There is 2 patient that did not consent and removed.

Note: Of 1256 total survey respondents, 847 had complete data on 12 key variables (Consent, received germline genetic testing, genetic diagnosis, age at diagnosis (germline mutation), genetic test result, sex at birth, age range, cancer diagnosis, family history of stomach cancer, any gastric lesion, race/ethnicity, anti-acid medication/proton pump inhibitors). We proceed our analysis with n=847 patients.

Figures

Self-reported cancer diagnosis. Note patients may indicate more than one cancer.

Self-reported race/ethnicity. Note patients may report more than one race/ethnicity.

Self-reported genes. Note patients may report more than one gene.

Self-reported genes among Stomach cancer patients. Note patients may report more than one gene.

Self-reported gastric lesions. Note patients may report more than one lesion.

Table 1. Overall demographics and health characteristics

Characteristic N = 8471
Age
    Less than 29 15 (1.8%)
    30-39 88 (10%)
    40-49 202 (24%)
    50-59 202 (24%)
    60-69 212 (25%)
    70 and over 128 (15%)
Sex
    Female 803 (95%)
    Male 44 (5.2%)
Race_Ethnicity
    American Indian, Alaska Native, or First Nations 1 (0.1%)
    Asian or Asian American 13 (1.5%)
    Black or African-American 4 (0.5%)
    Hispanic White 10 (1.2%)
    Hispanic, Latino, or Latinx 29 (3.4%)
    Mixed race/ethnicity 12 (1.4%)
    Non-Hispanic White 771 (91%)
    Other 7 (0.8%)
Any_Gastric_Lesion 422 (50%)
H_pylori 55 (6.5%)
Fam_Hist_Stomach_Cancer
    Don't know 145 (17%)
    No 488 (58%)
    Yes 214 (25%)
Stomach_Cancer 35 (4.1%)
1 n (%)

Table 2. Risk factors by any gastric lesion

Any grastric lesion includes any of the following:

  1. Helicobacter Pylori (H. pylori)

  2. Gastritis

  3. Gastric Ulcer

  4. Gastro-esophageal reflux (GERD)

  5. Intestinal Metaplasia

  6. Barrett’s Esophagus

  7. Pernicious Anemia

HR genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, PALB2, RAD51C, RAD51D, NBN

Lynch genes: MLH1, MSH2, MSH6, PMS2, EPCAM

Hereditary Diffuse Gastric Cancer (HDGC) genes: CDH1, CTNNA1

Juvenile Polyposis Syndrome genes: SMAD4, BMPR1A

Peutz-Jeghers Syndrome gene: STK11 (also known as LKB1)

Li-Fraumeni Syndrome gene: TP53

Recessive cancer predisposition syndrome genes: MUTYH, NTHL1

All other genes not included: CDKN2A, ENG, NF1, PTEN

Table 3. Risk factors by H. pylori status

Table 4. Cancers by family history of gastric cancer

Note: n=145 who responded “Don’t know” are not included in table 4.

Table 5. Risk factors by gastric cancer status

Characteristic Overall
N = 409
1
No
N = 374
1
Yes
N = 35
1
p-value
Fam_Hist_Stomach_Cancer


0.0382
    Don't know 64 (16%) 58 (16%) 6 (17%)
    No 239 (58%) 225 (60%) 14 (40%)
    Yes 106 (26%) 91 (24%) 15 (43%)
Any_Gastric_Lesion


0.0042
    No 200 (49%) 191 (51%) 9 (26%)
    Yes 209 (51%) 183 (49%) 26 (74%)
H_pylori


0.0033
    No 384 (94%) 356 (95%) 28 (80%)
    Yes 25 (6.1%) 18 (4.8%) 7 (20%)
HR


<0.0012
    No 94 (23%) 76 (20%) 18 (51%)
    Yes 315 (77%) 298 (80%) 17 (49%)
Lynch


0.82
    No 343 (84%) 313 (84%) 30 (86%)
    Yes 66 (16%) 61 (16%) 5 (14%)
HDGC


<0.0013
    No 387 (95%) 362 (97%) 25 (71%)
    Yes 22 (5.4%) 12 (3.2%) 10 (29%)
Anti_acid_ever


0.62
    No 168 (41%) 155 (41%) 13 (37%)
    Yes 241 (59%) 219 (59%) 22 (63%)
Anti_acid_time


0.0013
    No 168 (41%) 155 (41%) 13 (38%)
    Daily 105 (26%) 88 (24%) 17 (50%)
    1-4 times weekly 57 (14%) 57 (15%) 0 (0%)
    1-4 times monthly 21 (5.1%) 20 (5.3%) 1 (2.9%)
    1-4 times in past 6 months 48 (12%) 47 (13%) 1 (2.9%)
    Other/As needed 9 (2.2%) 7 (1.9%) 2 (5.9%)
    Missing 1 0 1
1 n (%)
2 Pearson’s Chi-squared test
3 Fisher’s exact test

Let’s look at cell counts for (gastic cancer/no cancer), H pylori, and HR

##                              HR  No Yes
## Stomach_ORNO_Cancer H_pylori           
## No                  No           75 281
##                     Yes           1  17
## Yes                 No           15  13
##                     Yes           3   4

Table 6. Risk factors by (gastric cancer or any gastric lesion)

Cases: Gastric cancer, or any gastric lesion

Controls: (Non-gastric cancer and no family history of gastric cancer) or no cancer

Note we are assuming comparability of groups.

