Variants in Vitamin D-related Genes and Prostate Cancer Risk in Black Men.

BACKGROUND: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. However, Black men have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine six critical genes in the vitamin D pathway and prostate cancer risk in Black men. METHODS: We assessed a total of 69 candidate variants in six genes ( GC, CYP27A1, CYP27B1, CYP24A1, VDR , and RXRA ) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.000724 was used to account for the 69 variants tested. RESULTS: None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Four variants tested P<0.05 in Black men, including two in RXRA (rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055). CONCLUSION: We observed suggestive non-significant associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

"There is no expiration date": a qualitative analysis using the Social Cognitive Theory to identify factors influencing physical activity among adults living with advanced cancer.

PURPOSE: To identify cognitive, behavioral, environmental, and other factors that influence physical activity in adults with advanced cancer using qualitative, semi-structured interviews. METHODS: Eighteen semi-structured interviews were conducted with adults living with stage IV breast, prostate, or colorectal cancer; or multiple myeloma recruited from the University of Wisconsin Carbone Cancer Center. We used the Social Cognitive Theory to design the interview guide and a reflexive thematic approach for analysis. RESULTS: Participants were 62 years old on average and currently receiving treatment. Despite reporting numerous barriers to physical activity, most participants discussed engaging in some physical activity. Participants reported difficulties coping with changes in physical functioning especially due to fatigue, weakness, neuropathy, and pain. While cold weather was seen as a deterrent for activity, access to sidewalks was a commonly reported feature of neighborhood conduciveness for physical activity. Regardless of current activity levels, adults with advanced cancer were interested in engaging in activities to meet their goals of gaining strength and maintaining independence. Having a conversation with a provider from their cancer care team about physical activity was seen as encouraging for pursuing some activity. CONCLUSIONS: Adults living with advanced cancer are interested in pursuing activity to gain strength and maintain independence despite reported barriers to physical activity. To ensure patients are encouraged to be active, accessible resources, targeted referrals, and interventions designed to address their goals are critical next steps. RELEVANCE: Integrating conversations about physical activity into oncology care for adults living with advanced cancer is an important next step to encourage patients to remain active and help them improve strength and maintain quality of life and independence.

Does religious involvement affect mortality in low-income Americans? A prospective cohort study.

OBJECTIVE: This study aimed to evaluate the impacts of various forms of religious involvement, beyond individual socioeconomic status, lifestyle factors, emotional well-being and social support, on all-cause and cause-specific mortality in socioeconomic disadvantaged neighbourhoods. DESIGN: This is a prospective cohort study conducted from 2002 through 2015. SETTINGS: This study included underserved populations in the Southeastern USA. PARTICIPANTS: A total of nearly 85 000 participants, primarily low-income American adults, were enrolled. Eligible participants were aged 40-79 years at enrolment, spoke English and were not under treatment for cancer within the prior year. RESULTS: We found that those who attended religious service attendance >1/week had 8% reduction in all-cause death and 15% reduction in cancer death relative to those who never attended. This association was substantially attenuated by depression score, social support, and socioeconomic and lifestyle covariates, and further attenuated by other forms of religious involvement. This association with all-cause mortality was found being stronger among those with higher socioeconomic status or healthier lifestyle behaviours. CONCLUSION: Our results indicate that the association between religious services attendance >1/week and lower mortality was moderate but robust, and could be attenuated and modified by socioeconomic or lifestyle factors in this large prospective cohort study of underserved populations in the Southeastern USA.

Diabetes, obesity, and subsequent risk of postmenopausal breast cancer among white and black women in the Southern Community Cohort Study.

