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Gansu Wuwei Tumor Hospital. Wuwei 733000 Gansu Province, China.
Correspondence to: Professor Deng-Hai Mi, Gansu Wuwei Tumor Hospital.Wuwei 733000 Gansu Province, China. midenghai@163.com cxp197233@sina.com Telephone: 86 931-2268006
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ABSTRACT |
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INTRODUCTION |
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MATERIALSANDMETHODS |
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RESULTS |
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DISSCUSSION |
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ABSTRACT
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AIM: To explore hereditability of gastric cancer in Wuwei city. METHODS: A case-control study was used to investigate 251 gastric cancer families located in Wuwei city. Li-Mantel-Gan and Falconer regression methods were used to calculate segregation ratios and hereditability. RESULTS: The segregation ratio in Wuwei families was 0.0774, the hereditability of class I kinfolks and class II kinfolks were respectively 22.91% and 20.07%. CONCLUSION: The segregation ratio of gastric cancer in Wuwei was significantly lower than for mono-genetic diseases (0.25), corresponding better with a model of polygenetic diseases. The genetic susceptibility factor accounted for about 1/5-1/4 in the formation of gastric cancer familial aggregation. Mi DH, Chen XP, Luo HZ Research on hereditability of gastric cancer in Wuwei city.
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INTRODUCTION |
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Wuwei city locates on Gansu Hexi hallway, where its total area is more
than 6000 sq. km and its infield area is over 1300 thousand acres. The height of
west of Wuwei is from1800 to 2400 meters above sea level where is an area with
farming and herd. The middle part of Wuwei, 1500 to 1800 meters above sea level,
is cropper area where it abounds in wheat, rice, corn and yam. East of Wuwei
abuts on Tenggeli bigdesert. There are some rivers like Zhamu river, Huangyang
river, Jinta river and Xiying river about which its region are all from Qilianin
mountain. Total rainfall is about 160 mm and total evaporation is about 2100 mm
yearly. Temperature in Wuwei is big difference from seasons, from average
-15.40C in January to 29.10C in July. The population is about 1000 thousand
individual. Mean expectation life-span is 69.07 for man and 68.23 for female in
the year 2000. Agriculture population accounts for 83%. There are multi-ethnarch
in Wuwei including Han, Man, Hui, Zang, Tu and Weiwuer. Economic level of
residents is mostly based on agriculture income. The mean income is about 3000
Yuan a year per people.
The higher occurrence area of gastric cancer is in Wuwei city in northwest of
China. Its incidence of gastric cancer was 91.18/100,000 from 2001 to 2002.
Prevalent danger factor of Wuwei city from various aspects were studied
including environment, biology, chemistry factors like meal, nutrition and
nitrosamine content in pickle vegetable. The occurrence and development of
gastric cancer might be the results of the environment factor and the host
factor interaction. The former researches expressed that it involves the
mutation of several oncogenes and anti-oncogenes in the process of the
occurrence and development of the gastric cancer. In recent years, it has
already obtained some certain achievement to the research on hereditary gastric
cancer. [1-4] But it needs more studies to finally clarify about prevalent
factor of occurrence and death of gastric cancer for Wuwei city, we investigated
251 gastric cancer families from January 2002 to April 2003 in order to open out
the heredity pattern and regulations of gastric cancer of the high occurrence
region in Wuwei city. The results were reported as follows.
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MATERIALS AND METHODS
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Making sure the core family of gastric
cancer proband
Two hundreds and fifty-one gastric cancer probands were from surgical inpatients
in Wuwei native place between January 2002 and April 2003. There were 189 male
cases and 62 female cases. If a family had 2 cases or more than 2 cases of
gastric cancer patients, the recently serious case was taken as proband and core
family. The 251 control core families were selected from close neighbors who had
no blood relationship with probands.
