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Serum 25-hydroxyvitamin D concentrations and lung cancer risk in never-smoking postmenopausal women

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Abstract

Purpose

Vitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations.

Methods

In the Women’s Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers. Baseline serum 25(OH)D was assayed by a chemiluminescent method. Logistic regression was used to estimate odds ratios (ORs) for quartiles and predefined clinical cutoffs of serum 25(OH)D concentrations.

Results

Comparing quartiles 4 versus 1 of serum 25(OH)D concentrations, ORs were 1.06 [95% confidence interval (CI) 0.61–1.84] for all lung cancer, 0.94 (95% CI 0.52–1.69) for NSCLC, and 0.91 (95% CI 0.49–1.68) for adenocarcinoma. Comparing serum 25(OH)D ≥ 75 (high) versus <30 nmol/L (deficient), ORs were 0.76 (95% CI 0.31–1.84) for all lung cancer, 0.71 (95% CI 0.27–1.86) for NSCLC, and 0.81 (95% CI 0.31–2.14) for adenocarcinoma. There is suggestive evidence that CaD supplementation (1 g calcium + 400 IU D3/day) and a high level of circulating vitamin A may modify the associations of 25(OH)D with lung cancer overall and subtypes (p interaction <0.10).

Conclusions

In this group of never-smoking postmenopausal women, the results did not support the hypothesis of an association between serum 25(OH)D and lung cancer risk.

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References

  1. Samet JM, Avila-Tang E, Boffetta P et al (2009) Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res 15:5626–5645

    Article  PubMed  PubMed Central  Google Scholar 

  2. Menezes RJ, Cheney RT, Husain A et al (2008) Vitamin D receptor expression in normal, premalignant, and malignant human lung tissue. Cancer Epidemiol Biomarkers Prev 17:1104–1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW (2008) Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol (Baltimore Md 1950) 181:7090–7099

    Article  CAS  Google Scholar 

  4. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  PubMed  Google Scholar 

  5. Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7:684–700

    Article  CAS  PubMed  Google Scholar 

  6. Carlberg C, Bendik I, Wyss A et al. (1993) Two nuclear signaling pathways for vitamin D. Nature 361:657–360

    Article  CAS  PubMed  Google Scholar 

  7. Pereira F, Larriba MJ, Munoz A (2012) Vitamin D and colon cancer. Endocr Relat Cancer 19:R51–R71

    Article  CAS  PubMed  Google Scholar 

  8. Kilkkinen A, Knekt P, Heliövaara M et al (2008) Vitamin D status and the risk of lung cancer: a cohort study in Finland. Cancer Epidemiol Biomarkers Prev 17:3274–3278

    Article  CAS  PubMed  Google Scholar 

  9. Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI (2010) Serum vitamin D and cancer mortality in the NHANES III Study (1988–2006). Cancer Res 70:8587–8597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cheng TY, Neuhouser ML (2012) Serum 25-hydroxyvitamin D, interaction with vitamin A and lung cancer mortality in the U.S. population. Cancer Causes Control 23:1557–1565

    Article  PubMed  Google Scholar 

  11. Giovannucci E, Liu Y, Rimm EB et al (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98:451–459

    Article  CAS  PubMed  Google Scholar 

  12. Weinstein SJ, Yu K, Horst RL, Parisi D, Virtamo J, Albanes D (2011) Serum 25-hydroxyvitamin d and risk of lung cancer in male smokers: a nested case–control study. PLoS ONE 6:e20796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Skaaby T, Husemoen LL, Thuesen BH et al (2014) Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev 23:1220–1229

    Article  CAS  PubMed  Google Scholar 

  14. Ordonez-Mena JM, Schottker B, Haug U et al. (2013) Serum 25-hydroxyvitamin d and cancer risk in older adults: results from a large German prospective cohort study. Cancer Epidemiol Biomarkers Prev 22:905–916

