TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

Abstract

Two common variants in transforming growth factor-b receptor 1 (TGFBR1), TGFBR1*6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n ¼ 459) and in breast cancer patients from a familial cancer clinic (n ¼ 340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high-and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1*6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P ¼ 0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P ¼ 0.83 and 0.83, respectively). TGFBR1*6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01 -5.11; P ¼ 0.049). These results indicate that the TGFBR1*6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material.

The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer

“…The three studies [4,9,13] ( Table 3) that selected patients on the basis of family history, young age or bilaterality showed a trend towards a positive association, although only the study by Baxter et al [4] (355 cases) reached significance. However, subgroup analysis of the study by Song et al [9] did show a borderline significant association in patients with 'low-risk familial' breast cancer (one first degree relative or second degree relative).…”

“…However, subgroup analysis of the study by Song et al [9] did show a borderline significant association in patients with 'low-risk familial' breast cancer (one first degree relative or second degree relative). The Polish familial study [13] In studies where cases were unselected, the studies showing a trend towards a positive association were from the USA and predominantly Caucasian cohorts [3,14,15].…”

“…A meta-analysis including this data and previously published data also showed no association (OR 1.10, 95% CI 0.89-1.38). Subsequently, a Swedish group [9] analysed their cohort of breast cancer cases (763 cases, 852 controls) and although they found no overall association, they did find a weak association with low-risk familial breast cancer and poorly differentiated breast cancer.…”

BRCA1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms

“…The cutpoints used were described earlier and provided the categories \28/\28?\28/C28 and C28/C28 for AIB1 28824 (CAG/CAA)n [34][35][36][37], C29/C29?C29/\29 and \29/\29 for AR 171(CAG)n [38,39], \10/\10, \10/C10 and C10/ C10 for CYP19A1 15210(TTTA)n [9], 3/3, 2/2 and 2/3?2/4 for TYMS -97(28)n [11] and 6/6?6/9 and 9/9?9/10 for TGFBR1 52(GCG)n [32]. For XRCC3 204(GT)n, cutpoint 14 was selected using maximal selected rank statistics [47], yielding the categories B14/B14, B14/ [14 and [14/[14. For CYP11A1 (AAAAT)n, the categories were 4/4, 4/6, 6/6, 8/any and others [26].…”

Role of Transforming Growth Factor Receptor B I Type (Tgf-Bri) in the Progression of the Luminal Breast Cancer Subtype

“…Существует ряд работ, посвященных изучению полиморфизма гена TGF-βR1 (rs334354), однако представлены результаты исследования только его рисковой значимости, которые получены для общей выборки больных РМЖ без сопоставления с молекулярными подтипами. Так, в работе Song et al не выявлено ассоциаций между мутантным аллелем Int7G24A и риском развития РМЖ [16]. Более ранние опубликованные данные указывают на взаимосвязь носительства данного полиморф-ного варианта с инвазивным и метастатическим РМЖ [13].…”