Loading...
 
Toggle Health Problems and D

Hypothesis: Blacks get more cancer than whites due to lower levels of vitamin D – June 2012

Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and White Americans

Dermato Endocinology Volume 4, Issue 2 April/May/June 2012
Authors: William B. Grant and Alan N. Peiris


Considerable disparities in cancer survival rates exist between African Americans (Aas) and white Americans (Was). Various factors such as differences in socioeconomic status (SES), cancer stage at time of diagnosis, and treatment—which this analysis considers primary explanatory factors—have accounted for many of these differences. An additional factor not usually considered is vitamin D. Previous studies have inversely correlated higher solar UV-B (UVB) doses and serum 25-hydroxyvitamin D (25(OH)D) concentrations with incidence and/or mortality rates for about 20 types of cancer and improved survival rates for eight types of cancer. Because of darker skin pigmentation, Aas have 40% lower serum 25(OH)D concentrations than Was. This study reviews the literature on disparities in cancer survival between Aas and Was. The journal literature indicates that there are disparities for 13 types of cancer after consideration of SES, stage at diagnosis and treatment: bladder, breast, colon, endometrial, lung, ovarian, pancreatic, prostate, rectal, testicular, and vaginal cancer; Hodgkin’s lymphoma; and melanoma. Solar UVB doses and/or serum 25(OH)D concentrations have been reported inversely correlated with incidence and/or mortality rates for all of these cancers. This finding suggests that future studies should consider serum 25(OH)D concentrations in addressing cancer survival disparities through both measurements of serum 25(OH)D concentrations and increasing serum 25(OH)D concentrations of those diagnosed with cancer, leading to improved survival rates and reduced disparities.

CLICK HERE for online version

- - - - - - -

Clipped from Newswise

The journal literature indicates that there are disparities for 13 types of cancer after consideration of socioeconomic status, stage at diagnosis and treatment: bladder, breast, colon, endometrial, lung, ovarian, pancreatic, prostate, rectal, testicular, and vaginal cancer; Hodgkin’s lymphoma; and melanoma. Solar UVB doses and/or vitamin D have been reported inversely correlated with incidence and/or mortality rates for all of these cancers.The unexplained portion is generally between zero and 30%, with an average near 15%. A disparity of 25% is expected from a consideration of serum vitamin D concentrations for African-Americans (16 ng/ml or 40 nmol/l) and white-Americans (25 ng/ml or 63 nmol/l) based on relations between serum vitamin D concentrations and incidence rates for breast and colorectal cancer. However, the effect for other cancers may be lower than for breast and colorectal cancer.

African-Americans have vitamin D concentrations lower than white-Americans since their darker skin pigmentation reduces the penetration of UVB, thus, reduces the production of vitamin D. Dark skin is an advantage in Africa, where solar UVB doses are quite high, but a disadvantage in the United States, where it isn’t.

According to William B. Grant, Ph.D., a coauthor of the paper and director of Sunlight, Nutrition and Health Research Center, “Raising vitamin D concentrations to 40 ng/ml by taking 1000-4000 IU/d vitamin D3 supplements is the easiest thing African-Americans can do to reduce the heavy burden of cancer they experience. In addition to reducing the risk of cancer, vitamin D would also reduce the risk of cardiovascular disease, diabetes mellitus, respiratory infections and many other chronic and infectious diseases.”

According to Alan N. Peiris, M.D,PhD. FRCP(Lon), a co-author and Chief of Endocrinology at Mountain Home VAMC and East Tennessee State University, monitoring of vitamin D status is often inadequate. Given the wide range of dose responses to vitamin D replacement, it is prudent to monitor levels of 25(OH)D following initiation of dosing. This enables maintaining desired levels over the long term which may facilitate accrual of maximal benefit.
- - - - - - - - - -

Background

Considerable disparities in cancer survival rates exist between African Americans (AAs) and white Americans (WAs). Various factors such as socioeconomic status (SES),1 cancer stage at time of diagnosis, and treatment2 have accounted for many of these disparities. Educational attainment is often used as a proxy for SES.3 Other factors include insurance status,4 social determinants in general,5,6 and genetics.7,8 However, even when analyses of cancer survival data include all known or suspected factors affecting survival, AAs still tend to have a lower survival rate than that of WAs, possibly because of unmodeled factors such as biological differences, and perhaps as a consequence of educational level and access to health care as several authors have noted.9-12

Discussions of cancer survival disparities generally overlook the role of vitamin D. For 2001–2004, AAs older than 60 y had a population mean serum 25-hydroxyvitamin D [25(OH)D] concentration of 17 ng/ml compared with 25 ng/ml for WAs.13 Prevalence of hypovitaminosis D [(25(OH)D < 15 ng/ml] in the South was 45% among blacks and 11% among whites.14 In patients participating in a randomized controlled trial of chemotherapy, serum 25(OH)D concentrations were lower in black patients than in white patients and patients of other race (median, 10.7 vs 21.1 vs 19.3 ng/ml, respectively; p < 0.001), as well as in females compared with males (median, 18.3 vs 21.7 ng/ml, respectively; p = 0.0005).15 Solar UV-B (UVB) irradiance is the primary source of vitamin D for most Americans, accounting for 80–90% of vitamin D.16 AAs, with darker skin, are less efficient at producing vitamin D from UVB irradiance.17 In addition, AAs are less likely to have as much vitamin D from oral intake.18

A large body of literature supports a beneficial effect of vitamin D in reducing the risk of cancer incidence and mortality rates. The UVB–vitamin D–cancer hypothesis was proposed in 1980.19 Many ecological studies20-24 have supported this hypothesis, as have observational studies of breast and colorectal cancer.25,26 Two ecological studies found stronger inverse correlations between solar UVB doses and cancer mortality rates than incidence rates.23,24 Several reviews of the UVB-vitamin D-cancer hypothesis have also been published.27,28 Two randomized controlled trials found positive effects.29,30

The dose–response relation for vitamin D has been derived from observational studies for breast and colorectal cancer.25 For the differences in population mean serum 25(OH)D concentrations for 2001–2004,13 the dose–response relations for breast and colorectal cancer indicate a 20–25% increase in incidence rate. The values for cancer incidence are not necessarily the same for cancer survival, but they do suggest the magnitude of the effect. This vitamin D-cancer dose–response relation might underestimate the effect of lower serum 25(OH)D concentrations for AAs since 20% of the black population is older than 60 y, in contrast to only 6% of whites; also, the risk of cancer increases more rapidly for changes of serum 25(OH)D concentration at lower concentrations.

A recent paper addressed vitamin D’s role in explaining some of the cancer survival disparities. Data from the Third National Health and Nutrition Examination Survey (NHANES III) were used to investigate the role of racial disparity from colorectal cancer; adding vitamin D deficiency to the model attenuated the mortality risk associated with being black by a statistically significant 40%.31 Grant and Peiris32 investigated vitamin D’s role in explaining disease disparities between AAs and WAs in general.

This paper surveys the literature on cancer disparities for AAs and WAs as well as the literature on epidemiological studies on vitamin D and cancer to see whether differences in serum 25(OH)D concentrations might explain many of the otherwise-unaccounted-for residual disparities.

