Constitutional Oncogenetics. Noureddine Boukhatem

of their presence is the primary reason for oncogenetic consultations. Genetic alterations predisposing to these two syndromes identified in index patients and their relatives in 2016 in France represented 67% of all genetic predispositions to cancer (breast/ovary 53% and Lynch 14%). We then deal with the other syndromes for which the percentage of genetic alterations identified as predisposing them is greater than 1%. In Part 2, we describe the syndromes for which the percentage of genetic alterations predisposing them is less than 1%.

DEFINITION.– The term index case (patient zero) is used to refer to the first person in an outbreak to have been infected with a pathogen. Here, the index case or index patient is the first person in a family where a genetic abnormality (mutation in the broadest sense) has been detected.

      DEFINITION.– The term relative refers to a person who has a family (blood) relation to the index case.

      DEFINITION.– The term syndrome refers to a group of several symptoms characteristic of a specific disease, constituting a recognizable clinical entity and attributable to a certain cause.

      DEFINITION.– The term genetic predisposition refers to an increased likelihood or probability of developing a particular disease due to the presence of one or more mutations in the gene and/or a family history indicating an increased risk of the disease. It is also known as genetic susceptibility.

In this book, we consider the syndromes of genetic predisposition to cancers that were diagnosed in France in 2016 (see Table I.1). These syndromes are classified here (see Table I.2) according to statistics on index patients and their relatives carrying a genetic alteration predisposing to cancer, identified in the various accredited centers in France in 2016.

The national organization of oncogenetics in France, under the aegis of the INCa, is a unique and efficient model enabling complete care of the families concerned. Figure I.1, reproduced from the INCa report cited above, gives a summary of the path of index patients and their relatives through the oncogenetic circuit.

Table I.1 Statistics on index patients and their relatives carrying a genetic alteration predisposing to cancer, identified in in 2016 by the various accredited centers in France

Predispositions	Genes	AR	IC+	REL+	Total
Breast ovarian syndrome (including isolated ovarian cancers)	BRCA1	/	893	1,280	4,356
	BRCA2	/	777	1,165
	PALB2	/	64	51
	RAD51	/	16	8
	Other	/	12	0
Lynch syndrome	MLH1	/	128	203	1,148
	MSH2	/	163	236
	MSH6	/	116	134
	PMS2	/	54	93
	EPCAM	/	6	10
	Other*	/	1	4
	APC	/	128	148
Familial adenomatous polyposis	MUTYH	BI	64	20	528
		MONO	72	86
	POLE	/	4	4
	POLD1	/	1	0
	NTHL1	BI	1	0
		MONO	0	0
Hereditary diffuse gastric cancer	CDH1	/	11	36	47
Endocrine neoplasia	MEN1	/	45	61	213
	RET	/	40	64
	CDKN1B	/	3	0
Von Hippel–Lindau syndrome	VHL	/	28	17	45
Hereditary paraganglioma– pheochromocytoma	SDH Скачать книгу В начало < 2 3 4 5 6 7 8 9 10 11 > В конец