Digit ratio (2D:4D) is associated with breast cancer

Patrícia Helena Costa Mendes, Ana Carolina de Campos Gomes, Priscila Bernadina Miranda Soares, Eduardo Gonçalves, Clayton Paraíso Macedo, Marise Fagundes Silveira, Daniella Reis Barbosa Martelli, Lívia Máris Ribeiro Paranaíba, Hercílio Martelli-Júnior

Abstract


Purpose: Digit ratio (2D:4D) has been considered as a proxy biomarker for prenatal hormonal exposure and may represent an individual’s predisposition to breast cancer. The purpose of the present study is to investigate whether there is a link between digit ratio and breast cancer in a Brazilian population.

Methods: Digital measurements of the lengths of the index and ring fingers of both hands were obtained from women with breast cancer (n = 100) and age-matched controls (n = 100) using a digital Vernier calliper. Mean digit ratios of right hands, left hands, and right minus left hand 2D:4D (DR-L) were compared between both groups. Data were analysed by the Student's t-test for unpaired samples, Mann-Whitney test, and Spearman`s correlation with a significance level of 5%.

Results: The patients with breast cancer presented significantly higher right and left 2D:4D (both p < 0.001) and higher DR-L (p = 0.032) than controls. Among breast cancer cases, there was a significantly negative correlation between left 2D:4D and age diagnosed with breast cancer (p = 0.018).

Conclusion: Digit ratio offers a valid retrospective biomarker of action of prenatal hormones and might be associated with breast cancer risk and age at onset of breast cancer. It suggests that higher exposure or sensitivity to prenatal oestrogen might be associated with a higher risk of breast cancer and with earlier onset of the disease.


Keywords


Digit Ratio, 2D:4D, Intrauterine Oestrogen, Breast Cancer

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References


Potischman N, Troisi R, Vatten L. The life course approach to cancer epidemiology. In: Kuh D, Ben-Shlomo Y, editors. A life course approach to chronic disease epidemiology. New York: Oxford University Press;2004.

Trichopoulos D. Hypothesis: does breast cancer originate in utero. Lancet. 1990;335(8695): 939-40.

Park SK, Kang D, McGlynn KA, et al. Intrauterine environments and breast cancer risk: meta-analysis and systematic review. Breast Cancer Res. 2008;10(1):1-8.

Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med. 2006; 354(3): 270–82.

Trichopoulos D. Intrauterine environment, mammary gland mass and breast cancer risk. Breast Cancer Res. 2003;5(1):42-4.

Manning JT, Scutt D, Wilson J, Lewis-Jones DI. The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinising hormone and oestrogen. Hum Reprod. 1998;13(11):3000-4.

Manning JT, Callow M, Bundred PE. Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes. Med Hypotheses. 2003;60(3):340-3.

Breedlove SM. Minireview: Organizational hypothesis: instances of the fingerpost. Endocrinology 2010;151(9):4116-22.

Manning JT, Bundred PE. The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 2000;54(5):855-7.

Hopp RN, Lima N, Filho J, et al. Digit Ratio (2D:4D) and cancer: What is known so far? Int J Cancer Ther Oncol. 2014; 2(1):020111.

Mendes PHC, Martelli DRB, Costa SM, et al. Comparison of digit ratio (2D:4D) between Brazilian men with and without prostate cancer. Prostate Cancer Prostatic Dis. 2016;19(1):107-10.

Jung H, Kim KH, Yoon SJ, Kim TB. Second to fourth digit ratio: a predictor of prostate-specific antigen level and the presence of prostate cancer. BJU Int. 2010;107(4):591-6.

Rahman AA, Lophatananon A, Stewart-Brown S, Harriss D, Anderson J, Parker T, et al. Hand pattern indicates prostate cancer risk. Br J Cancer. 2011;104(1):175-7.

Manning JT, Leinster S. The ratio of 2nd to 4th digit length and age at presentation of breast cancer: a link with prenatal oestrogen. Breast. 2001;10(4):355-7.

Muller DC, Baglietto L, Manning JT, et al. Second to fourth digit ratio (2D:4D), breast cancer risk factors, and breast cancer risk: a prospective cohort study. Br J Cancer. 2012; 107(9):1631-6.

Hong L, Zhan-Bing M, Zhi-Yun S, et al. Digit ratio (2D:4D) in Chinese women with breast cancer. Am J Hum Biol. 2014;26(4):562-4.

Hopp RN, Lima NCDS, Filho JLF, et al. Digit ratio (2D:4D) is associated with gastric cancer. Early Hum Develop. 2013;89(5):327-9.

Hopp RN, Lima NCDS, Filho MS, et al. Digit ratio is associated with colorectal cancer. J Gastrointest Dig Syst. 2015;5(1):1-14.

Hopp RN, Jorge J. Right hand digit ratio (2D:4D) is associated with oral cancer. Am J Hum Biol. 2011; 23(3):423-5.

Zheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios. Proc Natl Acad Sci USA. 2011;108(39):16289-94.

Eblaghie MC, Song SJ, Kim JY, et al. Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos. J Anat. 2004;205(1):1–13.

Raman V, Martensen SA, Reisman D, et al. Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature. 2000;405(6789):974-8.

Zhang X, Zhu T, Chen Y, et al. Human Growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. J Bio Chem. 2003;278(9):7580-90.

Chakravarty G, Moroz K, Makridakis NM, et al. Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer. Exp Biol Med. 2011; 236(2):145-55.

Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90.

National Cancer Institute. Estimate 2014: incidence of cancer in Brazil. National Cancer Institute José Alencar Gomes da Silva: Rio de Janeiro, Brazil, 2014.

Ribeiro E, Neave N, Morais RN, Manning JT. Direct versus indirect measurement of digit ratio (2D:4D); a clinical review of the literature and new data. Evol Psychol. 2016;14(1):1-8.

Arango HG. Biostatistics – Theoretical and computational. Nova Guanabara: Rio de Janeiro, Brazil, 2009.

Manning JT. Digit ratio: a pointer to fertility, behaviour and health. New Brunswick: Rutgers University Press, 2002.

Manning JT. The finger ratio. London: Faber and Faber, 2008.

Waters M, Rebholz CM, Wood B, et al. Second to fourth digit ratio and prostate cancer severity. Prostate Cancer Prostatic Dis. 2013;16(1):107-10.

Hopp RN, Jorge J. Right hand digit ratio (2D:4D) is associated with prostate cancer: Findings of an admixed population study. J Solid Tumors. 2012;2(1):22-5.

Hönekopp J, Watson S. Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand. Am J Hum Biol. 2010;22(5):619-30.

Hurd PL, Vaillancourt KL, Dinsdale NL. Aggression, digit ratio and variation in androgen receptor and monoamine oxidase a genes in men. Behav Genet. 2011;41(4):543–6.

Pena SD, Di Pietro G, Fuchshuber-Moraes M, et al. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS One. 2011; 6(2):e17063.

Moura RR, Coelho AVC, Balbino VQ, et al. Meta-analysis of Brazilian genetic admixture and comparison with other Latin America countries. Am J Hum Biol. 2015;27(5):674-80.

Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis 2006;21(3):427-33.




DOI: http://dx.doi.org/10.14319/ijcto.43.8

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