Investigation methods
With the specially made inquisition form, the specialized training medical
personnels visited probands and the control core families who were made the core
to home. It was particularly investigated for their kinfolks of three class
(class I, class II and class III), two lines (the patriline and the matriline)
and four generations (previous two generation, contemporary and next
generation). Class I kinfolks included parent, brethren and family. Class II
kinfolks included the grandparents, uncle and aunt. Class III kinfolks included
cousin. The investigated contents included general circumstance and case history
of gastric cancer.
Statistics methods
Adopt Li-Mantel-Cart method to estimate the segregation ratio (P) of gastric
cancer
Segregation ratio: P=（R-J）/（T-J）
Variance of segregation ratio: SP2=（R-J）（T-R）/（T-J）3
Standard error: SEP=（SP2）1/2
95% confidence interval: P±1.96SEP
T: the total number of brethren R: the total number of sufferer in brethren J:
the core family number of only 1 sufferer in brethren
Adopt Falconer regression method to estimate hereditability
Hereditability: h2=b / r
Regression coefficient: b= (1-qc) (xc-xr)/ac
Variance: Vb= ( 1/ac2 ) (qr/ar2A)
Standard error: Sh=Vb1/2/r
95% confidence interval: h2±1.96sh
r: relative coefficient xc: difference of susceptibility average and threshold
value of proband cases xr: difference of susceptibility average and threshold
value of control kinfolks a: ratio of threshold value probability density and
morbidity of general crowd qr: morbidity of proband cases qc: morbidity of
control kinfolks A: absolute number of proband case kinfolk sufferers
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RESULTS |
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To estimate segregation ratio of gastric cancer
According to the characteristic of case origin and its family, it is
listed at table 1 for distributing of gastric cancer in brethren, and
the segregation ratio was estimated. The result revealed that the
segregation ratio of Wuwei gastric cancer was 0.0774 and obviously less
than 0.25. And its standard error was 0.00006992, 95% confidence
interval 0.0609~0.0939. The morbidity of gastric cancer in brethren was
far under 1/4 and had significantly difference for that of mono-gene
hereditary disease which was less that of dominant inheritance. It was
also the same as recessive inheritance. Therefore Wuwei gastric cancer
could be polygene hereditary pattern.
To estimate hereditary degree
Hereditability of gastric cancer was listed at table 2 for in Wuwei city. It was
obvious that hereditability of gastric cancer class I kinfolks was 22.91%, male
was 22.84% and female was 21.02%, and that of class II kinfolks was 20.07%, male
was 26.52%, female was 16.24%. Thus it could be seen that the genetic factor had
certain pathogenic function in the outbreak of the gastric cancer.
Gastric cancer family history
It was 20.32%（51/251）that there was gastric cancer family history among probands
in case group, and was 9.52%（20/251）in control group, χ2=15.99 and P＜0.01 by χ2
test. Considering relative fatalness, class I kinfolks proband was 1.91 times of
control, class II kinfolks was 1.47 times of control. χ2=11.64 and P＜0.01 of
gastric cancer prevalence rate of class I kinfolks by χ2 test, and χ2=1.99 and
P＞0.05 of that of class II kinfolks by χ2 test that gastric cancer prevalence
rate of proband group was higher than that of control group but had not
statistics significance. There were 30 ancestry and its ratio was
58.82%（30/51）that gastric cancer patient were more than 3 cases among probands
whose family had gastric cancer family history, among there were 25 ancestry and
its ratio was 49.02%（25/51）that 1 case was the first kinfolk of other 2 cases,
there were 15 cases whose the taken bad age was less than 45.
Being compared segregation ratio and hereditability of gastric cancer with
different high occurrence region.