Results

Table 1 presents the findings regarding cancer survival with respect to serum 25(OH)D concentrations at the time of diagnosis. Significant inverse correlations between 25(OH)D and cancer survival were found for all-cancer, breast, colon, colorectal, lung, prostate cancer, chronic lymphocytic leukemia/chronic lyphocytic lymphoma, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma. Studies also reported no significant correlation between serum 25(OH)D and survival for bladder, lung, and ovarian cancer.

Table 1 presents the findings regarding cancer survival with respect to serum 25(OH)D concentrations at the time of diagnosis. Significant inverse correlations between 25(OH)D and cancer survival were found for all-cancer, breast, colon, colorectal, lung, prostate cancer, chronic lymphocytic leukemia/chronic lyphocytic lymphoma, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma. Studies also reported no significant correlation between serum 25(OH)D and survival for bladder, lung, and ovarian cancer.

Table 1. Evidence that vitamin D increases cancer-specific and all-cause survival rates
Cancer typeConditionsRecurrence, vitamin D deficiency
[HR (95% confidence interval)]
Survival,
vitamin D adequacy
[HR or RR (95% confidence interval)]
Survival, vitamin D deficiency
[HR or RR (95% confidence interval)]
Reference
AllVitamin D supplementation in intention-to-treatHR = 0.85 (0.68–1.06) (mortality)33
AllNorway, 9.3-y follow up, high vs. low quartileHR 0.36 (0.27–0.51) p < 0.01 CS34
BladderThree years of follow up, summer vs. winter diagnosisRR = 1.0 (0.97–1.07) AC35
BreastThree years of follow up, fall vs. winter diagnosis0.70 (0.65–0.75)36
BreastThree years of follow up, summer vs. winter diagnosisRR = 0.75 (0.72–0.79) AC37
BreastWomen in Canada, 11.6 y follow-up,HR = 1.71 (1.02–2.86) for distant recurrence;HR = 1.60
(0.96–2.64) AC
38
Breast, luminal40-mo follow upHR = 3.97 (1.77–8.91, p = 0.001)39
BreastContinuous per 10 nmol/L decrement; distant disease, overall mortalityHR = 1.14 (1.05–1.24) p = 0.006HR = 1.08
(1.00–1.17) p = 0.07
40
BreastNorway, 9.3-y follow up, high vs. low quartileHR = 0.42 (0.21–0.82), p = 0.01 CS34
Chronic lymphocytic leukemia, chronic lymphocytic lymphomaMean follow-up 36 mo (1–86 mo)HR = 1.47 (1.11–1.96)
p = 0.008
HR = 1.47
(0.97–2.23)
p = 0.07 AC
41
ColonThree years of follow up, fall vs. winter diagnosis0.71 (0.66–0.77) men; 0.68 (0.64–0.72) women35
ColonThree-year follow up, summer vs. winter diagnosis, Midwest region, NorwayMen < 65 y, RR = 0.70 (0.5–0.83) AC
Women < 65 y, RR = 0.77 (0.66–0.90) AC
42
ColonNorway, 9.3-y follow up, high vs. low quartileHR = 0.20 (0.01–1.10), p = 0.16 CS34
ColorectalMean follow-up time 116 mo, used predicted 25(OH)D concentrationHR = 0.50 (0.26–0.95) CS43
Hodgkin’s lymphoma18 and 36 mo follow up, based on season, autumn vs. winter diagnosis, NorwayRR = 0.78 (0.62–0.99) p = 0.04
AC
44
LungThree years of follow up, summer vs. winter diagnosisRR = 1.00 (0.98–1.02) AC45
Lung> 27.7 ng/ml vs. < 12.6 ng/ml1.08 (0.75–1.57) p = 0.76
AC
46
LungNorway, 9.3-y follow up, high vs. low quartile0.18 (0.11–0.29), p < 0.001, CS34
LymphomaNorway, 9.3-y follow up, high vs. low quartileHR = 0.39 (0.18–0.83), p = 0.01 CS34
NHL, diffuse large B-cell lymphoma5-y follow upHR = 1.41 (0.98–2.04)HR, 1.99 (1.27–3.13), AC47
NHL, T-cell lymphoma5-y follow upHR = 1.94 (1.04–3.61)HR, 2.38 (1.04–5.41)47
OvarianThree years of follow up, summer vs. winter diagnosisRR = 1.00 (0.98–1.07) AC35
ProstateThree years of follow up, fall vs. winter diagnosis0.70 (0.66–0.74)36
ProstateThree years of follow up, summer vs. winter diagnosisRR = 0.76 (0.73–0.79) AC48
ProstateThe mean age (standard deviation, SD) at blood draw of
participants in the analysis was 63.7 (7.8) years in HPFS and 59.2
(7.6) years in PHS. The mean age (SD) at cancer diagnosis was
69.5 (7.4) years in HPFS and 67.8 (6.5) years in PHS.
HR: 1.59 (1.06–2.39) P(trend) = 0.006
(lowest vs. highest quartile)
49

AC, all cause; CS, cancer specific; HR, hazard ratio; NHL, non-Hodgkin’s lymphoma; RR, relative risk

Table 2 presents the multifactor-adjusted hazard ratios for survival for AAs vs. WAs for cancer-specific survival. Inclusion of SES, stage at diagnosis, and treatment in the analyses is indicated. Table 2 lists nearly all the relevant papers. The results for cancer-specific survival rates are a stronger indication of the effects of vitamin D than are all-cause survival rates because some of the all-cause deaths could be due to non-vitamin D–related diseases or to factors such as smoking. Statistically significant disparities emerged for cancer-specific survival rates for 13 types of cancer: bladder, breast, colon, endometrial, lung (non-small cell, stage III, IV), ovarian (advanced), pancreatic, prostate, rectal, testicular, vaginal cancer, Hodgkin lymphoma, stage II, and melanoma. Our analysis also found statistically significant disparities for cancer-specific survival rates for two types of cancer, endometrial and ovarian cancer,. There were no statistically significant findings for gastric adenocarcinoma, or head and neck, and oral cancer, and leukemia.

