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Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation

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Abstract

Purpose

We conducted a case–control study to examine the role of parents’ nutrient intake before their child’s conception in the child’s risk of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation.

Methods

Parents of 206 cases from 9 North American institutions and 269 friend and relative controls participated; fathers of 182 cases and 223 controls and mothers of 202 cases and 260 controls provided useable information in telephone interviews on their diet in the year before the child’s conception. We also asked parents about supplements, a significant source of nutrients in users.

Results

Father’s intake of dairy-associated nutrients and his use of calcium supplements were associated with decreased risk, while his intake of copper, manganese, and vitamin E was associated with increased risk. Mother’s use of multivitamins close to conception was associated with lower risk as was her intake of several micronutrients found in these supplements. In analyses to elucidate the primary factor from multiple correlated factors, the most robust findings were for father’s calcium intake (adjusted OR = 0.46–0.63 for 700 mg increase) and calcium supplement use (OR = 0.35–0.41) and mother’s multivitamin use (ORs 0.28–0.48).

Conclusions

There are few directly relevant studies but some data indirectly support the biologic plausibility of the inverse associations with father’s calcium intake and mother’s use of multivitamins; however, we cannot rule out contributions of bias, confounding, or chance. Our findings provide a starting point for further investigation of diet in the etiology of retinoblastoma and new germline mutation generally.

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Abbreviations

CI:

Confidence interval

FFQ:

Food frequency questionnaire

NHS:

Nurses’ Health Study

OR:

Odds ratio

References

  1. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:643–646

    Article  PubMed  CAS  Google Scholar 

  2. Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. PNAS 68:820–823

    Article  PubMed  Google Scholar 

  3. Wyrobek AJ, Mulvihill JJ, Wassom JS, Malling HV, Shelby MD, Lewis SE, Witt KL, Preston RJ, Perreault SD, Allen JW, Demarini DM, Woychik RP, Bishop JB (2007) Assessing human germ-cell mutagenesis in the Postgenome Era: a celebration of the legacy of William Lawson (Bill) Russell. Environ Mol Mutagen 48(2):71–95. doi:10.1002/em.20284

    Article  PubMed  CAS  Google Scholar 

  4. Odin AP (1997) Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action. Mutat Res 386:39–67

    Article  PubMed  CAS  Google Scholar 

  5. Kuroda Y, Jaim AK, Tezuka H, Kada T (1992) Antimutagenicity in cultured mammalian cells. Mutat Res 267:201–209

    Article  PubMed  CAS  Google Scholar 

  6. Gaziev AI, Podlutsky AJ, Panfilow BM, Bradbury R (1995) Dietary supplements of antioxidants reduce hprt mutant frequency in splenocytes of aging mice. Mutat Res 338:77–86

    Article  PubMed  CAS  Google Scholar 

  7. Duthie SJ, Ma A, Ross MA, Collins AR (1996) Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res 56:1291–1295

    PubMed  CAS  Google Scholar 

  8. Mayr CA, Woodall AA, Ames BN (2001) DNA damage to sperm from micronutrient deficiency may increase the risk of birth defects and cancer in offspring. In: Bendich A, Deckelbaum RJ (eds) Preventive nutrition: the comprehensive guide for health professionals, 2nd edn. Humana Press, Totowa, pp 373–386

    Google Scholar 

  9. Fraga CG, Motchnik PA, Shigenaga MK, Helbock HJ, Jacob RA, Ames BN (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 88:11003–11006

    Article  PubMed  CAS  Google Scholar 

  10. Xu B, Chia S-E, Tsakok M, Ong C-N (1993) Trace elements in blood and seminal plasma and their relationship to sperm quality. Reprod Toxicol 7:613–618

    Article  PubMed  CAS  Google Scholar 

  11. Oteiza PI, Olin KL, Fraga CG, Keen CL (1995) Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr 125(4):823–829

    PubMed  CAS  Google Scholar 

  12. Young SS, Eskenazi B, Marchetti FM, Block G, Wyrobek AJ (2008) The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod 23(5):1014–1022. doi:10.1093/humrep/den036

    Article  PubMed  CAS  Google Scholar 

  13. James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, Yi P, Tafoya DL, Swenson DH, Wilson VL, Gaylor DW (1999) Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 70(4):495–501

    PubMed  CAS  Google Scholar 

  14. O’Leary VB, Parle-McDermott A, Molloy AM, Kirke PN, Johnson Z, Conley M, Scott JM, Mills JL (2002) MTRR and MTHFR polymorphism: link to Down syndrome? Am J Med Genet 107(2):151–155. doi:10.1002/ajmg.10121

    Article  PubMed  Google Scholar 

  15. Bunin GR, Tseng M, Li Y, Meadows AT, Ganguly A (2012) Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation. Environ Mol Mutagen. doi:10.1002/em.21705

    PubMed  Google Scholar 

  16. Dryja TP, Mukai S, Rapaport JM, Yandell DW (1989) Parental origin of mutations of the retinoblastoma gene. Nature 339:556–558

