| Autor: |
Yutaka Yasui, Letsou, William, Fan Wang, Im, Cindy, Sapkota, Yadav, Zhaoming Wang, Salehabadi, Sedigheh Mirzaei, Baedke, Jessica L., Won Jong Moon, Qi Liu, Robison, Leslie L., Martinez, Jose Miguel |
| Zdroj: |
Cancer Epidemiology, Biomarkers & Prevention; Nov2023, Vol. 32 Issue 11, p1518-1523, 6p |
| Abstrakt: |
Background: What are the major determinants of women's breast cancer risk? Rare mutations such as those in the BRCA1/2 genes, polygenic scores of common alleles identified by genome-wide association studies, or nongenetic factors? Methods: The population-based Nordic Twin Study of Cancer, with 3,933 breast cancer cases among 21,054 monozygotic (MZ) and 30,939 dizygotic (DZ) female twin pairs, provides three key clues to this question: (i) the average lifetime risk, approximately 8%, does not differ by twin zygosity; (ii) the mean time interval between diagnoses when both twins develop disease (i.e., disease concordance) also does not differ by zygosity; but, (iii) conditioning on one twin having developed disease, the incidence rate in the co-twin is approximately 1% per year if the pair is MZ and 0.5% per year if DZ. Results: Assuming that nongenetic risk factors are shared similarly between twins regardless of zygosity, we can draw two conclusions from (i) to (iii). Conclusions: First, (i) and (iii) imply that the chief determinant of risk is in the germline DNA, because the conditional incidence rate is several-fold higher than the average risk (8% lifetime) in MZ twins but only half as much in DZ twins. Second, the seeming inconsistency between the two-fold conditional incidence rate (iii) and the equality of the mean inter-twin disease intervals in disease concordance (ii) can be resolved if the risk factors in the germline DNA are rare variants, not common variants. Impact: This paper details simple deductive reasoning for these conclusions and draws a critical inference regarding breast cancer etiology. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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