Table 2. Cancer-specific mortality rate disparities for AAs vs. WAs not explained by known factors for 25 types of cancer. Studies reported that AAs have significantly increased risk for 13 types of cancer after consideration of SES, cancer stage at time of diagnosis, and treatment
CancerSESCancer stage at diagnosisTreatmentRelative Risk (95% CI),
AAs vs. WAs
Ref.
BladderY1.68 (1.28–2.21)50
Bladder, males, 1- to 2-y follow-upYY1.26 (1.15–1.37)12
Bladder, males, 3- to 4-y follow-upYY1.16 (0.96–1.41)12
Bladder, females, 1- to 2-y follow-upYY1.20 (1.09–1.32)12
Bladder, males, 3- to 4-y follow-upYY1.55 (1.21–1.98)12
BladderYYY1.73 (1.23–2.43)51
BladderYYY1.29 (1.24–1.36)52
Breast, meta-analysisY1.23 (1.05–1.20)53
Breast, meta-analysisY1.22 (1.10–1.37)50
Breast—premenopausalYYY1.41 (1.09–1.84)10
Breast—postmenopausalYYY1.39 (1.17–1.66)10
Breast, Stage 1, 2YYY1.55 (1.13–2.13)54
Breast (metastasis)YYY1.20 (0.96–1.50)55
BreastYYY2.41 (1.21–4.79)56
CervicalNo difference57
Colon, meta-analysisYY1.13 (1.01–1.28)58
ColonY1.19 (1.14–1.25)59
ColonYY1.15 (1.10–1.20)59
ColonYYY1.08 (1.03–1.13)59
Colon, early stageYYY0.99 (0.67–1.45)10
Colorectal1.33 (1.30–1.36)60
ColorectalYYY1.31 (1.21–1.42)61
EndometrialY2.08 (1.34–3.21)50
EndometrialYYY1.5162
EndometrialY1.60 (1.51–1.69)63
EsophagealYYY1.0264
Gastric adenocarcinomaYY1.03 (0.95–1.12)65
Gastric adenocarcinomaY1.18 (0.94–1.49)66
Head and neckYYY1.06 (0.50–2.25)67
Hodgkin lymphoma, stage IYY1.22 (0.81–1.85)68
Hodgkin lymphoma, stage IIYY1.35 (1.12–1.62)68
Leukemia, acute myelogenousYYY1.05 (0.83–1.33)10
Lung cancer, small cell, limited1.11 (0.77–1.60)10
Lung cancer, NSC, advanced0.89 (0.75–1.05)10
Lung cancer, NSC, stage I, IIYY0.97 (0.85–1.10)69
Lung cancer, NSC, stage III, IVYY1.24 (1.01–1.53)69
MelanomaYYYHR, 1.60 (1.17 –2.18)9
Multiple myelomaYYY0.85 (0.70–1.03)10
Nasopharyngeal1.00 (0.82, 1.24)70
Non-Hodgkin’s lymphoma (NHL)YYY1.07 (0.92–1.25)71
NHL, advancedYYY1.17 (0.94–1.45)10
OralYYY1.1 (0.9–1.4)72
Ovarian, advancedYYY1.41 (1.03–2.11)10
Ovarian, stage 3YY1.06 (0.61–1.79).73
Ovarian, 1973–2007YY1.14 (1.07–1.21)74
Ovarian, 2003–2007YY1.29 (1.12–1.49)74
Pancreatic0.93 (0.83–1.04)75
Pancreatic—adenocarcinomaYYY1.00 (0.94–1.06)76
Pancreatic1.42 (1.28–1.58)11
Prostate (meta-analysis)YYY1.13 (1.00–1.27)77
Prostate—55–84 yYApprox 278
Prostate, advancedYYY1.19 (1.05–1.35)10
Prostate, meta-analysisYYY1.15 (0.95–1.41)79
RectalY1.27 (1.17–1.38)58
RectalYY1.19 (1.09–1.29)58
RectalYYY1.11 (1.02–1.20)58
RenalNo difference80
TesticularYYY2.1281
Thyroid (5-y survival, blacks vs whites)96.5% vs 97.4%,
p = 0.006
82
VaginalYY1.2 (1.1–1.4)83

NSC, non-small cell; SES, socioeconomic status

Discussion

This review offers evidence to explain cancer survival differences between AAs and WAs. AAs’ lower serum 25(OH)D concentrations (mainly from reduced vitamin D photoproduction owing to darker pigmentation) may account for much of the unexplained survival disparity after consideration of such factors as SES, stage at diagnosis, and treatment. All cancers for which a disparity in cancer-specific survival was reported also have evidence for a beneficial role of vitamin D, as do most of those for which we found disparities for all-cause survival.

One reason ecological studies are strong include that vitamin D plays an important role in reducing risk of cancer initiation and angiogenesis around tumors and metastases.84,85 Since cancer can take years to decades to reach the stage of detection or death, continued high serum 25(OH)D concentrations over much of the lifetime is required for greatest risk reduction. Most recent ecological studies include various cancer risk–modifying factors in the analysis.20-24 Also, ecological studies include many cases, thereby reducing the uncertainty of the values. Among 45-y-old British citizens, casual solar UVB irradiance in summer increased serum 25(OH)D concentrations by about 15 ng/ml,86 enough to have an important impact on cancer risk.25,29 For example, breast cancer incidence rates are highest in spring and fall.87 The reasons for the seasonal variations given were increased production of vitamin D in summer and melatonin in winter. Breast cancer has several subtypes, and rate of progression can vary widely, with some being very rapid. For slower growing cancers, serum 25(OH)D concentrations in summer may be sufficient to retard or reverse the growth.

Once cancer reaches the point where it can be diagnosed, vitamin D improves cancer-specific survival by several mechanisms, including antiangiogenesis and antimetastases.84,85 The disparities for hematopoietic cancers may be weak or nonexistent because angiogenesis and metastases are less important for blood cell–related tumors than for solid tumors. Higher serum 25(OH)D concentrations also affect all-cause mortality rates88 since vitamin D protects against several major life-threatening conditions for the elderly,89-91 including diabetes and cardiovascular disease, influenza and pneumonia, and falls and fractures.

Secondary hyperparathyroidism due to osteoblastic metastases and hungry bone syndrome has been described with advanced prostate and breast cancer, it is likely that a vitamin D replete state may minimize such occurrences.92 Bisphosphonates are commonly used in oncology. Pamidronate administration improved the secondary hyperparathyroidism due to “Bone Hunger Syndrome” in a patient with osteoblastic metastases from prostate cancer. Coleman93 suggest that bisphosphonates may prevent metastases and reduce the risk of disease recurrence. Based on animal data,94 a vitamin D replete state may be helpful in reducing bisphosphonate induced osteonecrosis of the jaw.

Factors other than SES, stage at diagnosis, treatment, and vitamin D status might also explain the cancer survival disparities. For example, the lack of survival disparities for lung cancer may be due to a stronger effect from smoking than from vitamin D. Smoking cessation improves lung cancer survival rates associated with early-stage lung cancer.95

Obesity is significantly correlated with cancer risk for nearly all types of cancer listed in Tables 1 and 2.96,97 AAs tend to have higher body mass index than WAs. One reason is that obesity is linked to poverty in the United States because of energy-dense but nutrient-poor foods are cheaper due to subsidies.98 A second reason is that AAs have about twice the prevalence of apolipoprotein E ?4 (ApoE4) than WAs.99 ApoE4 increases production of cholesterol in the liver and of insulin in the pancreas to store excess food as fat for those with sporadic food supplies, such as hunter–gatherers. Interestingly, overweight and obesity rates for white and black men differ little, whereas AA women are much heavier than WA women (http://www.cdc.gov/NCHS/data/hestat/obesity_adult_07_08/obesity_adult_07_08.pdf). Thus, obesity does not seem to be a likely explanation for cancer disparities among men but could be for women. On the other hand, serum 25(OH)D concentrations are inversely correlated with body mass index, which has implications for cancer risk.100 Interestingly, for pancreatic cancer incidence, higher body mass index was significantly associated with risk for AA and WA men and WA women but with only insignificantly reduced risk for AA women.11

Cancer survival studies with respect to serum 25(OH)D concentrations at time of diagnosis offer strong evidence for a beneficial effect of vitamin D. All cancers with a beneficial effect of vitamin D on survival have been found inversely correlated with solar UVB doses, with the possible exception of chronic lymphocytic leukemia.41 There are also studies from Norway indicating improved survival for those diagnosed with breast, colon, prostate cancer and Hodgkin’s lymphoma in summer compared with winter.35

