Low 25-Hydroxyvitamin D and Myofascial Pain: Association of Cancer, Colon Polyps, and Tendon Rupture.

BACKGROUND: Myofascial pain that has been associated with cancer and increased risk of morbidity and mortality in cancer patients is intrinsically associated with low magnesium and low 25-hydroxyvitamin D (25(OH)D). Therefore, this physical finding was used as a clinical diagnostic proxy. OBJECTIVE: The objective of this study was to assess the association and prevalence of disease in individuals with myofascial pain and low 25(OH)D in a county with low magnesium in the drinking water. DESIGN: This is a retrospective cross-sectional study of a chart review of 269 subjects to assess subjects presenting with myofascial pain (assessed by tender trigger points) and 25(OH)D concentrations below 30 ng/mL or a history of 25(OH)D deficiency compared to those without these exposures. RESULTS: The association between the exposure of low 25(OH)D levels and myofascial pain was compared to all cancers, colon polyps, and tendon ruptures. The odds of having cancer with the combined exposures was 10.14 times the odds of not having either exposure (95% confidence interval [CI], 5.08, 20.25, p < 0.001). For adenomatous colon polyps, the odds ratio (OR) was 7.24 (95% CI, 3.83, 13.69, p < 0.001), and for tendon rupture, the OR was 8.65 (95% CI, 3.76, 19.94, p < 0.001). Of 80 subjects who had both myofascial pain and 25(OH)D less than 30 ng/mL, 74 were tested for red blood cell (RBC) magnesium. Half of those subjects had RBC magnesium concentrations < 4.6 mg/dL, and 23% had levels below the reference range (4.0-6.4 mg/dL). CONCLUSION: Myofascial pain as assessed by tender trigger points and 25(OH)D deficiency showed a significant association with cancer, adenomatous colon polyps, and tendon rupture. Further studies to verify these results are needed, especially in areas where there is low magnesium in the drinking water.

A steroid metabolizing gene variant in a polyfactorial model improves risk prediction in a high incidence breast cancer population.

BACKGROUND: We have combined functional gene polymorphisms with clinical factors to improve prediction and understanding of sporadic breast cancer risk, particularly within a high incidence Caucasian population. METHODS: A polyfactorial risk model (PFRM) was built from both clinical data and functional single nucleotide polymorphism (SNP) gene candidates using multivariate logistic regression analysis on data from 5022 US Caucasian females (1671 breast cancer cases, 3351 controls), validated in an independent set of 1193 women (400 cases, 793 controls), and reassessed in a unique high incidence breast cancer population (165 cases, 173 controls) from Marin County, CA. RESULTS: The optimized PFRM consisted of 22 SNPs (19 genes, 6 regulating steroid metabolism) and 5 clinical risk factors, and its 5-year and lifetime risk prediction performance proved significantly superior (~ 2-fold) over the Gail model (Breast Cancer Risk Assessment Tool, BCRAT), whether assessed by odds (OR) or positive likelihood (PLR) ratios over increasing model risk levels. Improved performance of the PFRM in high risk Marin women was due in part to genotype enrichment by a CYP11B2 (-344T/C) variant. CONCLUSIONS AND GENERAL SIGNIFICANCE: Since the optimized PFRM consistently outperformed BCRAT in all Caucasian study populations, it represents an improved personalized risk assessment tool. The finding of higher Marin County risk linked to a CYP11B2 aldosterone synthase SNP associated with essential hypertension offers a new genetic clue to sporadic breast cancer predisposition.

Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence population: a pilot study.

BACKGROUND: Marin County, CA has very high incidence of breast cancer. Traditional risk factors, such as those included in the Gail model, do not effectively stratify breast cancer in this population. This retrospective case-control pilot study evaluates DNA from volunteers from a previous Marin County breast cancer epidemiology study. A polyfactorial risk model (OncoVue; InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5 clinical risk factors was used to stratify risk in Marin County women. STUDY DESIGN: DNA genotyping was performed on 164 Caucasian women diagnosed with primary breast cancer in Marin County from 1997 to 1999 and 174 age- and ethnicity-matched control subjects. Individual lifetime risks were determined using the polyfactorial risk model and genotype frequencies in women at elevated risk were compared with the overall genotypes. RESULTS: The vitamin D receptor VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes were also present, but in lower frequencies. CONCLUSIONS: The high frequency of the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk for breast cancer by the polyfactorial risk model might be related to the high incidence rates of breast cancer in Marin County, CA. Vitamin D supplementation could modify risk of breast cancer in this population.

Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer.

Dietary indoles, present in Brassica plants such as cabbage, broccoli, and Brussels sprouts, have been shown to provide potential protection against hormone-dependent cancers. 3,3'-Diindolylmethane (DIM) is under study as one of the main protective indole metabolites. Postmenopausal women aged 50-70 yr from Marin County, California, with a history of early-stage breast cancer, were screened for interest and eligibility in this pilot study on the effect of absorbable DIM (BioResponse-DIM) supplements on urinary hormone metabolites. The treatment group received daily DIM (108 mg DIM/day) supplements for 30 days, and the control group received a placebo capsule daily for 30 days. Urinary metabolite analysis included 2-hydroxyestrone (2-OHE1), 16-alpha hydroxyestrone (16alpha-OHE1), DIM, estrone (El), estradiol(E2), estriol (E3), 6beta-hydroxycortisol (6beta-OHC), and cortisol in the first morning urine sample before intervention and 31 days after intervention. Nineteen women completed the study,for a total of 10 in the treatment group and 9 in the placebo group. DIM-treated subjects, relative to placebo, showed a significant increase in levels of2-OHE1 (P=0. 020), DIM (P =0. 045), and cortisol (P = 0.039), and a nonsignificant increase of 47% in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to 2.14 (P=0.059). In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites.