Registry codes: RSK-BRC-FH · RSK-CRC-FH · converted from the registry dossier families/13-family-history-risks.md — the dossier remains the source of truth; this page is its reading surface.
28 cards · 🟢 8 verified · 🟡 16 qualified · 🔴 4 disputed · ⚪ 0 qualitative — global registry: 41 disputed cards carry their dispute on the card.
Risk ratio by number of affected relatives (mother/sister/daughter): (99% CI 1.69–1.91) · (2.36–3.64) · (2.03–7.49) vs no affected FDR. Mother vs sister did not differ substantially
RR 2.1 (95% CI 2.0–2.2) · Pharoah et al., SR/MA 1997 (74 studies) · Pooling of published summary estimates, mixed designs incl. hospital-based case-control · 1997
Why they differ
طريقة التجميع: تجميع تقديرات منشورة جاهزة (عرضة لانحياز النشر واختلاف التعريفات بين الدراسات) مقابل إعادة تحليل البيانات الفردية بتعريف موحّد وضبط مركزي.
🌐Registry adjudication — original Arabic; English translation pending verification
Adopted
1.80 من إعادة التحليل الفردي — وهي أيضًا الأحدث والأكبر.
🌐Registry adjudication — original Arabic; English translation pending verification
Justification
عند تعارض تجميعين، تتقدّم إعادة تحليل البيانات الخام على تجميع الملخصات؛ والفرق (1.8 مقابل 2.1) لا يغيّر فئة خطر NICE عند أغلب الأنماط، لكن كرت المريض يُبنى على الرقم الأقوى منهجيًا.
🌐Registry adjudication — original Arabic; English translation pending verification
🟡Qualified. Single source, or abstract-level verification — provisional
Applies to — the population, exactly as printed
Age-specific RRs applied to developed-country rates; the paper itself notes the relative's age at diagnosis had only a moderate effect on these cumulative estimates
Sources
Collaborative Group 2001 (abstract-verified)
Grade yourself — spaced repetition
Verification stamp: 🟡 Qualified · Registry audit 2026-11-06 · Pending triple review · Surgery Code registry — family file 13 (13-family-history-risks.md), coded unit; registry audit 2026-11-06. Permalink to this card
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🔴Disputed. Sources disagree — the dispute table is on the card
Applies to — the population, exactly as printed
Prospective cohort, 6,036 BRCA1 carriers (IBCCS/BCFR/kConFab), median follow-up 5 y
Dispute — the sources disagree
To age 70: 40–87% (BRCA1), 27–84% (BRCA2) — ranges across studies · Retrospective literature, as summarised in Kuchenbaecker 2017's Introduction (full text) · Family-based ascertainment through multiple-case cancer families; risks estimated from relatives' genotypes · Retrospective
To age 70: 66% (BRCA1), 61% (BRCA2); to 80: 72% / 69% · Kuchenbaecker 2017, JAMA (PMID 28632866) · Prospective follow-up of 9,856 confirmed carriers; 94% clinic-ascertained, 6% population-based · Median 5 y prospective
Why they differ
التحيّز الانتقائي (ascertainment): العائلات متعددة الإصابات التي بُنيت عليها التقديرات الرجعية تحمل عوامل خطر إضافية (وراثية وبيئية) ترفع التقدير؛ الدراسة الاستشرافية تتابع حاملات مؤكَّدات أيًّا كان تاريخ عائلاتهن — ومع ذلك وجدت أن التاريخ العائلي الأقوى يرفع الخطر داخل الحاملات أنفسهن (RSK-BRC-FH-10)، أي إن جزءًا من «الفرق» حقيقي بيولوجيًا لا منهجيًا فقط.
🌐Registry adjudication — original Arabic; English translation pending verification
Adopted
أرقام Kuchenbaecker الاستشرافية.
🌐Registry adjudication — original Arabic; English translation pending verification
Justification
التصميم الاستشرافي هو الأعلى في التسلسل لهذا السؤال، وهو ما تبنّته الإرشادات اللاحقة (NCI/العيادات) أرقامًا تشغيلية. الرقم «87%» الشائع شعبيًا لا يُطبع إلا داخل هذا الجدول بشرح مصدره.