    Article  CAS  PubMed  Google Scholar 

  15. Ordonez-Mena JM, Schottker B, Fedirko V et al. (2015) Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium. Eur J Epidemiol. doi:10.1007/s10654-015-0040-7

    PubMed  Google Scholar 

  16. Afzal S, Bojesen SE, Nordestgaard BG. (2013) Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. Clin Chem 59:771–780

    Article  CAS  PubMed  Google Scholar 

  17. Wong YY, Hyde Z, McCaul KA et al (2014) In older men, lower plasma 25-hydroxyvitamin D is associated with reduced incidence of prostate, but not colorectal or lung cancer. PLoS ONE 9:e99954

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chen GC, Zhang ZL, Wan Z et al (2015) Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis. Cancer Causes Control 26:1719–1728

    Article  CAS  PubMed  Google Scholar 

  19. The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19:61–109

    Article  Google Scholar 

  20. Jackson RD, LaCroix AZ, Gass M et al. (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683

    Article  CAS  PubMed  Google Scholar 

  21. Wactawski-Wende J, Kotchen JM, Anderson GL et al. (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354:684–696

    Article  CAS  PubMed  Google Scholar 

  22. Hays J, Hunt JR, Hubbell FA et al (2003) The Women’s Health Initiative recruitment methods and results. Ann Epidemiol 13:S18–S77

    Article  PubMed  Google Scholar 

  23. Curb JD, McTiernan A, Heckbert SR et al (2003) Outcomes ascertainment and adjudication methods in the Women’s Health Initiative. Ann Epidemiol 13:S122-8

    Article  PubMed  Google Scholar 

  24. Luo J, Margolis KL, Wactawski-Wende J et al (2011) Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ 342:d1016

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bondy SJ, Victor JC, Diemert LM. (2009) Origin and use of the 100 cigarette criterion in tobacco surveys. Tob Control 18:317–323

    Article  CAS  PubMed  Google Scholar 

  26. Krasinski SD, Russell RM, Otradovec CL et al. (1989) Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users. Am J Clin Nutr 49:112–120

    CAS  PubMed  Google Scholar 

  27. Ballew C, Galuska D, Gillespie C (2001) High serum retinyl esters are not associated with reduced bone mineral density in the Third National Health And Nutrition Examination Survey, 1988–1994. J Bone Miner Res 16:2306–2312

    Article  CAS  PubMed  Google Scholar 

  28. Bauer SR, Richman EL, Sosa E et al (2013) Antioxidant and vitamin E transport genes and risk of high-grade prostate cancer and prostate cancer recurrence. Prostate 73:1786–1795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9:178–187

    Article  CAS  PubMed  Google Scholar 

  30. Patterson RE, Levy L, Tinker LF, Kristal AR (1999) Evaluation of a simplified vitamin supplement inventory developed for the Women’s Health Initiative. Public Health Nutr 2:273–276

    Article  CAS  PubMed  Google Scholar 

  31. Wang Y, Jacobs EJ, McCullough ML et al (2009) Comparing methods for accounting for seasonal variability in a biomarker when only a single sample is available: insights from simulations based on serum 25-hydroxyvitamin d. Am J Epidemiol 170:88–94

    Article  PubMed  Google Scholar 

  32. Institute of Medicine (2011) Dietary reference intake for calcium and vitamin D. The National Academics Press, Washington, DC

    Google Scholar 

  33. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28

    CAS  PubMed  Google Scholar 

  34. Maldonado G, Greenland S (1993) Simulation study of confounder-selection strategies. Am J Epidemiol 138:923–936

    Article  CAS  PubMed  Google Scholar 

  35. Cheng TY, Millen AE, Wactawski-Wende J et al (2014) Vitamin D intake determines vitamin d status of postmenopausal women, particularly those with limited sun exposure. J Nutr 144:681–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Schnatz PF, Jiang X, Vila-Wright S et al. (2014) Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial. Menopause 21:823–833

