BMC Cancer 2004, 4 http://www.biomedcentral.com/1471-2407/4/9 Table 1: Descriptive characteristics of breast cancer cases (probands) from the US Radiologic Technologist study and their first degree relatives with and without breast cancer. Characteristic at time of interview (1999–2001) Radiologic technologists with breast cancer* (n = 748) First degree female relatives with breast cancer (n = 190) First degree female relatives without breast cancer (N = 2240) N Year of birth <1900 0 1900–29 155 1930–39 202 1940–49 276 1950–59 115 ≥1960+ 0 Calendar year of breast cancer diagnosis <1975 43 1975–79 42 1980–84 98 1985–89 172 1990–94 313 ≥1995 80 Age at diagnosis <40 114 40–49 299 50–59 203 60–69 90 ≥70 42 Relationship to the radiologic technologist (index proband) Mother Sister Daughter % 0.0 20.7 27.0 36.9 15.4 0.0 5.8 5.6 13.1 23.0 41.8 10.7 15.2 40.0 27.1 12.0 5.6 --- --- --- 70 to depict any differences that could be associated with earlier vs. later age-at-onset breast cancer [17].) The vari- ance of the estimated RR was assessed by bootstrap sam- pling of families. The 95% confidence intervals (CI) for the estimated RR were based on the 2.5th and 97.5th per- centiles of the distribution of 1,000 bootstrap replicates of the RR; the p-values for the estimated RR were two-sided and also based on 1,000 bootstrap replications. Adjust- ment for multiple comparisons was performed by either controlling the probability of at least one falsely rejected hypothesis (the so called family-wise error rate [18]) or by controlling the expected proportion of falsely rejected hypotheses among all rejected hypothe- ses (the so called false discovery rate [19]). Results Descriptive characteristics of the radiologic technologists with breast cancer (index probands) and their first degree female relatives (with and without breast cancer) are shown in Table 1. The calendar year of birth and year of breast cancer diagnosis ranges more widely for relatives than for probands because relatives spanned three gener- ations (mother, sister, daughter). Age at first breast cancer diagnosis was higher among relatives as compared to * Includes invasive breast cancer and ductal carcinoma in situ **NA is Not applicable N 19 110 28 20 10 3 56 16 20 35 31 32 22 28 42 49 49 98 85 7 % 10.0 57.9 14.7 10.5 5.3 1.6 29.5 8.4 10.5 18.4 16.3 16.8 11.6 14.7 22.1 25.8 25.8 51.6 44.7 3.7 N 165 702 234 271 304 564 NA** 648 882 710 % 7.4 31.3 10.5 12.1 13.6 25.2 --- --- --- --- --- --- --- --- --- --- --- 28.9 39.4 31.7 probands and reflects the younger ages represented in the cohort. Nearly equal numbers of breast cancers occurred in mothers (98) and sisters (85) with seven breast cancers in daughters. From among 748 radiologic technologists with breast can- cer, 99.6% or more of the samples were successfully gen- otyped (Table 2). Two samples failed repeatedly, leaving 746 consistently genotyped at least 75% of the time. The genotype frequencies for cases are also shown in Table 2. Except for BRCA2 N372H and ZBRK1 1845C>T, all distri- butions were consistent with Hardy Weinberg Equilibrium. Many of the variants analyzed showed no appreciable relationship with breast cancer occurrence (Table 3). However, several variants were associated with increased risk of breast cancer, including XRCC1 R194W (WW or RW vs. RR to age 70; RR = 2.3, 95% CI: 1.3–3.8), XRCC1 R399Q (QQ vs RR to age 50, RR = 3.4; 1.3–9.3), BRIP1 P919S (SS vs PP to age 50; RR = 6.9; 1.6–29.3), and POLD1 R119H (HH or RH vs. RR to age 70, RR = 1.8; 1.0– 2.9). Risks were significantly reduced for APEX D148E heterozygotes (to ages 50 and 70; RR = 0.2; 0.1–0.8 and Page 4 of 12 (page number not for citation purposes)