First genetic link tied to Lobular | GLACIER study

JohnSmith

Last year, in April 2014, scientists presented results of GLACIER, a UK study of lobular breast cancer. They analyzed the DNA (SNPs = single nucleotide polymorphisms) of 6,539 ILC patients, including 436 cases of pure LCIS. They discovered six SNPs that were strongly associated with ILC and LCIS, but not with IDC, with the genetic variant "rs11977670" showing the strongest association. More specifically, women with rs11977670, were found to have a 13% higher chance of developing ILC than women without this variant. While this variant lives near the BRAF gene, the other SNPs associated with ILC included variants in the FGFR2 and MAP3K1 genes.
Interestingly, none of the 56 CDH1 SNPs analyzed showed significant association with lobular cancer, which is odd since the CDH1 gene encodes for E-cadherin, the hallmark of lobular lesions.
Also, analysis has shown for the first time that many of the SNPs that predispose to ILC also predispose to LCIS.

Since this study was conducted over 12 months ago, it would be interesting to see if this has led to identification of Lobular specific pathways.

Genetic predisposition to in situ and invasive lobular carcinoma of the breast

More detail:
These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4).
Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05.
Two SNPs showed significantly stronger associations for ILC than LCIS:
rs2981579 / 10q26 / FGFR2, P-het = 0.04
rs889312 / 5q11 / MAP3K1, P-het = 0.03);
and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04).

In addition, three of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology. Those showing stronger associations for ILC were:
rs11249433 / 1p11,
rs2981579 / 10q26 / FGFR2
rs10995190 / 10q21 / ZNF365

Full research report is here.

ingersollnic

Thanks John, that was an interesting journal article!

HopefulandScared

I wonder when that will be applied to breast panels. The panels I had drawn on June 4, 2015 had 17 genes. None were those.