rs351855

rs351855, a SNP in the fibroblast growth factor receptor 4 (FGFR4) gene, is also known as the Gly388Arg variant. The rs351855(T) allele encodes the risk (Arg) allele. The Arg form of this SNP is likely to cause a harder to treat version of node-positive breast cancer, including reducing the efficacy of Herceptin, based on a study of 372 patients. A study of ~500 Japanese prostate cancer patients found that individuals with a rs351855(T;T) genotype had a 2.2- and 1.9-fold increased risk of prostate cancer and benign prostate hyperplasia (BPH), and a 1.8-fold increased risk of metastatic prostate cancer compared to the (C;C) genotype. A meta-analysis published in 2011, surveying a total of 2,618 cases of prostate cancer, concluded that the odds ratio per rs351855(T) allele was 1.17 (CI: 1.07 - 1.29), and that when stratified by race, Caucasians and Asians were at highest risk. ~1500 prostate cancer patients showed only a weak association between rs351855 and prostate-cancer specific mortality, and no evidence associating it with prostate cancer risk, disease aggressiveness, Gleason score, or stage.

A;A

This SNP is part of several polygenic risk scores for breast cancer, so in that sense it's "valid" but as a stand-alone SNP it's not of much clinical consequence. This rare genotype of the fibroblast growth factor receptor 4 gene influences several forms of cancer progression and tumor cell motility. It is found in ~3% of people. It is unlikely that any clinician person would take any action on this alone. As a risk factor for breast or prostate cancer in people with Asian ancestry, it seems to increase risk by ~ 1.2x.