The UVB–vitamin D–cancer hypothesis receives its strongest support from ecological studies.19-24,27,28 Observational studies also provide good support if the various studies are examined carefully and a good reason is found for why many observational studies have not found a beneficial effect of vitamin D in reducing the risk of cancer. Nested case–control studies have a reduced strength since only a single serum 25(OH)D concentration measurement or oral intake assessment is made at time of enrollment, with follow-up periods lasting between 3 and 28 y.101 As the follow-up time increases beyond about 3–7 y, the single measurement is less meaningful.101,102 Case–control studies, on the other hand, use serum 25(OH)D concentration or vitamin D oral intake values at the time of diagnosis. A review of observational studies of breast and colorectal cancer incidence with respect to serum 25(OH)D concentration found statistically significant inverse correlations for breast cancer out to 3 y and for colorectal cancer out to 12 y of follow-up.101 Thus, the recently reported results from the Vitamin D Pooling Project study of rarer cancer types (endometrial, esophageal, gastric, ovarian, pancreatic, and renal cancer and non-Hodgkin’s lymphoma)103 probably failed to find an inverse correlation between incidence of these cancers and prediagnostic serum 25(OH)D concentrations because the mean follow-up period was 6.63 y and because there were so few cases that the 95% confidence intervals were about 50%. The correlation between serum 25(OH)D concentrations measured at different times decreases with time, dropping to a regression coefficient of 0.40 after 14 y.104

Several ways exist to test the UVB–vitamin D–cancer hypothesis as an additional contributing factor for cancer survival disparities. One would be to measure serum 25(OH)D concentrations of newly diagnosed cancer patients and at several intervals during the course of the cancer. Another would be to supplement newly diagnosed cancer patients with sufficient vitamin D to bring serum 25(OH)D concentrations up to 40–80 ng/ml and compare results for those not supplemented, perhaps from previous patients in the same practice. A recent publication described the rationale for vitamin D supplementation,105 which is being done in some cancer treatment centers.106,107 Increasing serum 25(OH)D concentrations would also reduce the risk of severe sepsis associated with cancer surgery108 as well as many other comorbid diseases.89-91

Study Caveats

We acknowledge that while it appears very likely that vitamin D is an important and often ignored factor in the biology of cancer, the issue of cancer etiology is complex and is clearly multifactorial. Moreover, outcomes studies may have skewed results since AA men are less likely to participate in cancer screening trials.109 Black women may be less physically active.110 An inverse relationship between physical activity and breast cancer in AA women has been reported.111 Some of the adverse cancer outcomes may relate to less than optimal care. Esnaola et al.112 reported that AA patients are less likely to receive resection in non-metastatic rectal cancer. Rolnick113 demonstrated that AA colorectal cancer survivors are less likely to receive post-treatment colorectal surveillance. Similar findings have been found in prostate cancer.114 These may not necessarily reflect racism in that physicians may make recommendations based on a patient’s access to health care, presence of insurance, etc.115 In addition, poor health literacy in AA women may also impact access to available health care strategies.116

Cultural differences may also play a role with cultural insensitivity among providers compounding the issue. Margolis117 demonstrated significant racial differences in belief prior to lung cancer surgery. Some of these differences result in refusal of surgery on the part of AA patients. AAs have less trust in their health providers and may not accept physicians’ assertions regarding treatment.117 Spiritually based health interventions may be more effective in AAs.118 Van Ness119 indicates that lack of religiousness maybe associated with poor cancer survival in AA women. Church attendance may be associated with greater emotional and social support, which is linked to better outcomes in breast cancer.

We must also consider the possibility that apart from direct cellular benefits of vitamin D on cancer that vitamin D deficiency has indirect effects which are hard to quantify but may have a significant impact on cancer outcomes. Vitamin D deficiency is also associated with a higher prevalence of depression and neurocognitive symptoms, which makes patients intrinsically less likely to seek medical attention . Treating vitamin D deficiency may ameliorate symptoms of depression.120

Some risk factors such as diet can be modified and increased consumption of vegetables may decrease the risk of breast cancer in AAs, possibly by altering estrogen/progesterone receptor status.121 Fortunately, it does appear that tumors are not intrinsically more aggressive in AAs.122 In Veterans with equal access to health care, lung and colon cancer are not necessarily more aggressive diseases in AAs.123 Dignam reported that black women, diagnosed at comparable disease stage as white women and treated appropriately, tend to experience similar breast cancer prognoses and survival.124

Some of the residual disparity for prostate cancer may be due to the higher prevalence of the ApoE4 allele among AAs than WAs,99 which is related to increased cholesterol production. Cholesterol is an important risk factor for high-grade prostate cancer.125 Increased low-density lipoprotein concentrations increased the risk of prostate cancer for AAs but not WAs.126

Conclusion

Lower serum 25(OH)D concentrations among AAs than WAs may explain many of the cancer survival disparities after consideration of SES, stage at time of diagnosis, and treatment. More research is required to confirm this hypothesis. If substantially correct, programs to increase serum 25(OH)D concentrations among AAs could reduce the cancer disparities. This approach would work not only for those of the ages where cancer is more likely but also for those younger. Vitamin D can reduce the risk of cancer at the initiation stage and in the advanced stages, as well as raising serum 25(OH)D concentrations to over 40 ng/ml shortly after cancer diagnosis. Given the biologic plausibility, the currently available evidence of beneficence, and the lack of harm with moderate Vitamin D replacement, we recommend Oncologists consider a more proactive stance on this issue pending additional studies.

Materials and Methods

Being a review, this analysis summarizes papers in the journal literature. Papers cited in this study came from the National Library of Medicine’s PubMed database (http://www.pubmed.gov). As of December 28, 2011, a search for cancer disparity papers (search terms “cancer disparities survival, African-American”) identified 457 articles. We reviewed the titles and abstracts of many of these. We examined in more detail those reporting hazard ratios for AAs vs. WAs for survival. The tables in this review do not include the component papers of meta-analyses cited. Thus, the papers listed in the tables are representative rather than exhaustive. We inspected the results in the papers, preferring those with disparities in survival that included all three factors—SES, stage at diagnosis, and treatment, in addition to race—over those including fewer or none of these factors. We examined the papers to see whether survival was cancer-specific or all-cause.

In addition, papers reporting cancer survival with respect to serum 25(OH)D concentration were also sought.

Disclosure of Potential Conflicts of Interest

W.B.G. receives funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).

Disclaimer

A.N.P. acknowledges use of resources at Mountain Home VAMC. The services of the Library staff at Mountain Home VA and affiliated sites are gratefully acknowledged. This paper does not represent the position of the Department of Veterans Affairs or the US Government.

References

1. Byers TE, Wolf HJ, Bauer KR, Bolick-Aldrich S, Chen VW, Finch JL, et al. The impact of socioeconomic status on survival after cancer in the United States : findings from the National Program of Cancer Registries Patterns of Care Study. Cancer 2008; 113:582-91; PMID: 18613122; DOI: 10.1002/cncr.23567.

2. Brawley OW. Is race really a negative prognostic factor for cancer?. J Natl Cancer Inst 2009; 101:970-1; PMID: 19567421; DOI: 10.1093/jnci/djp185.

3. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61:212-36; PMID: 21685461; DOI: 10.3322/caac.20121.

4. DeSantis C, Jemal A, Ward E. Disparities in breast cancer prognostic factors by race, insurance status, and education. Cancer Causes Control 2010; 21:1445-50; PMID: 20506039; DOI: 10.1007/s10552-010-9572-z.

5. Gerend MA, Pai M. Social determinants of Black-White disparities in breast cancer mortality: a review. Cancer Epidemiol Biomarkers Prev 2008; 17:2913-23; PMID: 18990731; DOI: 10.1158/1055-9965.EPI-07-0633.

6. Satcher D. Include a social determinants of health approach to reduce health inequities. Public Health Rep 2010; 125:6-7; PMID: 20629251.

7. Brower V. Cancer disparities: disentangling the effects of race and genetics. J Natl Cancer Inst 2008; 100:1126-9; PMID: 18695126; DOI: 10.1093/jnci/djn302.

8. Dunn BK, Agurs-Collins T, Browne D, Lubet R, Johnson KA. Health disparities in breast cancer: biology meets socioeconomic status. Breast Cancer Res Treat 2010; 121:281-92; PMID: 20437200; DOI: 10.1007/s10549-010-0827-x.

9. Zell JA, Cinar P, Mobasher M, Ziogas A, Meyskens FL, Anton-Culver H. Survival for patients with invasive cutaneous melanoma among ethnic groups: the effects of socioeconomic status and treatment. J Clin Oncol 2008; 26:66-75; PMID: 18165642; DOI: 10.1200/JCO.2007.12.3604.

10. Albain KS, Unger JM, Crowley JJ, Coltman CA, Hershman DL. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 2009; 101:984-92; PMID: 19584328; DOI: 10.1093/jnci/djp175.

11. Arnold LD, Patel AV, Yan Y, Jacobs EJ, Thun MJ, Calle EE, et al. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity?. Cancer Epidemiol Biomarkers Prev 2009; 18:2397-405; PMID: 19723915; DOI: 10.1158/1055-9965.EPI-09-0080.

12. Scosyrev E, Noyes K, Feng C, Messing E. Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer 2009; 115:68-74; PMID: 19072984; DOI: 10.1002/cncr.23986.

13. Ginde AA, Liu MC, Camargo CA. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009; 169:626-32; PMID: 19307527; DOI: 10.1001/archinternmed.2008.604.

14. Egan KM, Signorello LB, Munro HM, Hargreaves MK, Hollis BW, Blot WJ. Vitamin D insufficiency among African-Americans in the southeastern United States: implications for cancer disparities (United States). Cancer Causes Control 2008; 19:527-35; PMID: 18219582; DOI: 10.1007/s10552-008-9115-z.

15. Ng K, Sargent DJ, Goldberg RM, Meyerhardt JA, Green EM, Pitot HC, et al. Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741. J Clin Oncol 2011; 29:1599-606; PMID: 21422438; DOI: 10.1200/JCO.2010.31.7255.

16. Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 2005; 10:94-111; PMID: 15989379.

17. Harris SS. Vitamin D and African Americans. J Nutr 2006; 136:1126-9; PMID: 16549493.

18. Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002; 76:187-92; PMID: 12081833.

19. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer?. Int J Epidemiol 1980; 9:227-31; PMID: 7440046; DOI: 10.1093/ije/9.3.227.

20. Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res 2006; 26:2687-99; PMID: 16886679.

21. Grant WB. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc 2006; 98:357-64; PMID: 16573299.

22. Grant WB. Ecological studies of the UVB-vitamin D-cancer hypothesis. Anticancer Res 2012; 32:223-36; PMID: 22213311.

23. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2002. BMC Cancer 2006; 6:264; PMID: 17096841; DOI: 10.1186/1471-2407-6-264.

24. Chen W, Clements M, Rahman B, Zhang S, Qiao Y, Armstrong BK. Relationship between cancer mortality/incidence and ambient ultraviolet B irradiance in China. Cancer Causes Control 2010; 21:1701-9; PMID: 20552265; DOI: 10.1007/s10552-010-9599-1.

25. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B 2010; 101:130-6; PMID: 20570169; DOI: 10.1016/j.jphotobiol.2010.04.008.

26. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 2011; 128:1414-24; PMID: 20473927; DOI: 10.1002/ijc.25439.

27. Grant WB. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer?: An examination using Hill’s criteria for causality. Dermatoendocrinol 2009; 1:17-24; PMID: 20046584; DOI: 10.4161/derm.1.1.7388.

28. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol 2009; 19:468-83; PMID: 19523595; DOI: 10.1016/j.annepidem.2009.03.021.

29. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85:1586-91; PMID: 17556697.

30. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94:1144-9; PMID: 21880848; DOI: 10.3945/ajcn.111.015032.

31. Fiscella K, Winters P, Tancredi D, Hendren S, Franks P. Racial disparity in death from colorectal cancer: does vitamin D deficiency contribute?. Cancer 2011; 117:1061-9; PMID: 20945439; DOI: 10.1002/cncr.25647.

32. Grant WB, Peiris AN. Possible role of serum 25-hydroxyvitamin D in black-white health disparities in the United States. J Am Med Dir Assoc 2010; 11:617-28; PMID: 21029996; DOI: 10.1016/j.jamda.2010.03.013.

33. Avenell A, Maclennan GS, Jenkinson DJ, McPherson GC, McDonald AM, Pant PR, et al. Long-Term Follow-Up for Mortality and Cancer in a Randomized Placebo-Controlled Trial of Vitamin D3 and/or Calcium (RECORD Trial). J Clin Endocrinol Metab 2012; 97:614-22; PMID: 22112804; DOI: 10.1210/jc.2011-1309.

34. Tretli S, Schwartz GG, Torjesen PA, Robsahm TE. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study. Cancer Causes Control 2012; 23:363-70; PMID: 22193397; DOI: 10.1007/s10552-011-9885-6.

35. Porojnicu AC, Dahlback A, Moan J. Sun exposure and cancer survival in Norway: changes in the risk of death with season of diagnosis and latitude. Adv Exp Med Biol 2008; 624:43-54; PMID: 18348446; DOI: 10.1007/978-0-387-77574-6_4.

36. Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control 2004; 15:149-58; PMID: 15017127; DOI: 10.1023/B:CACO.0000019494.34403.09.

37. Porojnicu AC, Lagunova Z, Robsahm TE, Berg JP, Dahlback A, Moan J. Changes in risk of death from breast cancer with season and latitude: sun exposure and breast cancer survival in Norway. Breast Cancer Res Treat 2007; 102:323-8; PMID: 17028983; DOI: 10.1007/s10549-006-9331-8.

38. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol 2009; 27:3757-63; PMID: 19451439; DOI: 10.1200/JCO.2008.20.0725.

39. Kim HJ, Lee YM, Ko BS, Lee JW, Yu JH, Son BH, et al. Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer. Ann Surg Oncol 2011; 18:1830-6; PMID: 21573699; DOI: 10.1245/s10434-010-1465-6.

40. Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res 2011; 13:R74; PMID: 21791049; DOI: 10.1186/bcr2920.