    Article  PubMed  CAS  Google Scholar 

  17. Zhu XP, Dunn J, Phillips R, Goddard A, Paton K, Becker A, Gallie B (1989) Preferential germline mutation of the paternal allele in retinoblastoma. Nature 340:312–313

    Article  PubMed  CAS  Google Scholar 

  18. Bunin GR, Felice MA, Davidson W, Friedman DL, Shields CL, Maidment A, O’Shea M, Nichols KE, Leahey A, Dunkel IJ, Jubran R, Rodriguez-Galindo C, Schmidt ML, Weinstein JL, Goldman S, Abramson DH, Wilson MW, Gallie BL, Chan HS, Shapiro M, Cnaan A, Ganguly A, Meadows AT (2011) Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation. Int J Cancer 128(10):2393–2404. doi:10.1002/ijc.25565

    Article  PubMed  CAS  Google Scholar 

  19. Bunin GR, Vardhanabhuti S, Lin A, Anschuetz GL, Mitra N (2011) Practical and analytical aspects of using friend controls in case-control studies: experience from a case-control study of childhood cancer. Paediatr Perinat Epidemiol 25(5):402–412. doi:10.1111/j.1365-3016.2011.01210.x

    Article  PubMed  Google Scholar 

  20. Willett W (1998) Food frequency methods. In: Willett W (ed) Nutritional epidemiology, 2nd edn. Oxford University Press, New York, pp 74–100

    Chapter  Google Scholar 

  21. Nichols KEHM, Godmilow L, Bunin G, Shields C, Meadows A, Ganguly A (2005) Sensitive multi-step clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene. Hum Mutat 25:566–574

    Article  PubMed  CAS  Google Scholar 

  22. Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, Han L, Panton R, Branco P, Gallie B (2003) Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am J Hum Genet 72(2):253–269

    Article  PubMed  CAS  Google Scholar 

  23. Willett WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B, Hennekens CH (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122:51–65

    PubMed  CAS  Google Scholar 

  24. Pufulete M (2008) Intake of dairy products and risk of colorectal neoplasia. Nutr Res Rev 21(1):56–67. doi:10.1017/S0954422408035920

    Article  PubMed  CAS  Google Scholar 

  25. Parodi PW (2007) A role for milk proteins and their peptides in cancer prevention. Curr Pharm Des 13(8):813–828

    Article  PubMed  CAS  Google Scholar 

  26. Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN (1996) Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res 351:199–203

    Article  PubMed  Google Scholar 

  27. Bunin GR, Meadows AT, Emanuel BS, Buckley JD, Woods WG, Hammond GD (1989) Pre- and post-conception factors associated with heritable and non-heritable retinoblastoma. Cancer Res 49:5730–5735

    PubMed  CAS  Google Scholar 

  28. Marchetti F, Essers J, Kanaar R, Wyrobek AJ (2007) Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations. Proc Natl Acad Sci USA 104(45):17725–17729. doi:10.1073/pnas.0705257104

    Article  PubMed  CAS  Google Scholar 

  29. Orjuela MA, Titievsky L, Liu X, Ramirez-Ortiz M, Ponce-Castaneda V, Lecona E, Molina E, Beaverson K, Abramson DH, Mueller NE (2005) Fruit and vegetable intake during pregnancy and risk for development of sporadic retinoblastoma. Cancer Epidemiol Biomarkers Prev 14(6):1433–1440

    Article  PubMed  Google Scholar 

  30. Kristal AR, Peters U, Potter JD (2005) Is it time to abandon the food frequency questionnaire? Cancer Epidemiol Biomarkers Prev 14(12):2826–2828

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the US National Institutes of Health (R01CA081012 and R01CA118580). We are grateful to the families of the patients and their relatives and friends for their participation. We thank Drs. Debra Friedman, Carol Shields, Kim Nichols, Ann Leahey, Ira Dunkel, Rima Jubran, Carlos Rodriguez-Galindo, Mary Lou Schmidt, Joanna Weinstein, Stewart Goldman, David Abramson, Matthew Wilson, Brenda Gallie, Helen Chan, and Michael Shapiro for enrolling and caring for the patients and Drs. Avital Cnaan and Larry Kushi for their assistance in the design of the study. We also thank the clinical research staff at the participating centers and study staff at Children’s Hospital of Philadelphia for their diligent efforts particularly Bethany Barone, Jaclyn Bosco, Greta Anschuetz, Sheila Kearney, and the late Jean Rodwell.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Oncology, Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Greta R. Bunin, Yimei Li & Anna T. Meadows

  2. Department of Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Arupa Ganguly

  3. Department of Kinesiology, California Polytechnic University, San Luis Obispo, CA, 93401, USA

    Marilyn Tseng

Authors
  1. Greta R. Bunin
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  2. Yimei Li
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  3. Arupa Ganguly
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  4. Anna T. Meadows
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  5. Marilyn Tseng
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Correspondence to Greta R. Bunin.

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Bunin, G.R., Li, Y., Ganguly, A. et al. Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation. Cancer Causes Control 24, 343–355 (2013). https://doi.org/10.1007/s10552-012-0120-x

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  • DOI: https://doi.org/10.1007/s10552-012-0120-x

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