Loss-of-Function Variants Associated with Gastric Cancer Risk

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Loss-of-function mutations in ATM were associated with an increased risk for developing gastric cancer, according to an article published online in the journal Nature Genetics.

A Genome-wide association study (GWAS) in a European population with information on 2,500 cases of gastric cancer and 205,652 controls was reported. 

The authors found a new association between gastric cancer and the loss-of-function mutations in ATM gene test, P = 8.0 × 10−12; OR = 4.74).    Patients carrying the loss-of-function mutations were diagnosed with cancer significantly earlier in age than those not carrying the variations.

Furthermore, a combination of the loss-of-function mutations p.Gln852, p.Ser644, and p.Tyr103 (combined minor allele frequency (MAF) = 0.3%) were linked with pancreatic (OR = 3.81) and prostate (OR = 2.18) cancer and indicated a risk of breast (OR = 1.82) and colorectal (OR = 1.97) cancer.

Results confirmed a relationship between the three loci associated with gastric cancer in Asia (MUC1PRKAA1 and PSCA) and gastric cancer in Europeans.

Women who survive breast cancer may have a higher-than-average risk of developing thyroid cancer in
Loss-of-function mutations in ATM were associated with an increased risk for developing gastric cancer.
Hannes Helgason, Kari Stefansson and colleagues report an association study of gastric cancer susceptibility based on whole-genome sequencing in the Icelandic population. They find that loss-of-function variants in ATM confer risk of gastric cancer.
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