41. Shanafelt TD, Drake MT, Maurer MJ, Allmer C, Rabe KG, Slager SL, et al. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. Blood 2011; 117:1492-8; PMID: 21048153; DOI: 10.1182/blood-2010-07-295683.

42. Moan J, Porojnicu AC, Robsahm TE, Dahlback A, Juzeniene A, Tretli S, et al. Solar radiation, vitamin D and survival rate of colon cancer in Norway. J Photochem Photobiol B 2005; 78:189-93; PMID: 15708515; DOI: 10.1016/j.jphotobiol.2004.11.004.

43. Ng K, Wolpin BM, Meyerhardt JA, Wu K, Chan AT, Hollis BW, et al. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer 2009; 101:916-23; PMID: 19690551; DOI: 10.1038/sj.bjc.6605262.

44. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Season of diagnosis is a prognostic factor in Hodgkin’s lymphoma: a possible role of sun-induced vitamin D. Br J Cancer 2005; 93:571-4; PMID: 16136030; DOI: 10.1038/sj.bjc.6602722.

45. Porojnicu AC, Robsahm TE, Dahlback A, Berg JP, Christiani D, Bruland OS, et al. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role?. Lung Cancer 2007; 55:263-70; PMID: 17207891; DOI: 10.1016/j.lungcan.2006.11.013.

46. Heist RS, Zhou W, Wang Z, Liu G, Neuberg D, Su L, et al. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. J Clin Oncol 2008; 26:5596-602; PMID: 18936471; DOI: 10.1200/JCO.2008.18.0406.

47. Drake MT, Maurer MJ, Link BK, Habermann TM, Ansell SM, Micallef IN, et al. Vitamin D insufficiency and prognosis in non-Hodgkin’s lymphoma. J Clin Oncol 2010; 28:4191-8; PMID: 20713849; DOI: 10.1200/JCO.2010.28.6674.

48. Lagunova Z, Porojnicu AC, Dahlback A, Berg JP, Beer TM, Moan J. Prostate cancer survival is dependent on season of diagnosis. Prostate 2007; 67:1362-70; PMID: 17624920; DOI: 10.1002/pros.20577.

49. Fang F, Kasperzyk JL, Shui I, Hendrickson W, Hollis BW, Fall K, et al. Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer. PLoS One 2011; 6:e18625; PMID: 21494639; DOI: 10.1371/journal.pone.0018625.

50. Bach PB, Schrag D, Brawley OW, Galaznik A, Yakren S, Begg CB. Survival of blacks and whites after a cancer diagnosis. JAMA 2002; 287:2106-13; PMID: 11966385; DOI: 10.1001/jama.287.16.2106.

51. Hollenbeck BK, Dunn RL, Ye Z, Hollingsworth JM, Lee CT, Birkmeyer JD. Racial differences in treatment and outcomes among patients with early stage bladder cancer. Cancer 2010; 116:50-6; PMID: 19877112.

52. Yee DS, Ishill NM, Lowrance WT, Herr HW, Elkin EB. Ethnic differences in bladder cancer survival. Urology 2011; 78:544-9; PMID: 21782222; DOI: 10.1016/j.urology.2011.02.042.

53. Newman LA, Griffith KA, Jatoi I, Simon MS, Crowe JP, Colditz GA. Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status. J Clin Oncol 2006; 24:1342-9; PMID: 16549828; DOI: 10.1200/JCO.2005.03.3472.

54. Berz JP, Johnston K, Backus B, Doros G, Rose AJ, Pierre S, et al. The influence of black race on treatment and mortality for early-stage breast cancer. Med Care 2009; 47:986-92; PMID: 19648837.

55. Schootman M, Jeffe DB, Gillanders WE, Aft R. Racial disparities in the development of breast cancer metastases among older women: a multilevel study. Cancer 2009; 115:731-40; PMID: 19130463; DOI: 10.1002/cncr.24087.

56. Adams SA, Butler WM, Fulton J, Heiney SP, Williams EM, Delage AF, et al. Racial disparities in breast cancer mortality in a multiethnic cohort in the Southeast. Cancer 2011; ; PMID: 21953316; DOI: 10.1002/cncr.26570.

57. Federico C, Alleyn J, Dola C, Tafti S, Galandak J, Jacob C, et al. Relationship among age, race, medical funding, and cervical cancer survival. J Natl Med Assoc 2010; 102:199-205; PMID: 20355349.

58. Du XL, Meyer TE, Franzini L. Meta-analysis of racial disparities in survival in association with socioeconomic status among men and women with colon cancer. Cancer 2007; 109:2161-70; PMID: 17455219; DOI: 10.1002/cncr.22664.

59. Le H, Ziogas A, Taylor TH, Lipkin SM, Zell JA. Survival of distinct Asian groups among colorectal cancer cases in California. Cancer 2009; 115:259-70; PMID: 19109815; DOI: 10.1002/cncr.24034.

60. Soneji S, Iyer SS, Armstrong K, Asch DA. Racial disparities in stage-specific colorectal cancer mortality: 1960-2005. Am J Public Health 2010; 100:1912-6; PMID: 20724684; DOI: 10.2105/AJPH.2009.184192.

61. White A, Vernon SW, Franzini L, Du XL. Racial disparities in colorectal cancer survival: to what extent are racial disparities explained by differences in treatment, tumor characteristics, or hospital characteristics?. Cancer 2010; 116:4622-31; PMID: 20626015; DOI: 10.1002/cncr.25395.

62. Randall TC, Armstrong K. Differences in treatment and outcome between African-American and white women with endometrial cancer. J Clin Oncol 2003; 21:4200-6; PMID: 14615448; DOI: 10.1200/JCO.2003.01.218.

63. Wright JD, Fiorelli J, Schiff PB, Burke WM, Kansler AL, Cohen CJ, et al. Racial disparities for uterine corpus tumors: changes in clinical characteristics and treatment over time. Cancer 2009; 115:1276-85; PMID: 19204905; DOI: 10.1002/cncr.24160.

64. Steyerberg EW, Earle CC, Neville BA, Weeks JC. Racial differences in surgical evaluation, treatment, and outcome of locoregional esophageal cancer: a population-based analysis of elderly patients. J Clin Oncol 2005; 23:510-7; PMID: 15659496; DOI: 10.1200/JCO.2005.05.169.

65. Kim J, Sun CL, Mailey B, Prendergast C, Artinyan A, Bhatia S, et al. Race and ethnicity correlate with survival in patients with gastric adenocarcinoma. Ann Oncol 2010; 21:152-60; PMID: 19622590; DOI: 10.1093/annonc/mdp290.

66. Stessin AM, Sherr DL. Demographic disparities in patterns of care and survival outcomes for patients with resected gastric adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2011; 20:223-33; PMID: 21300617; DOI: 10.1158/1055-9965.EPI-10-0158.

67. Chen LM, Li G, Reitzel LR, Pytynia KB, Zafereo ME, Wei Q, et al. Matched-pair analysis of race or ethnicity in outcomes of head and neck cancer patients receiving similar multidisciplinary care. Cancer Prev Res (Phila) 2009; 2:782-91; PMID: 19737985; DOI: 10.1158/1940-6207.CAPR-09-0154.

68. Keegan TH, Clarke CA, Chang ET, Shema SJ, Glaser SL. Disparities in survival after Hodgkin lymphoma: a population-based study. Cancer Causes Control 2009; 20:1881-92; PMID: 19557531; DOI: 10.1007/s10552-009-9382-3.