    Article  PubMed  PubMed Central  Google Scholar 

  37. Giovannucci E (2007) Can vitamin D reduce total mortality? Arch Intern Med 167:1709–1710

    Article  PubMed  Google Scholar 

  38. Brunner RL, Wactawski-Wende J, Caan BJ et al. (2011) The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women’s Health Initiative (WHI) calcium plus vitamin D randomized clinical trial. Nutr Cancer 63:827–841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pradhan AD, Manson JE (2016) Update on the vitamin D and omega-3 trial (VITAL). J Steroid Biochem Mol Biol 155:252–256

    Article  CAS  PubMed  Google Scholar 

  40. Cheng TY, Lacroix AZ, Beresford SA et al (2013) Vitamin D intake and lung cancer risk in the Women’s Health Initiative. Am J Clin Nutr 98:1002–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang Q, Kanterewicz B, Shoemaker S et al. (2013) Differential response to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) in non-small cell lung cancer cells with distinct oncogene mutations. J Steroid Biochem Mol Biol 136:264–270

    Article  CAS  PubMed  Google Scholar 

  42. Tong WM, Hofer H, Ellinger A, Peterlik M, Cross HS (1999) Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: relevance for suppression of epidermal growth factor-stimulated cell growth. Oncol Res 11:77–84

    CAS  PubMed  Google Scholar 

  43. Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359:1367–1380

    Article  CAS  PubMed  Google Scholar 

  44. Kaiser U, Schilli M, Wegmann B et al (1996) Expression of vitamin D receptor in lung cancer. J Cancer Res Clin Oncol 122:356–359

    Article  CAS  PubMed  Google Scholar 

  45. Cheng TY, Goodman GE, Thornquist MD et al (2014) Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers. Int J Cancer 135:2135–2145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cheng TY, Cramb SM, Baade PD, Youlden DR, Nwogu C, Reid ME (2016) The international epidemiology of lung cancer: latest trends, disparities, and tumor characteristics. J Thorac Oncol 11:1653–1671

    Article  PubMed  Google Scholar 

  47. Sun S, Schiller JH, Gazdar AF. (2007) Lung cancer in never smokers–a different disease. Nat Rev Cancer 7:778–790

    Article  CAS  PubMed  Google Scholar 

  48. Meng JE, Hovey KM, Wactawski-Wende J et al. (2012) Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women. Cancer Epidemiol Biomarkers Prev 21:916–924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Xiaojun Hu and Pamela Y. Yang for their technical assistance with the lab assays and Hui-Chun Tammy Hsu for her statistical assistance. We also thank WHI participants and the Program Office; Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller (National Heart, Lung, and Blood Institute, Bethesda, MD); Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg (the Clinical Coordinating Center at Fred Hutchinson Cancer Research Center, Seattle, WA); the Investigators and Academic Centers; JoAnn E Manson (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA); Barbara V Howard (MedStar Health Research Institute/Howard University, Washington, DC); Marcia L Stefanick (Stanford Prevention Research Center, Stanford, CA); Rebecca Jackson (The Ohio State University, Columbus, OH); Cynthia A Thomson (University of Arizona, Tucson/Phoenix, AZ); Marian Limacher (University of Florida, Gainesville/Jacksonville, FL); Robert Wallace (University of Iowa, Iowa City/Davenport, IA); Lewis Kuller (University of Pittsburgh, Pittsburgh, PA); Sally Shumaker (Wake Forest University School of Medicine, Winston-Salem, NC).

Funding

This work was supported by NIH/NCI grants R03CA167696 and K07CA201334. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

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Correspondence to Ting-Yuan David Cheng.

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Cheng, TY.D., Song, X., Beresford, S.A.A. et al. Serum 25-hydroxyvitamin D concentrations and lung cancer risk in never-smoking postmenopausal women. Cancer Causes Control 28, 1053–1063 (2017). https://doi.org/10.1007/s10552-017-0956-1

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