Validating a breast cancer score in Spanish women. The MCC-Spain study

Abstract

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations.

Cancer‐specific risk prediction with a serum microRNA signature

“…In a previous study 11 from our research group, we assessed associations of a PRS, ERS, and methylation risk scores (MRSs), with BC incidence in the ESTHER cohort with up to 14 years of follow‐up. While the PRS (based on 269 single‐nucleotide polymorphisms (SNPs) derived from a GWAS 48 ) and ERS (Dierssen–Sotos score 49 ) showed positive individual associations with BC incidence, the MRS (based on 423 CpGs, derived from genetically predicted cytosine‐phosphate‐guanine (CpG) methylation levels 50 ) was not significantly associated with BC incidence. Adjusted ORs per SD increase in the score were 1.48 (95% CI, 1.16–1.90), 1.40 (95% CI, 1.09–1.80), and 1.07 (95% CI, 0.84–1.36) for the PRS, ERS, and MRS, respectively.…”

The association of female reproductive factors with history of cardiovascular disease: a large cross-sectional study

“…As a result, pregnancy may have long-term effects on the cardiovascular system. Many risk factors have been identified through epidemiological research (age at menarche, parity, age at first full-term pregnancy, age at menopause), most of which are related to estrogen production [ 53 ]. Feng X and his team found that pregnant women’s estrogen and progesterone levels increase rapidly during pregnancy [ 54 ].…”

Cohort profile: the MCC-Spain follow-up on colorectal, breast and prostate cancers: study design and initial results

“…The MCC-Spain has provided results on the effects of different risk factors. For instance, night shift work increased the risk of more aggressive prostate cancers,23 although this excess risk almost disappeared 20 years after last exposure24; long-term consumption of calcium channel blockers was associated with higher breast cancer risk in overweight women25; adherence to the Western dietary patterns increased breast cancer risk in both premenopausal and postmenopausal women26; first validation in a European population of a risk model for breast cancer developed in American women using both modifiable and non-modifiable risk factors as well as 92 genetic variants27; use of environmental and genetic factors to elaborate a model to stratify the risk of colorectal cancer28; and adherence to the World Cancer Research Fund/American Institute for Cancer Research nutrition-based guidelines was associated with lower risk of colorectal and breast cancers, but not of prostate cancer 29. A complete list of published results from MCC-Spain appears in online supplementary table 2 and supplementary reference list.…”