🌐Registry adjudication — original Arabic; English translation pending verification
🔴Disputed. Sources disagree — the dispute table is on the card
Applies to — the population, exactly as printed
Prospective cohort, 3,820 BRCA2 carriers, same study
Dispute — the sources disagree
To age 70: 40–87% (BRCA1), 27–84% (BRCA2) — ranges across studies · Retrospective literature, as summarised in Kuchenbaecker 2017's Introduction (full text) · Family-based ascertainment through multiple-case cancer families; risks estimated from relatives' genotypes · Retrospective
To age 70: 66% (BRCA1), 61% (BRCA2); to 80: 72% / 69% · Kuchenbaecker 2017, JAMA (PMID 28632866) · Prospective follow-up of 9,856 confirmed carriers; 94% clinic-ascertained, 6% population-based · Median 5 y prospective
Why they differ
التحيّز الانتقائي (ascertainment): العائلات متعددة الإصابات التي بُنيت عليها التقديرات الرجعية تحمل عوامل خطر إضافية (وراثية وبيئية) ترفع التقدير؛ الدراسة الاستشرافية تتابع حاملات مؤكَّدات أيًّا كان تاريخ عائلاتهن — ومع ذلك وجدت أن التاريخ العائلي الأقوى يرفع الخطر داخل الحاملات أنفسهن (RSK-BRC-FH-10)، أي إن جزءًا من «الفرق» حقيقي بيولوجيًا لا منهجيًا فقط.
🌐Registry adjudication — original Arabic; English translation pending verification
Adopted
أرقام Kuchenbaecker الاستشرافية.
🌐Registry adjudication — original Arabic; English translation pending verification
Justification
التصميم الاستشرافي هو الأعلى في التسلسل لهذا السؤال، وهو ما تبنّته الإرشادات اللاحقة (NCI/العيادات) أرقامًا تشغيلية. الرقم «87%» الشائع شعبيًا لا يُطبع إلا داخل هذا الجدول بشرح مصدره.
🌐Registry adjudication — original Arabic; English translation pending verification
Family history modifies risk even within carriers: · 1.99 · 1.91 · 73% vs 53% · 65% vs 39%
≥2 affected 1st/2nd-degree relatives vs none — HR (1.41–2.82) BRCA1, HR (1.08–3.37) BRCA2; cumulative breast risk to age 70 with ≥2 affected relatives vs none: BRCA1 · BRCA2
cumulative breast risk (9–20) by 50 · (26–46) by 70; by family history at age 70: (25–44) with family history → (50–66) with affected at 50. Age-specific RR vs population: 8–9× (<40 y), 6–8× (40–60 y), ~5× (>60 y); male breast cancer RR 8.3
NICE NG164 risk categories (lifetime risk from age 20): near-population <17% · moderate 17–<30% · high ≥30% (risk between ages 40–50: <3% / 3–8% / >8%). NICE states general-population lifetime risk ≈ 11%. Surveillance (no personal history): moderate risk → annual mammography 40–49; high risk (≤30% carrier probability) → annual mammography 40–59; known BRCA1/2 or untested >30% carrier probability → annual MRI 30–49 + annual mammography 40–69. ACS (Saslow 2007): annual MRI in addition to mammography when lifetime risk ≥~20–25% by family-history-based models (BRCAPRO/Claus/Tyrer-Cuzick), for BRCA carriers, and for untested FDRs of carriers; high-risk screening starts at age 30; MRI against at <15% lifetime risk; 15–20% = insufficient evidence
By the relative's age at diagnosis: · <50 y: RR 3.55 · ≥50 y: RR 2.18 · not significant · 3.87
diagnosed (1.84–6.83) · (1.56–3.04) — difference (P=0.19). By the at-risk person's own age: RR 3.17 (2.37–4.25) if the person is <50 vs 1.90 (1.59–2.28) if ≥50 (P=0.003). Johns & Houlston gradient: index <45 y (2.40–6.22) · 45–59 y 2.25 (1.85–2.72) · ≥60 y 1.82 (1.47–2.25)
CRC cumulative incidence to age 75, by gene and sex (PLSD 2023 update — standing set since adjudication 2026-11-08): · 48.3% · 56.0% · 42.6% · 55.8% · 17.3% · 16.4% · 8.5% · 32.8%
MLH1 — F , M · MSH2 — F , M · MSH6 — F , M · PMS2 — F , M (full sex split now published, incl. PMS2). Superseded PLSD 2020 set (n=6,350, with CIs and age-50 detail) preserved in dispute tables B8-i/B8-ii as history only
🔴Disputed. Sources disagree — the dispute table is on the card
Applies to — the population, exactly as printed
Prospective carrier cohorts under colonoscopic surveillance; risks are despite surveillance
Dispute — the sources disagree
MLH1/MSH2: M 27–74%, F 22–61%; MSH6: M 22–69%, F 10–30% · ACG 2015, Table 5 (summarising pre-2015 literature) · Retrospective family studies, mixed eras and ascertainment · «Lifetime», various
MLH1 46% · MSH2 43% · MSH6 15% · PMS2 0% (only 124 PMS2 carriers) · PLSD earlier report (Møller et al.), as tabulated in EHTG/ESCP Mallorca guideline 2021, Table 3 · Prospective, n=3,119, both sexes combined · To age 75
MLH1 F 48.3 / M 57.1 · MSH2 F 46.6 / M 51.4 · MSH6 F 20.3 / M 18.2 · PMS2 10.4 · PLSD 2020 (Dominguez-Valentin, Genet Med, PMID 31337882), Table 1 · Prospective, n=6,350, validated + original cohorts merged, sex-specific · To age 75
PMS2 sub-dispute — M/F 12% (Table 5 aggregate); single study of 99 carriers: 15–20% by age 70 · ACG 2015 (citing Senter et al. 2008) · Retrospective carrier series
PMS2 sub-dispute — 10.4% (2.9–40.8) to 75; no CRC before age 50; risk «not significantly increased» overall in the paper's own conclusion · PLSD 2020 · n=407 PMS2 carriers, prospective
Why they differ
ثلاثة أسباب موثقة: (١) الانتقاء الرجعي من عائلات شديدة الإصابة يضخّم الطرف الأعلى (74%)؛ (٢) الأترابيات الاستشرافية تحت مراقبة منظارية — أرقامها «خطر رغم المراقبة» لا خطرًا طبيعيًا؛ (٣) PMS2 كان هزيل الأعداد في التقرير الأسبق (124 حاملًا، صفر حدث) فجاءت نقطته 0% خادعة، واتسعت في 2020 إلى 10.4% بفاصل ثقة واسع جدًا (2.9–40.8).
