Additionally, we summarized breast cancer risk associated with the following genetic factors: breast cancer susceptibility high-penetrance genes (BRCA1, BRCA2, p53, PTEN, ATM, NBS1 or LKB1) and low-penetrance genes such as cytochrome P450 genes (CYP1A1, CYP2D6, CYP19), glutathione S-transferase family (GSTM1, GSTP1), alcohol and one-carbon metabolism genes (ADH1C and MTHFR), DNA repair genes (XRCC1, XRCC3, ERCC4/XPF) and genes encoding cell signaling molecules (PR, ER, TNFalpha or HSP70).
To our knowledge, we are the first to show that a germline mutation causing PJS is combined with the loss of the homologous normal allele of LKB1/STK11 in breast cancer.
We conclude that 19p13.2-13.3 allele loss is a common event in the pathogenesis of breast carcinoma that often involves discontinuous LOH of multiple, localized TSGs (including LKB1), the concurrent inactivation of which may contribute to breast cancer progression.
It is estimated that 5%-10% of all breast cancers in women are associated with hereditary susceptibility due to mutations in autosomal dominant genes, such as BRCA1 and BRCA2, p53, pTEN, and STK11/LKB1.
Of 40 informative primary breast cancers, 3 showed loss of heterozygosity on chromosome 19p in the vicinity of LKB1, and no somatic mutations of LKB1 were observed in 62 primary breast cancers and 17 established breast cancer cell lines.
Genes underlying these cancers are now recognized in colorectal cancer (APC, mismatch repair genes, LKB1) and in breast cancer (BRCA1, BRCA2) whereas, in prostate cancer, a locus in chromosome 1 (HPC1) has been proposed on the basis of linkage analysis.