Investigating the Relationship between Birthweight and Breast Cancer from A Non-Linear and Mediation Perspective
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Abstract
Background: Epidemiological studies have shown a positive relationship between birthweight and breast cancer; however, inconsistent, sometimes even controversial, observations emerged. We re-explored the association between them in the UK Biobank cohort.
Methods: Relying on the UK Biobank cohort data of white British volunteers recruited between 2006 and 2010 (5,760 cases and 162,778 controls), we evaluated the causal mediation between birthweight and breast cancer, with age of menarche and age at menopause as two potential mediators under the traditional mediation analysis framework. The non-linear relationship between birthweight and breast cancer was also investigated by including the square of birthweight or discretized birthweight categories (<2.5, 2.5~4.0, or >4.0). Furthermore, we performed a stratification analysis in terms of the menopause status.
Results: Birthweight can indirectly influence breast cancer risk in adulthood via the path of age of menarche or age at menopause, and found statistical evidence supporting the existence of suggestive non-linear association between birthweight and breast cancer (β=0.062 and P=0.004 for the square of birthweight) although failing to discover a linear relationship (P=0.230). We also demonstrated such non-linear association seemed more pronounced and robust for premenopausal women compared with postmenopausal ones (27.5% vs. 19.5% increase in breast cancer risk).
Conclusion: This study provided an in-depth insight into the observed relationship between birthweight and breast cancer and revealed that non-linear impact and causal mediation commonly drive the connection between the two traits.
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25. MacKinnon DP, Lockwood CM, Hoffman JM, et al (2002). A comparison of methods to test mediation and other intervening variable effects. Psychol Methods, 7(1):83-104.
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27. Petridou E, Panagiotopoulou K, Katsouyanni K, et al (1990). Tobacco smoking, pregnancy estrogens, and birth weight. Epidemiology, 1(3):247-50.
28. Wang HS, Chard T (1992). The role of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in the control of human fetal growth. J Endocrinol, 132(1):11-9.
29. Kazer RR (1995). Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis. Int J Cancer, 62(4):403-6.
30. Pezzino V, Papa V, Milazzo G, et al (1996). Insulin-like growth factor-I (IGF-I) receptors in breast cancer. Ann N Y Acad Sci, 784:189-201.
31. McCormack VA, dos Santos Silva I, De Stavola BL, et al (2003). Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort. BMJ, 326(7383):248.
32. Park SK, Garcia‐Closas M, Lissowska J, et al (2006). Intrauterine environment and breast cancer risk in a population‐based case‐control study in Poland. Int J Cancer, 119(9):2136-41.
33. Ekbom A, Hsieh CC, Lipworth L, et al (1997). Intrauterine environment and breast cancer risk in women: a population-based study. J Natl Cancer Inst, 89(1):71-6.
34. Monninkhof EM, van der Schouw YT, Peeters PH (1999). Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort. Breast Cancer Res Treat, 55(3):285-91.
35. Parks RM, Derks MGM, Bastiaannet E, et al (2018). Breast Cancer Epidemiology. In: Wyld L, Markopoulos C, Leidenius M, Senkus-Konefka E, editors. Breast Cancer Management for Surgeons: A European Multidisciplinary Textbook. Cham: Springer International Publishing. p. 19-29.
36. Lipworth L (1995). Epidemiology of breast cancer. Eur J Cancer, 4(1):7-30.
37. Chang-Claude J, Andrieu N, Rookus M, et al (2007). Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev, 16(4):740-6.
38. Ruder EH, Dorgan JF, Kranz S, et al (2008). Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence. Clin Breast Cancer, 8(4):334-42.
2. Anbazhagan R, Gusterson BA (1994). Prenatal factors may influence predisposition to breast cancer. Eur J Cancer, 30A(1):1-3.
3. Sanderson M, Williams MA, Malone KE, et al (1996). Perinatal factors and risk of breast cancer. Epidemiology, 7(1):34-7.
4. Kaijser M, Lichtenstein P, Granath F, et al (2001). In utero exposures and breast cancer: a study of opposite-sexed twins. J Natl Cancer Inst, 93(1):60-2.
5. Michels KB, Xue F, Terry KL, et al (2006). Longitudinal study of birthweight and the incidence of breast cancer in adulthood. Carcinogenesis, 27(12):2464-8.
6. Xu X, Dailey AB, Peoples-Sheps M, et al (2009). Birth weight as a risk factor for breast cancer: a meta-analysis of 18 epidemiological studies. J Womens Health (Larchmt), 18(8):1169-78.
7. Zhou W, Chen X, Huang H, et al (2020). Birth Weight and Incidence of Breast Cancer: Dose-Response Meta-analysis of Prospective Studies. Clin Breast Cancer, 20(5):e555-e568.
8. Vatten LJ, Maehle BO, Lund Nilsen TI, et al (2002). Birth weight as a predictor of breast cancer: a case-control study in Norway. Br J Cancer, 86(1):89-91.
9. Mellemkjær L, Olsen ML, Sørensen HT, et al (2003). Birth weight and risk of early-onset breast cancer (Denmark). Cancer Causes Control, 14(1):61-4.
