24A1、rs73913755的SNPs(OR,0.73;P= .0003)之間有些微關聯,這基因負責降解calcidiol,至於25-hydroxylase基因CYP2R1、rs12794714 (OR,0.82;P= .032)則是將cholecalciferol轉化成calcidiol。
  
  Pibiri博士指出,左側和右側腫瘤之間有差異。腫瘤的特徵不同,黑人病患左側腫瘤比率比白人低。就我們的分析,這有其關聯,其中1種SNPs看來提供了某種保護力。
  
  右側疾病和SNPs無關。不過,有4種SNPs和左側疾病有關。2種SNPs是維他命D–連結蛋白質基因GC — rs1155563 (OR,0.77;P= .039)和rs16847024 (OR,1.56;P= .003),2個是在24-hydroxylase基因CYP24A1 — rs6022990 (OR,1.48;P= .006)與rs73913755 (OR,0.67;P= .0002)。
  
  校正多元檢測之後,發現rs73913755和左側疾病顯著有關。
  
  Pibiri博士指出,需要更多資料來證明DNSA序列之差異改變了維他命D相關基因的功能。
  
  約翰霍普金斯大學Sidney Kimmel綜合癌症中心主任William Nelson博士表示,維他命D的傳說已經由來已久。他質疑這項研究是否對此特定補充品提供了合理原因。他問道,有這些特定SNPs的黑人病患比較可能會發生大腸直腸癌,所以我們應該要測量維他命D值,如果偏低,就加以補充嗎?
  
  Pibiri博士回應時指出,維他命D補充品可能有點類似癌症的標靶治療,某些人可能可受益於特定治療;測量濃度與補充品對於居住在北部地區的黑人而言,可能是個好主意。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6956&x_classno=0&x_chkdelpoint=Y
  

Vitamin D Gene Variations Linked to Higher Risk for Colon Cancer

By Roxanne Nelson
Medscape Medical News

Genetic variants in the vitamin D pathway might contribute to an increased susceptibility to colorectal cancer in black Americans. Although more data are needed, it appears that differences in the DNA sequence alter the function of the vitamin D–related genes, according to research presented at the 5th American Association for Cancer Research Conference on the Science of Cancer Health Disparities, being held in San Diego, California.

The researchers found that several single-nucleotide polymorphisms (SNPs) in vitamin D–related genes contribute to an increase in susceptibility in blacks, although a minor allele gives some degree of protection against left-sided colorectal cancer.

Higher levels of serum vitamin D have been linked to a lower rate of colorectal cancer, said Fabio Pibiri, PhD, a postdoctoral associate at the University of Illinois at Chicago. Vitamin D is activated by sun exposure, and because increased skin pigment lowers the amount of ultraviolet light that can penetrate the skin, more blacks than whites are deficient in vitamin D, he explained. This explains the higher incidence and mortality in black than in white Americans, he noted.

"Our research showed that genetic differences may play an important role as well," he added. Dr. Pibiri presented the data at a press briefing held in advance of his presentation.

Study Details

In their study, Dr. Pibiri and colleagues evaluated 39 SNPs and DNA sequence variations in vitamin D–related genes (CYP27A1, GC, CYP3A4, CYP2R1, DHCR7/NADSYN1, VDR, CYP27B1, and CYP24A1). Study participants were 961 black patients with colorectal cancer and 838 black control subjects from the North Carolina Colorectal Cancer Study and the Chicago Colorectal Cancer Consortium.

Logistic regression was used to calculate odds ratios (OR), assuming an additive genetic model, after adjustment for age, sex, and West African ancestry. Further analyses were conducted to determine whether genetic polymorphisms confer a differential risk for right-sided or left-sided colorectal cancer (including rectal cancer).

Nominal associations were found between colorectal cancer and SNPs in the 24-hydroxylase gene CYP24A1, rs73913755 (OR, 0.73; P= .0003), which is responsible for the degradation of calcidiol, and in the 25-hydroxylase gene CYP2R1, rs12794714 (OR, 0.82; P= .032), which converts cholecalciferol into calcidiol.

Left-Side Protection

Dr. Pibiri noted the difference between left- and ride-sided tumors. "The characteristics of the tumors are different, and [black patients] have a lower proportion on the left side than whites," he said. "From our analysis, there is a correlation. One of the SNPs appears to offer some protection."

There were no SNPs associated with right-sided disease. However, 4 SNPs were associated with left-sided disease. Two SNPS were in the vitamin D–binding protein gene GC — rs1155563 (OR, 0.77; P= .039) and rs16847024 (OR, 1.56; P= .003) — and 2 were in the 24-hydroxylase gene CYP24A1 — rs6022990 (OR, 1.48; P= .006) and rs73913755 (OR, 0.67; P= .0002).

After adjustment for multiple testing, rs73913755 was found to be significantly associated with left-sided disease.

Dr. Pibiri noted that more data are needed to prove that differences in the DNA sequence alter the function of vitamin D–related genes.

Supplementation Needed?

"The vitamin D story has been 'percolating' for a long time," said William Nelson, MD, PhD, director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Maryland.

He wonders whether this study provides a rationale for targeted supplementation. Black patients "with these particular SNPs might be prone to developing colorectal cancer, so should we be measuring vitamin D levels and, if they are low, supplementing them?" he asked.

In response, Dr. Pibiri pointed out that vitamin D supplementation might be similar to targeted therapies in cancer; certain populations can benefit from specific treatments. Measuring levels and supplementing might be a good idea for black people who live in northern climates, he said.

Dr. Pibiri and Dr. Nelson have disclosed no relevant financial relationships.

5th American Association for Cancer Research Conference on the Science of Cancer Health Disparities. Presented October 18, 2012.

    
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