69. Hardy D, Xia R, Liu CC, Cormier JN, Nurgalieva Z, Du XL. Racial disparities and survival for nonsmall-cell lung cancer in a large cohort of black and white elderly patients. Cancer 2009; 115:4807-18; PMID: 19626650; DOI: 10.1002/cncr.24521.

70. Sun LM, Li CI, Huang EY, Vaughan TL. Survival differences by race in nasopharyngeal carcinoma. Am J Epidemiol 2007; 165:271-8; PMID: 17090616; DOI: 10.1093/aje/kwk008.

71. Wang M, Burau KD, Fang S, Wang H, Du XL. Ethnic variations in diagnosis, treatment, socioeconomic status, and survival in a large population-based cohort of elderly patients with non-Hodgkin lymphoma. Cancer 2008; 113:3231-41; PMID: 18937267; DOI: 10.1002/cncr.23914.

72. Arbes SJ, Olshan AF, Caplan DJ, Schoenbach VJ, Slade GD, Symons MJ. Factors contributing to the poorer survival of black Americans diagnosed with oral cancer (United States). Cancer Causes Control 1999; 10:513-23; PMID: 10616821; DOI: 10.1023/A:1008911300100.

73. Bristow RE, Ueda S, Gerardi MA, Ajiboye OB, Ibeanu OA. Analysis of racial disparities in stage IIIC epithelial ovarian cancer care and outcomes in a tertiary gynecologic oncology referral center. Gynecol Oncol 2011; 122:319-23; PMID: 21632099; DOI: 10.1016/j.ygyno.2011.04.047.

74. Terplan M, Schluterman N, McNamara EJ, Tracy JK, Temkin SM. Have racial disparities in ovarian cancer increased over time? An analysis of SEER data. Gynecol Oncol 2011; ; PMID: 22108636; DOI: 10.1016/j.ygyno.2011.11.025.

75. Eloubeidi MA, Desmond RA, Wilcox CM, Wilson RJ, Manchikalapati P, Fouad MM, et al. Prognostic factors for survival in pancreatic cancer: a population-based study. Am J Surg 2006; 192:322-9; PMID: 16920426; DOI: 10.1016/j.amjsurg.2006.02.017.

76. Zell JA, Rhee JM, Ziogas A, Lipkin SM, Anton-Culver H. Race, socioeconomic status, treatment, and survival time among pancreatic cancer cases in California. Cancer Epidemiol Biomarkers Prev 2007; 16:546-52; PMID: 17372250; DOI: 10.1158/1055-9965.EPI-06-0893.

77. Evans S, Metcalfe C, Ibrahim F, Persad R, Ben-Shlomo Y. Investigating Black-White differences in prostate cancer prognosis: A systematic review and meta-analysis. Int J Cancer 2008; 123:430-5; PMID: 18452170; DOI: 10.1002/ijc.23500.

78. Cheng I, Witte JS, McClure LA, Shema SJ, Cockburn MG, John EM, et al. Socioeconomic status and prostate cancer incidence and mortality rates among the diverse population of California. Cancer Causes Control 2009; 20:1431-40; PMID: 19526319; DOI: 10.1007/s10552-009-9369-0.

79. Sridhar G, Masho SW, Adera T, Ramakrishnan V, Roberts JD. Do African American men have lower survival from prostate cancer compared with White men? A meta-analysis. Am J Mens Health 2010; 4:189-206; PMID: 20483872; DOI: 10.1177/1557988309353934.

80. Zini L, Perrotte P, Capitanio U, Jeldres C, Duclos A, Arjane P, et al. Race affects access to nephrectomy but not survival in renal cell carcinoma. BJU Int 2009; 103:889-93; PMID: 19021607; DOI: 10.1111/j.1464-410X.2008.08119.x.

81. Sun M, Abdollah F, Liberman D, Abdo A, Thuret R, Tian Z, et al. Racial disparities and socioeconomic status in men diagnosed with testicular germ cell tumors: a survival analysis. Cancer 2011; 117:4277-85; PMID: 21387261; DOI: 10.1002/cncr.25969.

82. Hollenbeak CS, Wang L, Schneider P, Goldenberg D. Outcomes of thyroid cancer in African Americans. Ethn Dis 2011; 21:210-5; PMID: 21749026.

83. Mahdi H, Kumar S, Hanna RK, Munkarah AR, Lockhart D, Morris RT, et al. Disparities in treatment and survival between African American and White women with vaginal cancer. Gynecol Oncol 2011; 122:38-41; PMID: 21497383; DOI: 10.1016/j.ygyno.2011.03.018.

84. Krishnan AV, Trump DL, Johnson CS, Feldman D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am 2010; 39:401-18; PMID: 20511060; DOI: 10.1016/j.ecl.2010.02.011.

85. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 2012; 441:61-76; PMID: 22168439; DOI: 10.1042/BJ20110744.

86. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 2007; 85:860-8; PMID: 17344510.

87. Oh EY, Wood PA, Du-Quiton J, Hrushesky WJ. Seasonal modulation of post-resection breast cancer metastasis. Breast Cancer Res Treat 2008; 111:219-28; PMID: 17934872; DOI: 10.1007/s10549-007-9780-8.

88. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012; 95:91-100; PMID: 22170374; DOI: 10.3945/ajcn.111.014779.

89. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010; 9:709-15; PMID: 20601202; DOI: 10.1016/j.autrev.2010.06.009.

90. Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr 2011; 65:1016-26; PMID: 21731036; DOI: 10.1038/ejcn.2011.68.

91. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010; 106:963-8; PMID: 20854958; DOI: 10.1016/j.amjcard.2010.05.027.

92. Berruti A, Sperone P, Fasolis G, Torta M, Fontana D, Dogliotti L, et al. Pamidronate administration improves the secondary hyperparathyroidism due to “Bone Hunger Syndrome” in a patient with osteoblastic metastases from prostate cancer. Prostate 1997; 33:252-5; PMID: 9397197; DOI: 10.1002/(SICI)1097-0045(19971201)33:4<252: AID-PROS5>3.0.CO;2-J.

93. Coleman RE, McCloskey EV. Bisphosphonates in oncology. Bone 2011; 49:71-6; PMID: 21320652; DOI: 10.1016/j.bone.2011.02.003.

94. Hokugo A, Christensen R, Chung EM, Sung EC, Felsenfeld AL, Sayre JW, et al. Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res 2010; 25:1337-49; PMID: 20200938; DOI: 10.1002/jbmr.23.

95. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ 2010; 340:b5569; PMID: 20093278; DOI: 10.1136/bmj.b5569.

96. Lichtman MA. Obesity and the risk for a hematological malignancy: leukemia, lymphoma, or myeloma. Oncologist 2010; 15:1083-101; PMID: 20930095; DOI: 10.1634/theoncologist.2010-0206.

97. Murthy NS, Mukherjee S, Ray G, Ray A. Dietary factors and cancer chemoprevention: an overview of obesity-related malignancies. J Postgrad Med 2009; 55:45-54; PMID: 19242081; DOI: 10.4103/ 0022-3859.43549 .

