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Despite high screening rates, breast cancer disparities persist among women veterans because of occupational risks and barriers to access. Three essential bills recently passed in Congress seek to expand access to breast cancer screenings and cancer care within the Veterans Health Administration. The Making Advances in Mammography and Medical Options for Veterans Act expands screening via partnerships with the National Cancer Institute, integrating telescreening and upgrading imaging technology. The Dr. Kate Hendricks Thomas Supporting Expanded Review for Veterans In Combat Environments Act broadens eligibility for those exposed to toxins and personalized risk assessments. The bipartisan Sergeant First Class Health Robinson Honoring our Promise to Address Comprehensive Toxics Act extends benefits for toxin-exposed veterans with presumptive conditions, including breast cancer. Further programs such as National TeleOncology, the Breast & Gynecologic Oncology System of Excellence, and research collaborations between the Veterans Health Administration, National Cancer Institute, and Surveillance, Epidemiology and End Results Program seek to improve access, enhance understanding and care for women veterans with cancer, and mark significant progress in comprehensive care. [ABSTRACT FROM AUTHOR]

O-6-methylguanine-DNA methyltransferase (MGMT) repairs inappropriately methylated guanine residues in DNA. MGMT promoter methylation and gene silencing are common events in colorectal cancer, and may or may not co-exist with the CpG island methylator phenotype (CIMP). To date, no study has examined the relationship between MGMT promoter methylation and common MGMT single nucleotide polymorphisms (SNPs), which have been associated with colorectal cancer risk. Utilizing real-time polymerase chain reaction (MethyLight technology), we quantified DNA methylation in MGMT and eight other markers (a CIMP diagnostic panel including CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1 in 182 colorectal cancers collected from two prospective cohorts, the Nurses’ Health Study and the Health Professionals Follow-up Study. We genotyped four MGMT germline SNPs in normal DNA and assessed microsatellite instability (MSI), 18q loss of heterozygosity and KRAS and BRAF status in tumors. The presence of a common MGMT promoter SNP (NM_002412.2:c.-56C>T) (rs16906252) was strongly associated with MGMT methylation (multivariate odds ratio 18.0; 95% confidence interval, 6.2–52.1, P < 0.0001). The presence of the c.-56C>T SNP was also associated with loss of MGMT expression in tumors (assessed by immunohistochemistry) (P = 0.009). This promoter SNP was not correlated with KRAS, BRAF, CIMP or MSI status. None of the other three non-promoter SNPs was significantly associated with any molecular changes tested. In conclusion, we have found a strong association between the germline polymorphism (c.-56C>T) of the MGMT promoter and promoter methylation/silencing of MGMT in colorectal cancer. Our data provide compelling evidence for common susceptibility for MGMT promoter CpG island methylation. [ABSTRACT FROM AUTHOR]

Dietary folate and alcohol consumption as well as polymorphic variants in one-carbon metabolism genes may modulate risk of colorectal adenoma through aberrant DNA methylation and altered nucleotide synthesis and repair. We assessed the association of 24 non-synonymous single nucleotide polymorphisms (nsSNPs) in 13 genes in the one-carbon metabolism pathway and risk of colorectal adenoma in 556 incident cases and 557 controls nested in the Nurses Health Study. Most of the SNPs were not associated with risk of colorectal adenoma. We did, however, observe a modest increased risk among carriers of the transcobalamin (TCN) II 259 Pro/Arg + Arg/Arg variant (odds ratio 1.48, 95% confidence interval 1.09–2.02) for colorectal adenoma. The TCN II Pro259Arg polymorphism may affect TCN binding and transport of vitamin B12 and thus warrants further investigation of its biological function. In addition, the methionine synthase reductase (MTRR) Arg415Cys and MTRR Ser284Thr variant carriers, also in the vitamin B12 pathway, have suggestive associations with advanced colorectal adenoma (defined as being larger than 1 cm, villous, tubular–villous or carcinoma in situ histology). We observed significant evidence for departure from multiplicative interaction for the betaine–homocysteine methyltransferase (BHMT) Arg239Gln with dietary methyl status (based on intake of dietary folate, methionine and alcohol intake) in relation to colorectal adenoma; no such interaction was observed for the other 23 SNPs. Further investigation is required to validate the association of the polymorphisms in the one-carbon metabolic genes and risk of colorectal adenoma. [ABSTRACT FROM AUTHOR]