🌐Registry adjudication — original Arabic; English translation pending verification
Adopted
PLSD 2020 مفصّلًا بالجين والجنس.
🌐Registry adjudication — original Arabic; English translation pending verification
Justification
أكبر أترابية استشرافية مُتحقَّق منها بأترابية تحقق مستقلة قبل الدمج؛ وهي المرجع الذي بنت عليه إرشادات Mallorca الجينية اللاحقة جداولها. [مُبدَّل في شقّ العرض — 2026-11-08: صارت أرقام PLSD 2023 هي العرض القائم (انظر «تحكيم لاحق — 2026-11-08» بعد B8-ii)؛ هذا النص وجدول المصادر أعلاه باقيان حرفيًا كتاريخ خلاف.]
🌐Registry adjudication — original Arabic; English translation pending verification
Sources
Dominguez-Valentin et al. (PLSD), EClinicalMedicine 2023;58:101909 — Table «Lifetime cancer risk related to Lynch genotypes» as reproduced in UpToDate (checked 2026-11-08) — dispute tables B8-i/B8-ii + تحكيم لاحق 2026-11-08
Grade yourself — spaced repetition
Verification stamp: 🔴 Disputed · Registry audit 2026-11-06 · Pending triple review · Surgery Code registry — family file 13 (13-family-history-risks.md), coded unit; registry audit 2026-11-06. Permalink to this card
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Endometrial cancer cumulative incidence to age 75 (PLSD 2023 update — standing set since Tamer's decision 2026-11-09, unifying with FH-08): · 37.2% · 44.1% · 45.7% · 21.2%
MLH1 · MSH2 · MSH6 · PMS2 — in women, gynaecological cancers rival or exceed CRC in MSH2/MSH6/PMS2 carriers. Superseded PLSD 2020 set (37.0 / 48.9 / 41.1 / 12.8) preserved in the registry's B8 adjudication note of 2026-11-09 as history only
Surveillance works (historical controlled cohort): · 62% reduction in CRC incidence · 65% less CRC death
colonoscopic surveillance in Lynch families — and (P=0.003) vs those who declined surveillance (Järvinen programme, as summarised and tabulated by ACG)
~100% · 38–41 years · 39 years (range 34–43) · 69%
Untreated classic FAP: CRC risk ; average age at CRC (guideline table); GeneReviews-derived mean age ; ~95% have polyps by age 35. Attenuated FAP: CRC risk , average age 54–58
ACG CRC Screening 2021 (family-history arm): 1 FDR with CRC or advanced adenoma diagnosed <60 y, or ≥2 FDRs at any age → colonoscopy at age 40 or 10 years before the youngest case, whichever is earlier, repeated every 5 years. 1 FDR diagnosed ≥60 y → start screening at 40 (any modality), then average-risk intervals if normal. Only 1 second-degree relative → average-risk screening. (US Multi-Society Task Force position is concordant.)
Lynch surveillance (ACG Hereditary 2015): colonoscopy at least every 2 years beginning age 20–25; annual colonoscopy should be considered in confirmed carriers; for MSH6/PMS2 carriers, starting at 25–30 may be considered unless an early-onset family cancer dictates earlier
FAP surveillance (ACG Hereditary 2015): annual colonoscopy or flexible sigmoidoscopy beginning at puberty for at-risk/affected individuals in classic FAP families; absolute colectomy indications = documented/suspected cancer or significant symptoms