Characteristic Overall
N = 622
1
0
N = 191
1
1
N = 431
1
p-value
H_pylori


<0.0012
    No 567 (91%) 191 (100%) 376 (87%)
    Yes 55 (8.8%) 0 (0%) 55 (13%)
Anti_acid_ever


<0.0012
    No 217 (35%) 118 (62%) 99 (23%)
    Yes 405 (65%) 73 (38%) 332 (77%)
HR


0.0232
    No 147 (24%) 34 (18%) 113 (26%)
    Yes 475 (76%) 157 (82%) 318 (74%)
Lynch


0.0892
    No 506 (81%) 163 (85%) 343 (80%)
    Yes 116 (19%) 28 (15%) 88 (20%)
HDGC


0.22
    No 595 (96%) 186 (97%) 409 (95%)
    Yes 27 (4.3%) 5 (2.6%) 22 (5.1%)
FAP


0.23
    No 609 (98%) 185 (97%) 424 (98%)
    Yes 13 (2.1%) 6 (3.1%) 7 (1.6%)
Juvenile_Polyposis_Syndrome


>0.93
    No 621 (100%) 191 (100%) 430 (100%)
    Yes 1 (0.2%) 0 (0%) 1 (0.2%)
Peutz_Jeghers_Syndrome


>0.93
    No 620 (100%) 191 (100%) 429 (100%)
    Yes 2 (0.3%) 0 (0%) 2 (0.5%)
Li_Fraumeni_Syndrome


0.33
    No 618 (99%) 191 (100%) 427 (99%)
    Yes 4 (0.6%) 0 (0%) 4 (0.9%)
Recessive_Cancer_Predisposition


0.73
    No 612 (98%) 189 (99%) 423 (98%)
    Yes 10 (1.6%) 2 (1.0%) 8 (1.9%)
Stomach_Genes


0.22
    No 17 (2.7%) 3 (1.6%) 14 (3.2%)
    Yes 605 (97%) 188 (98%) 417 (97%)
Other_genes



    No 622 (100%) 191 (100%) 431 (100%)
1 n (%)
2 Pearson’s Chi-squared test
3 Fisher’s exact test

Table 7. Associations between cancer-predisposing gene groups and risk for (gastric cancer or any gastric lesion).

Models are adjusted for sex and current age category. 95% CI uses the profile likelihood method.

Gene No cancer/Non-gastric cancer & No family history n=191 Gastric/Lesion n=431 OR (95% CI) P-Value
HRYes 157 (82.2) 318 (73.78) 0.51 (0.32-0.79) 0.0032270
LynchYes 28 (14.66) 88 (20.42) 1.7 (1.06-2.81) 0.0318357
HDGCYes 5 (2.62) 22 (5.1) 2.22 (0.87-6.86) 0.1229374
FAPYes 6 (3.14) 7 (1.62) 0.59 (0.19-1.89) 0.3581004
Recessive_Cancer_PredispositionYes 2 (1.05) 8 (1.86) 1.36 (0.32-9.35) 0.7037720
Stomach_GenesYes 188 (98.43) 417 (96.75) 0.44 (0.1-1.4) 0.2082300
BRCA1Yes 39 (20.42) 75 (17.4) 0.78 (0.5-1.23) 0.2745887
BRCA2Yes 72 (37.7) 111 (25.75) 0.55 (0.38-0.81) 0.0020614
CDH1Yes 5 (2.62) 21 (4.87) 2.1 (0.81-6.5) 0.1544493
H_pyloriYes 0 (0) 55 (12.76) 20155697.5 (0.03-2.40374308521098e+83) 0.9735432

Interaction effects - (Unable to do, 0 cell)

Parameter Odds Ratio SE 95% CI z p
HR (Yes) 0.46 0.11 (0.29, 0.72) -3.35 < .001
H pylori (Yes) 1.21e+07 1.57e+10 (0.00, Inf) 0.01 0.990
HR (Yes) × H pylori (Yes) 2.00 2827.38 (0.00, Inf) 4.91e-04 > .999

Table 8. Stomach Cancer: Interaction effects of HR and HDGC genes with H. pylori any gastric lesion

Models adjusted for sex and entry age category. 95% CI uses the profile likelihood method. Note that interaction analysis is likely underpowered due to low n=35 stomach cases.