98. Drewnowski A. Obesity, diets, and social inequalities. Nutr Rev 2009; 67:S36-9; PMID: 19453676; DOI: 10.1111/j.1753-4887.2009.00157.x.

99. Grant WB. A multicountry ecological study of risk-modifying factors for prostate cancer: apolipoprotein E ?4 as a risk factor and cereals as a risk reduction factor. Anticancer Res 2010; 30:189-99; PMID: 20150635.

100. Lagunova Z, Porojnicu AC, Grant WB, Bruland Ø, Moan JE. Obesity and increased risk of cancer: does decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association?. Mol Nutr Food Res 2010; 54:1127-33; PMID: 20512788.

101. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level: Implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinol 2011; 3:199-204; PMID: 22110780.

102. Lim U, Freedman DM, Hollis BW, Horst RL, Purdue MP, Chatterjee N, et al. A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer 2009; 124:979-86; PMID: 19035445; DOI: 10.1002/ijc.23984.

103. Helzlsouer KJ. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 2010; 172:4-9; PMID: 20562193; DOI: 10.1093/aje/kwq119.

104. Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol 2010; 171:903-8; PMID: 20219763; DOI: 10.1093/aje/kwq005.

105. Grant WB. Benefits of vitamin D in reducing the risk of cancer: Time to include vitamin D in cancer treatment?. J Soc Integr Oncol 2010; 8:81-8.

106. Vashi PG, Trukova K, Lammersfeld CA, Braun DP, Gupta D. Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology. Nutr J 2010; 9:60; PMID: 21092237; DOI: 10.1186/1475-2891-9-60.

107. Peppone LJ, Huston AJ, Reid ME, Rosier RN, Zakharia Y, Trump DL, et al. The effect of various vitamin D supplementation regimens in breast cancer patients. Breast Cancer Res Treat 2011; 127:171-7; PMID: 21384167; DOI: 10.1007/s10549-011-1415-4.

108. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 2009; 7:28; PMID: 19389235; DOI: 10.1186/1479-5876-7-28.

109. Ford ME, Havstad SL, Davis SD. A randomized trial of recruitment methods for older African American men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Clin Trials 2004; 1:343-51; PMID: 16279272; DOI: 10.1191/1740774504cn029oa.

110. Smith AW, Alfano CM, Reeve BB, Irwin ML, Bernstein L, Baumgartner K, et al. Race/ethnicity, physical activity, and quality of life in breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2009; 18:656-63; PMID: 19190157; DOI: 10.1158/1055-9965.EPI-08-0352.

111. Bernstein L, Patel AV, Ursin G, Sullivan-Halley J, Press MF, Deapen D, et al. Lifetime recreational exercise activity and breast cancer risk among black women and white women. J Natl Cancer Inst 2005; 97:1671-9; PMID: 16288120; DOI: 10.1093/jnci/dji374.

112. Esnaola NF, Stewart AK, Feig BW, Skibber JM, Rodriguez-Bigas MA. Age-, race-, and ethnicity-related differences in the treatment of nonmetastatic rectal cancer: a patterns of care study from the national cancer data base. Ann Surg Oncol 2008; 15:3036-47; PMID: 18712449; DOI: 10.1245/s10434-008-0106-9.

113. Rolnick S, Hensley Alford S, Kucera GP, Fortman K, Ulcickas Yood M, Jankowski M, et al. Racial and age differences in colon examination surveillance following a diagnosis of colorectal cancer. J Natl Cancer Inst Monogr 2005; 35:96-101; PMID: 16287893; DOI: 10.1093/jncimonographs/lgi045.

114. Schapira MM, McAuliffe TL, Nattinger AB. Treatment of localized prostate cancer in African-American compared with Caucasian men. Less use of aggressive therapy for comparable disease. Med Care 1995; 33:1079-88; PMID: 7475418; DOI: 10.1097/00005650-199511000-00002.

115. O’Malley MS, Earp JA, Hawley ST, Schell MJ, Mathews HF, Mitchell J. The association of race/ethnicity, socioeconomic status, and physician recommendation for mammography: who gets the message about breast cancer screening?. Am J Public Health 2001; 91:49-54; PMID: 11189825; DOI: 10.2105/AJPH.91.1.49.

116. Sharp LK, Zurawski JM, Roland PY, O’Toole C, Hines J. Health literacy, cervical cancer risk factors, and distress in low-income African-American women seeking colposcopy. Ethn Dis 2002; 12:541-6; PMID: 12477141.

117. Margolis ML, Christie JD, Silvestri GA, Kaiser L, Santiago S, Hansen-Flaschen J. Racial differences pertaining to a belief about lung cancer surgery: results of a multicenter survey. Ann Intern Med 2003; 139:558-63; PMID: 14530226.

118. Holt CL, Wynn TA, Litaker MS, Southward P, Jeames S, Schulz E. A comparison of a spiritually based and non-spiritually based educational intervention for informed decision making for prostate cancer screening among church-attending African-American men. Urol Nurs 2009; 29:249-58; PMID: 19718941.

119. Van Ness PH, Kasl SV, Jones BA. Religion, race, and breast cancer survival. Int J Psychiatry Med 2003; 33:357-75; PMID: 15152786; DOI: 10.2190/LRXP-6CCR-G728-MWYH.

120. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 2008; 264:599-609; PMID: 18793245; DOI: 10.1111/j.1365-2796.2008.02008.x.

121. Boggs DA, Palmer JR, Wise LA, Spiegelman D, Stampfer MJ, Adams-Campbell LL, et al. Fruit and vegetable intake in relation to risk of breast cancer in the Black Women’s Health Study. Am J Epidemiol 2010; 172:1268-79; PMID: 20937636; DOI: 10.1093/aje/kwq293.

122. McLeod DG, Schellhammer PF, Vogelzang NJ, Soloway MS, Sharifi R, Block NL, et al. Exploratory analysis on the effect of race on clinical outcome in patients with advanced prostate cancer receiving bicalutamide or flutamide, each in combination with LHRH analogues. Prostate 1999; 40:218-24; PMID: 10420149; DOI: 10.1002/(SICI)1097-0045(19990901)40:4<218::AID-PROS2>3.0.CO;2-6.

123. Akerley WL, Moritz TE, Ryan LS, Henderson WG, Zacharski LR. Racial comparison of outcomes of male Department of Veterans Affairs patients with lung and colon cancer. Arch Intern Med 1993; 153:1681-8; PMID: 8333805; DOI: 10.1001/archinte.1993. 00410140063008 .

124. Dignam JJ. Differences in breast cancer prognosis among African-American and Caucasian women. CA Cancer J Clin 2000; 50:50-64; PMID: 10735015; DOI: 10.3322/canjclin.50.1.50.

125. Mondul AM, Clipp SL, Helzlsouer KJ, Platz EA. Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort. Cancer Causes Control 2010; 21:61-8; PMID: 19806465; DOI: 10.1007/s10552-009-9434-8.

126. Moses KA, Abd TT, Goodman M, Hsiao W, Hall JA, Marshall FF, et al. Increased low density lipoprotein and increased likelihood of positive prostate biopsy in black americans. J Urol 2009; 182:2219-25; PMID: 19758611; DOI: 10.1016/j.juro.2009.07.039.
-

See any problem with this page? Report it (FINALLY WORKS)