A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis

نویسندگان

  • Sanford D. Markowitz
  • Nora L. Nock
  • Stephanie L. Schmit
  • Zsofia K. Stadler
  • Vijai Joseph
  • Lu Zhang
  • Joseph E. Willis
  • Peter Scacheri
  • Martina Veigl
  • Mark D. Adams
  • Leon Raskin
  • John F. Sullivan
  • Kelly Stratton
  • Jinru Shia
  • Nathan Ellis
  • Hedy S. Rennert
  • Christopher Manschreck
  • Li Li
  • Kenneth Offit
  • Robert C. Elston
  • Gadi Rennert
  • Stephen B. Gruber
  • Ajay Goel
چکیده

We tested for germline variants showing association to colon cancer metastasis using a genome-wide association study that compared Ashkenazi Jewish individuals with stage IV metastatic colon cancers versus those with stage I or II non-metastatic colon cancers. In a two-stage study design, we demonstrated significant association to developing metastatic disease for rs60745952, that in Ashkenazi discovery and validation cohorts, respectively, showed an odds ratio (OR) = 2.3 (P = 2.73E-06) and OR = 1.89 (P = 8.05E-04) (exceeding validation threshold of 0.0044). Significant association to metastatic colon cancer was further confirmed by a meta-analysis of rs60745952 in these datasets plus an additional Ashkenazi validation cohort (OR = 1.92; 95% CI: 1.28-2.87), and by a permutation test that demonstrated a significantly longer haplotype surrounding rs60745952 in the stage IV samples. rs60745952, located in an intergenic region on chromosome 4q31.1, and not previously associated with cancer, is, thus, a germline genetic marker for susceptibility to developing colon cancer metastases among Ashkenazi Jews.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Association of a New Germline Variant in the MUTYH DNA Glycosylase Gene with Colorectal Adenoma Transformation into Malignancy

Background: MUTYH DNA glycosylase germline mutations are linked to the recessive inheritance of multiple adenoma. Studies have revealed that germline mutations in this gene are ethnicity related. This study aimed to identify the germline mutations in MUTYH gene and determine their prevalence among Jordanian patients with colorectal adenoma. Methods: In this study, 150 colorectal adenoma patient...

متن کامل

The Report of KRAS Mutation and NRAS Wild-Type in a Patient with Thyroid Metastasis from Colon Cancer: a Rare Case Report

Colorectal cancer (CRC) metastasis to the thyroid gland is rare. Here wereport a 45 yr-old man in western Iran referred to Hematology Clinic, Kermanshah city, Iran in March 2014 with complaint of exertional dyspnea, multi-nodular goiter as well as complaint of exertional dyspnea, and multi-nodular goiter. His history included a low anterior resection of rectum in 9 months ago for a high-risk st...

متن کامل

8q24 Cancer Risk Allele Associated with Major Metastatic Risk in Inflammatory Breast Cancer

BACKGROUND Association studies have identified low penetrance alleles that participate to the risk of cancer development. The 8q24 chromosomal region contains several such loci involved in various cancers that have been recently studied for their propensity to influence the clinical outcome of prostate cancer. We investigated here two 8q24 breast and colon cancer risk alleles in the close vicin...

متن کامل

عوامل مؤثر بر بقاء بیماران مبتلا به سرطان کولورکتال با استفاده از توابع مفصل

Background & objectives: Competing risk data is one of the multivarite survival data. Competing risk data can be modelled using copula function. In this study we propose a bayesian modelling approach of competing risk data using the copula function.Methods: We used the data from colorectal cancer registyrarty in Tehran. After constructing likelihood function using Clayton copula by choosing app...

متن کامل

Metastasis of Colon Adenocarcinoma to Maxillary Gingiva and Palate

Introduction: Colon adenocarcinoma is one of the foremost causes of cancer mortality. Oral metastasis of colon adenocarcinoma is, however, rare and indicates an end-stage disease process.   Case Report: We report a case of a 69-year-old female with a gingival mass diagnosed with colon adenocarcinoma and liver metastasis after one year. A swelli...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2016