Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

Background: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).

Methods: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study.

A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'-regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1). Genome-wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations.

Plasma folate concentrations are positively associated with risk of estrogen receptor beta negative breast cancer in a Swedish nested case control study.

Folate's role in breast cancer development is controversial. Not only estrogen receptor (ER) alpha status, but also ERbeta status of tumors may have confounded results from previous epidemiological studies. We aimed to examine associations between plasma folate concentration and postmenopausal breast cancer defined by ER status.

Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele.

Background: Folate is involved in DNA synthesis and methylation and may thereby influence carcinogenesis.

Objectives: We examined plasma folate (P-folate) concentration in relation to genotypes of the folate-metabolizing enzyme methylenetetrahydrofolate reductase [MTHFR 677C-->T (rs1801133) and 1298A-->C (rs1801131)]. We also explored whether P-folate was associated with risk of postmenopausal breast cancer overall and in subgroups with genetic variants of the MTHFR single nucleotide polymorphisms (SNPs).

Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the Malmö Diet and Cancer cohort.

Background: Single nucleotide polymorphisms (SNP) of the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) may modify associations between folate intake and breast cancer. We examined if the association between tertiles of dietary folate equivalents (DFE) and breast cancer was different in subgroups according to genotypes of the MTHFR 677 C>T (rs1801133) and 1298A>C (rs1801131) SNPs and if the polymorphisms per se were associated with breast cancer.

Methods: This nested case-control study included 544 incident cases with invasive breast cancer and 1,088 controls matched on age and blood sampling date from the population-based Malmö Diet and Cancer cohort.

The protective association of high plasma enterolactone with breast cancer is reasonably robust in women with polymorphisms in the estrogen receptor alpha and beta genes.

It is plausible that polymorphisms in the estrogen receptor alpha and beta genes (ESR1 and ESR2) may modulate the association between enterolactone and breast cancer. Seven polymorphisms in ESR1 (rs827422, rs1709184, rs2347867, rs3020328, rs72207, rs2982896, and rs2234693) and 5 polymorphisms in ESR2 (rs915057, rs1269056, rs1256033, rs3020450, and rs3020443) were selected. The risk of breast cancer for these polymorphisms was estimated among 542 cases and 1076 matched controls from the population-based Malmö Diet and Cancer cohort.