PURPOSE: Meta-analyses have reported a small but positive association between diabetes and postmenopausal breast cancer risk, with summary relative risks of approximately 1.15. We analyzed data from the Southern Community Cohort Study (SCCS) following an underserved population with high diabetes prevalence to prospectively examine whether diabetes was associated with subsequent postmenopausal breast cancer risk and whether obesity modified this effect. METHODS: Women with incident breast cancer were identified through linkage with state cancer registries and the National Death Index (213 white, 418 black cases). Person-years were calculated from date of entry into the SCCS until the earliest of date of breast cancer diagnosis, date of death, or date of last follow-up (8,277 white, 16,458 black noncases). Data on diabetes diagnosis were obtained through baseline and follow-up surveys. Cox regression was applied to examine the association between diabetes and postmenopausal breast cancer risk. RESULTS: After adjustment for confounding, there was no association between self-reported diabetes and postmenopausal breast cancer risk among white (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.75-1.40) or black (HR 1.00, 95% CI 0.81-1.22) women. Nor was there evidence that obesity modified the effect of diabetes on postmenopausal breast cancer in women of either race. CONCLUSIONS: We found no evidence of the hypothesized increased risk of breast cancer among women with diabetes. The breast cancer risks among those with diabetes in this population suggest that the association between these two illnesses is complex.

Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans.

Background: Previous studies rarely evaluated the associations between vitamin D-binding protein and free vitamin D with colorectal cancer risk. We assessed these biomarkers and total 25-hydroxyvitamin D in relation to colorectal cancer risk in a sample of African Americans.Methods: Cases comprised 224 African American participants of the Southern Community Cohort Study diagnosed with incident colorectal cancer. Controls (N = 440) were selected through incidence density sampling and matched to cases on age, sex, and race. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between biomarker levels and colorectal cancer risk.Results: Vitamin D was inversely associated with colorectal cancer risk where the OR per-SD increase in total and free 25-hydroxyvitamin D were 0.82 (95% CI, 0.66-1.02) and 0.82 (95% CI, 0.66-1.01), respectively. Associations were most apparent among cases diagnosed >3 years after blood draw: ORs for the highest tertile versus the lowest were 0.69 (95% CI, 0.21-0.93) for total 25-hydroxyvitamin D and 0.71 (95% CI, 0.53-0.97) for free 25-hydroxyvitamin D. Inverse associations were seen in strata defined by sex, BMI, and anatomic site, although not all findings were statistically significant. Vitamin D-binding protein was not associated with colorectal cancer risk.Conclusions: Our findings suggest that total and free 25-hydroxyvitamin D may be inversely associated with colorectal cancer risk among African Americans.Impact: These findings highlight a potential role for vitamin D in colorectal cancer prevention in African Americans. Cancer Epidemiol Biomarkers Prev; 26(8); 1242-7. ©2017 AACR.

Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study.

OBJECTIVE: Genomewide association studies have consistently found variants in fibroblast growth factor receptor 2 (FGFR2) to be associated with breast cancer. Recent reports suggest that postmenopausal hormone therapy (HT) use may modify the association between single nucleotide polymorphisms (SNPs) in FGFR2 and breast cancer risk. We assessed the hypothesis that the association between rs1219648 (FGFR2) SNP and breast cancer risk is modified by postmenopausal HT use in a population-based case-control study. METHODS: We evaluated rs1219648 SNP for an association with breast cancer risk using data obtained from 869 postmenopausal breast cancer cases diagnosed between 1995 and 2000 and from 808 postmenopausal community controls who participated in a study conducted in three US states. Detailed postmenopausal HT information was collected through a structured telephone interview, and DNA samples were collected by mail using an established mouthwash protocol. Odds ratios and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for age and state of residence. RESULTS: We observed a significant association between rs1219648 and breast cancer risk (per-allele odds ratio, 1.22; 95% CI, 1.06-1.41; P = 0.007), which did not vary significantly by ever use of estrogen plus progestogen therapy (interaction P = 0.48). There was stronger evidence of an interaction between ever use of estrogen-only HT and increasing number of rs1219648 risk alleles to increase breast cancer risk (interaction P = 0.08). CONCLUSIONS: Our results are consistent with a risk association with FGFR2 but provide limited support for interaction with HT use. The study raises the possibility that the FGFR2 rs1219648 variant is more strongly associated with risk in estrogen-only hormone users, although this observation needs to be examined in larger studies.