It was listed at table 3 for segregation ratio and hereditability of gastric
cancer at different high occurring region.
| DISCUSSIONS
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It involves the mutation of several oncogenes and antioncogenes in the
process of occurrence and development of gastric cancer. In recent years, by the
study on hereditary large intestine cancer, Li-Fraumeni symptom and hereditary
mammary cancer, ovarian cancer symptom etc. It has been used for reference and
promoting function to the study on family gastric cancer. Wuwei city is the high
occurrence region of gastric cancer, year incidence rate is more than
59.29/100,000. This has been proved up that gastric cancer has hereditary
susceptibility essence and this also makes a reasonable explanation of
prevalence character of gastric cancer. By case-control study on gastric cancer,
it was found that gastric cancer sufferer who had family history was 20.32% in
Wuwei city, prevalence rate of proband gastric cancer was 1.91 times higher than
control group. This would indicate that occurrence of gastric cancer had family
aggregation character in Wuwei city and that also was found in Yangzhong &
Jintan & Taixing of Jiangsu province and Dalian of Liaoling province in the
investigation on gastric cancer hereditary factor. Videback and Mosbech found
that gastric cancer morbidity that had gastric cancer family history was 4 times
of that without family history by follow-up surveying 302 family numbers of
gastric cancer sufferer. [5] It indicated that hereditary factor had important
effect in the process of family gastric cancer occurrence. Hereditary gastric
cancer of international collaboration study group (ICG-HGC) constituted
diagnostic standard of ICG- HGC about hereditary gastric cancer: [6] there were
at least 3 cases who were made sure gastric cancer in a ancestry, among 1 case
must be the first kinfolk of other 2 cases, and at least consecutive two
generation who suffered from gastric cancer, and at least 1 case whose taken bad
age was less than 45. By case-control study on gastric cancer in Wuwei city, it
was found 30 ancestries had more than 3 cases gastric cancer, among there were
25 ancestries that 1 case was the first kinfolk of other 2 cases, there were 15
cases whose taken bad age was less than 45, these character were similar with
HNPCC.
Hereditary disease may be divided into mono-gene and polygene. According to
disease colony genetics data of domestic and international in existence, it
should be less than 0.25 for segregation ratio of polygene hereditary disease.
Segregation ratio of Wuei gastric cancer was 0.0774, its hereditary pattern fall
short of mono-gene hereditary rule and was polygene hereditary pattern that
several genes that had minuteness effect came into being total effect and at
last occurred gastric cancer at action of certain environment factors (including
carcinogenic epiphyte and nitrosamine in food, chemistry carcinogen,
inconsequence meal frame, fruit and truck incepting lack and being short of
vitamin C, et al. [7]). Generally character of polygene hereditary disease were
that the difference of prevalence rate of colony and class I kinfolks related
with hereditability, prevalence rate of class I kinfolks was bigger than that of
class II kinfolks and that of class II kinfolks was bigger than that of colony.
At the data of this text report, prevalence rate of class I kinfolks was 3.15%,
class II kinfolks was 1.34%, colony was 1.28%, these accorded with the character
of polygene hereditary disease.
Hereditability of class I kinfolks that was estimated at this study was 22.91% ,
and was similar with that being reported by Wu jian-zhong and Sheng jin [1-2],
it showed that hereditary factor reacted certainly and about accounted
for1/5~1/4 with whole dangerous factor. Whole kin kinfolks of gastric cancer
patient may be regarded as being exposed to double influence of hereditary and
environment factor, non-kin kinfolk only was exposed to influence of environment
factor. Considering hereditary degree of polygene hereditary disease, it was
accepted at present that that was counted according to Falconer,s threshold
value theory. Though the influence of environment factor farrago could not
completely be excluded, at this study, control group was the same as village,
nation, gender, similar with age, and without kin of three generations with
proband, the influence of non- hereditary factor was furthest excluded, they
made the result accord with fact.
Summarizing above-mentioned discussion, the research on gastric cancer
hereditability from macroscopical hereditary epidemiology should distinguish kin
and habitation with the influence of gastric cancer. Further considerations are
that kin included having blood relationship and common living, having blood
relationship and without common living, without blood relationship and having
common living. Meanwhile it should open out the occurrence and development of
gastric cancer from the molecular biology level and provide scientific gist for
etiology prevention of gastric cancer.
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REFERENCES
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