A Personal Breast Cancer Risk Stratification Model Using Common Variants and Environmental Risk Factors in Japanese Females

Abstract

Personalized approaches to prevention based on genetic risk models have been anticipated, and many models for the prediction of individual breast cancer risk have been developed. However, few studies have evaluated personalized risk using both genetic and environmental factors. We developed a risk model using genetic and environmental risk factors using 1319 breast cancer cases and 2094 controls from three case–control studies in Japan. Risk groups were defined based on the number of risk alleles for 14 breast cancer susceptibility loci, namely low (0–10 alleles), moderate (11–16) and high (17+). Environmental risk factors were collected using a self-administered questionnaire and implemented with harmonization. Odds ratio (OR) and C-statistics, calculated using a logistic regression model, were used to evaluate breast cancer susceptibility and model performance. Respective breast cancer ORs in the moderate- and high-risk groups were 1.69 (95% confidence interval, 1.39–2.04) and 3.27 (2.46–4.34) compared with the low-risk group. The C-statistic for the environmental model of 0.616 (0.596–0.636) was significantly improved by combination with the genetic model, to 0.659 (0.640–0.678). This combined genetic and environmental risk model may be suitable for the stratification of individuals by breast cancer risk. New approaches to breast cancer prevention using the model are warranted.

Associations of increasing breast cancer incidence with the current drinking habits and the past smoking habits among Japanese women

“…1 Apart from genetic risk factors, modifiable environmental risk factors for estrogen-related breast cancer such as obesity, alcohol drinking and cigarette smoking, besides reproductive factors, have been evaluated in Japan. 3 The obesity prevalence was not correlated with the breast cancer incidence among Japanese women. 1 The present study aimed to assess associations of the recent increase in breast cancer incidence with the prevalence of obesity and drinking and smoking habits among age-stratified Japanese women, as an ecological study using the national data of Japan.…”

“…1 Apart from genetic risk factors, modifiable environmental risk factors for estrogen-related breast cancer such as obesity, alcohol drinking and cigarette smoking, besides reproductive factors, have been evaluated in Japan. 3 The obesity prevalence was not correlated with the breast cancer incidence among Japanese women. 1…”

CD8+ T cell‑related KCTD5 contributes to malignant progression and unfavorable clinical outcome of patients with triple‑negative breast cancer

“…Breast cancer is caused by unregulated cell proliferation. Breast cancer is the most common cancer in women globally ( 1 ), however, breast cancer can also occur in men. Triple negative breast cancer (TNBC) constitutes 10–20% of all breast cancer cases.…”

Functions of Breast Cancer Predisposition Genes: Implications for Clinical Management

“…Breast cancer (BC) is the most common cancer affecting women globally [1][2][3] and the risk factors for BC include acquired environmental and genetic factors [4][5][6][7]. The main environmental factors include aging, obesity, alcohol consumption, smoking, and an increased exposure to estrogens, such as early menarche, late menopause, late delivery, and postmenopausal hormone replacement therapy combined with estrogen plus progestin.…”