10. Ahlgren M, Sørensen T, Wohlfahrt J, et al (2003). Birth weight and risk of breast cancer in a cohort of 106,504 women. Int J Cancer, 107(6):997-1000.
11. Ahlgren M, Melbye M, Wohlfahrt J, et al (2004). Growth Patterns and the Risk of Breast Cancer in Women. N Engl J Med, 351(16):1619-26.
12. dos Santos Silva I, De Stavola BL, Hardy RJ, et al (2004). Is the association of birth weight with premenopausal breast cancer risk mediated through childhood growth? Br J Cancer, 91(3):519-24.
13. Swerdlow AJ, Wright LB, Schoemaker MJ, et al (2018). Maternal breast cancer risk in relation to birthweight and gestation of her offspring. Breast Cancer Res, 20(1):110.
14. Barber LE, Bertrand KA, Rosenberg L, et al (2019). Pre- and perinatal factors and incidence of breast cancer in the Black Women's Health Study. Cancer Causes Control, 30(1):87-95.
15. da Cruz RS, Carney EJ, Clarke J, et al (2018). Paternal malnutrition programs breast cancer risk and tumor metabolism in offspring. Breast Cancer Res, 20(1):99.
16. Bukowski R, Chlebowski RT, Thune I, et al (2012). Birth weight, breast cancer and the potential mediating hormonal environment. PLoS One, 7(7):e40199.
17. Sudlow C, Gallacher J, Allen N, et al (2015). UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med, 12(3):e1001779.
18. Yang S, Zhou X (2020). Accurate and Scalable Construction of Polygenic Scores in Large Biobank Data Sets. Am J Hum Genet, 106(5):679-93.
19. VanderWeele T (2015). Explanation in causal inference: methods for mediation and interaction: Oxford University Press.
20. Zeng P, Shao Z, Zhou X (2021). Statistical methods for mediation analysis in the era of high-throughput genomics: current successes and future challenges. Comput Struct Biotechnol J, 19:3209-24.
21. Baron RM, Kenny DA (1986). The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. J Pers Soc Psychol, 51(6):1173-82.
22. Daniel RM, De Stavola BL, Cousens SN, et al (2015). Causal mediation analysis with multiple mediators. Biometrics, 71(1):1-14.
23. Ihaka R, Gentleman R (1996). R: A Language for Data Analysis and Graphics. J Comput Graph Statist, 5(3):299-314.
24. Kar SP, Andrulis IL, Brenner H, et al (2019). The association between weight at birth and breast cancer risk revisited using Mendelian randomisation. Eur J Epidemiol, 34(6):591-600.
25. MacKinnon DP, Lockwood CM, Hoffman JM, et al (2002). A comparison of methods to test mediation and other intervening variable effects. Psychol Methods, 7(1):83-104.
26. MacKinnon DP (2008). Introduction to statistical mediation analysis: Routledge.
27. Petridou E, Panagiotopoulou K, Katsouyanni K, et al (1990). Tobacco smoking, pregnancy estrogens, and birth weight. Epidemiology, 1(3):247-50.
28. Wang HS, Chard T (1992). The role of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in the control of human fetal growth. J Endocrinol, 132(1):11-9.
29. Kazer RR (1995). Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis. Int J Cancer, 62(4):403-6.
30. Pezzino V, Papa V, Milazzo G, et al (1996). Insulin-like growth factor-I (IGF-I) receptors in breast cancer. Ann N Y Acad Sci, 784:189-201.
31. McCormack VA, dos Santos Silva I, De Stavola BL, et al (2003). Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort. BMJ, 326(7383):248.
32. Park SK, Garcia‐Closas M, Lissowska J, et al (2006). Intrauterine environment and breast cancer risk in a population‐based case‐control study in Poland. Int J Cancer, 119(9):2136-41.
33. Ekbom A, Hsieh CC, Lipworth L, et al (1997). Intrauterine environment and breast cancer risk in women: a population-based study. J Natl Cancer Inst, 89(1):71-6.
34. Monninkhof EM, van der Schouw YT, Peeters PH (1999). Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort. Breast Cancer Res Treat, 55(3):285-91.
35. Parks RM, Derks MGM, Bastiaannet E, et al (2018). Breast Cancer Epidemiology. In: Wyld L, Markopoulos C, Leidenius M, Senkus-Konefka E, editors. Breast Cancer Management for Surgeons: A European Multidisciplinary Textbook. Cham: Springer International Publishing. p. 19-29.
36. Lipworth L (1995). Epidemiology of breast cancer. Eur J Cancer, 4(1):7-30.
37. Chang-Claude J, Andrieu N, Rookus M, et al (2007). Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev, 16(4):740-6.
38. Ruder EH, Dorgan JF, Kranz S, et al (2008). Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence. Clin Breast Cancer, 8(4):334-42.
| Files | ||
| Issue | Vol 53 No 1 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i1.14695 | |
| Keywords | ||
| breast cancer birthweight UK Biobank non-linear association mediation analysis | ||
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How to Cite
1.
Zhang M, Qiao J, Zeng P, Liu Z. Investigating the Relationship between Birthweight and Breast Cancer from A Non-Linear and Mediation Perspective. Iran J Public Health. 2024;53(1):187-197.