8a. HR x H. pylori

##              Stomach_ORNO_Cancer  No Yes
## HR  H_pylori                            
## No  No                            75  15
##     Yes                            1   3
## Yes No                           281  13
##     Yes                           17   4
Parameter Odds Ratio SE 95% CI z p
HR (Yes) 0.21 0.09 (0.09, 0.48) -3.73 < .001
H pylori (Yes) 23.01 31.78 (2.03, 742.03) 2.27 0.023
HR (Yes) × H pylori (Yes) 0.21 0.32 (5.38e-03, 3.22) -1.02 0.306

8b. HR x any gastric lesion

##                        Stomach_ORNO_Cancer  No Yes
## HR  Any_Gastric_Lesion                            
## No  No                                      34   5
##     Yes                                     42  13
## Yes No                                     157   4
##     Yes                                    141  13
Parameter Odds Ratio SE 95% CI z p
HR (Yes) 0.18 0.13 (0.04, 0.74) -2.40 0.016
Any Gastric Lesion (Yes) 2.28 1.40 (0.72, 8.27) 1.35 0.178
HR (Yes) × Any Gastric Lesion (Yes) 1.50 1.28 (0.28, 8.31) 0.48 0.630

8c. HDGC x H. pylori

##               Stomach_ORNO_Cancer  No Yes
## HDGC H_pylori                            
## No   No                           344  19
##      Yes                           18   6
## Yes  No                            12   9
##      Yes                            0   1
Parameter Odds Ratio SE 95% CI z p
HDGC (Yes) 22.85 13.62 (7.23, 77.23) 5.25 < .001
H pylori (Yes) 5.14 2.88 (1.60, 14.92) 2.92 0.004
HDGC (Yes) × H pylori (Yes) 7.35e+14 4.85e+18 (0.00, ) 5.19e-03 0.996

8d. HDGC x any gastric lesion

##                         Stomach_ORNO_Cancer  No Yes
## HDGC Any_Gastric_Lesion                            
## No   No                                     186   5
##      Yes                                    176  20
## Yes  No                                       5   4
##      Yes                                      7   6
Parameter Odds Ratio SE 95% CI z p
HDGC (Yes) 49.76 46.31 (8.30, 350.64) 4.20 < .001
Any Gastric Lesion (Yes) 4.25 2.21 (1.65, 13.16) 2.78 0.005
HDGC (Yes) × Any Gastric Lesion (Yes) 0.24 0.27 (0.02, 2.21) -1.25 0.210

Table 9. Colorectal Cancer: Interaction effects of HR and Lynch genes with H. pylori

Models adjusted for sex and entry age category. 95% CI uses the profile likelihood method. Note that interaction analysis is likely underpowered due to low n=36 colorectal cases. There are cells with 0 value.

9a. HR x H. pylori

## , ,  = No
## 
##      
##        No Yes
##   No  151   8
##   Yes 607  45
## 
## , ,  = Yes
## 
##      
##        No Yes
##   No   27   0
##   Yes   7   2
Parameter Odds Ratio SE 95% CI z p
HR (Yes) 0.05 0.02 (0.02, 0.12) -6.61 < .001
H pylori (Yes) 8.89e-08 1.22e-04 (, 1.69e+43) -0.01 0.991
HR (Yes) × H pylori (Yes) 4.28e+07 5.87e+10 (8.86e-22, 1.14e+186) 0.01 0.990

9b. Lynch x H. pylori

## , ,  = No
## 
##      
##        No Yes
##   No  638  48
##   Yes 120   5
## 
## , ,  = Yes
## 
##      
##        No Yes
##   No    9   1
##   Yes  25   1
Parameter Odds Ratio SE 95% CI z p
Lynch (Yes) 17.03 7.08 (7.83, 40.63) 6.82 < .001
H pylori (Yes) 1.44 1.54 (0.19, 7.99) 0.34 0.734
Lynch (Yes) × H pylori (Yes) 0.53 0.83 (0.04, 16.59) -0.41 0.684
##                                                  H_pylori  No Yes
## Race_Ethnicity                                                   
## American Indian, Alaska Native, or First Nations            1   0
## Asian or Asian American                                    11   2
## Black or African-American                                   4   0
## Hispanic White                                             10   0
## Hispanic, Latino, or Latinx                                20   9
## Mixed race/ethnicity                                        9   3
## Non-Hispanic White                                        730  41
## Other                                                       7   0

Locations of the 41 NHWs that have H. pylori

## 
##          California            Colorado         Connecticut             Florida 
##                   2                   1                   1                   3 
##           Isla Wake              Kansas            Kentucky               Maine 
##                   1                   1                   1                   2 
##            Missouri             Montana       New Hampshire          New Jersey 
##                   1                   1                   1                   1 
##            New York      North Carolina                Ohio              Oregon 
##                   2                   5                   2                   2 
## Prefer not to share               Texas                Utah            Virginia 
##                   3                   3                   1                   1 
##          Washington       West Virginia           Wisconsin 
##                   4                   1                   1